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Sample records for curcumin nanoparticles inhibit

  1. Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection

    NASA Astrophysics Data System (ADS)

    Yang, Xiao Xi; Li, Chun Mei; Huang, Cheng Zhi

    2016-01-01

    Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concentration of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV.Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition

  2. Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection.

    PubMed

    Yang, Xiao Xi; Li, Chun Mei; Huang, Cheng Zhi

    2016-02-01

    Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concentration of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV. PMID:26781043

  3. Upconversion nanoparticles conjugated with curcumin as a photosensitizer to inhibit methicillin-resistant Staphylococcus aureus in lung under near infrared light

    PubMed Central

    Ye, Yong; Li, Yue; Fang, Fei

    2014-01-01

    Curcumin has phototoxic effects on bacteria under <450 nm irradiation, but it is unstable in vivo and cannot exert effects on deep tissues. Near infrared light (NIR) is harmless to the body and has stronger penetration than visible light. In order to improve the effects of curcumin, upconversion nanoparticles conjugated with curcumin (UCNPs-curcumin) are designed to upconvert NIR to the excitation wavelength of curcumin. UCNPs-curcumin were synthesized using polyethyleneimine to combine curcumin and UCNPs, based on typical composition of lanthanide nitrates Re(NO)3 (Y:Yb:Er=78%:20%:2%) linked by ethylenediaminetetraacetic acid in sodium fluoride (NaF) matrix, to upconvert NIR to 432 nm light. The product was characterized by size distribution, thermogravimetric analysis, differential scanning calorimetry, and scanning electron microscopy. Growth inhibition of methicillin-resistant Staphylococcus aureus (MRSA) was not only measured in vitro but also investigated on MRSA-induced pneumonia in mice. The results showed that curcumin was covered by UCNPs to form stable nanoparticles whose average size was 179.5 nm and zeta potential was −33.7 mV in normal saline. The UCNPs-curcumin produced singlet oxygen, which reaches a stable level after 30 minutes of irradiation, and took effect on MRSA through bacterial cytoplasm leakage. They alleviated MRSA-induced pneumonia and reduced bacterial counts in lungs with 980 nm irradiation (0.5 W/cm2) on chests of mice. It is confirmed that the UCNPs-curcumin in lungs are activated under NIR irradiation and strengthen their antibacterial effects on MRSA. This research provides a new type of NIR photosensitizer, which plays an important role in phototoxic effects of curcumin in deep tissues under NIR. PMID:25395852

  4. Novel dipeptide nanoparticles for effective curcumin delivery

    PubMed Central

    Alam, Shadab; Panda, Jiban J; Chauhan, Virander S

    2012-01-01

    Background: Curcumin, the principal curcuminoid of the popular Indian spice turmeric, has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin is a major challenge in its development as a useful drug. To enhance the aqueous solubility and bioavailability of curcumin, attempts have been made to encapsulate it in liposomes, polymeric nanoparticles (NPs), lipid-based NPs, biodegradable microspheres, cyclodextrin, and hydrogels. Methods: In this work, we attempted to entrap curcumin in novel self-assembled dipeptide NPs containing a nonprotein amino acid, α, β-dehydrophenylalanine, and investigated the biological activity of dipeptide-curcumin NPs in cancer models both in vitro and in vivo. Results: Of the several dehydrodipeptides tested, methionine-dehydrophenylalanine was the most suitable one for loading and release of curcumin. Loading of curcumin in the dipeptide NPs increased its solubility, improved cellular availability, enhanced its toxicity towards different cancerous cell lines, and enhanced curcumin’s efficacy towards inhibiting tumor growth in Balb/c mice bearing a B6F10 melanoma tumor. Conclusion: These novel, highly biocompatible, and easy to construct dipeptide NPs with a capacity to load and release curcumin in a sustained manner significantly improved curcumin’s cellular uptake without altering its anticancer or other therapeutic properties. Curcumin-dipeptide NPs also showed improved in vitro and in vivo chemotherapeutic efficacy compared to curcumin alone. Such dipeptide-NPs may also improve the delivery of other potent hydrophobic drug molecules that show poor cellular uptake, bioavailability, and efficacy. PMID:22915849

  5. Dissolution enhancement of curcumin via curcumin-prebiotic inulin nanoparticles.

    PubMed

    Fares, Mohammad M; Salem, Mu'taz Sheikh

    2015-01-01

    Dissolution enhancement of curcumin via prebiotic inulin designed to orally deliver poorly water-soluble curcumin at duodenum low acidity (pH 5.5) was investigated. Different prebiotic inulin-curcumin nanoparticles were synthesized in ethanol-water binary system at different pre-adjusted pH values. Characterization via FTIR, XRD and TGA revealed the formation of curcumin-inulin conjugates, whereas surface morphology via SEM and TEM techniques implied the formation of nanoparticle beads and nanoclusters. Prebiotic inulin-curcumin nanoparticles prepared at pH 7.0 demonstrated a maximum curcumin dissolution enhancement of ≈90% with respect to 30% for curcumin alone at pH 5.5. Power law constant values were in accordance with dissolution enhancement investigations. All samples show Fickian diffusion mechanism. XRD investigations confirm that inulin maintain its crystalline structure in curcumin-inulin conjugate structure, which confirms that it can exert successfully its prebiotic role in the gastrointestinal (GI) tract. Therefore, the use of curcumin-inulin nanoparticles can perform dual-mission in the GI tract at the duodenum environment; release of 90% of curcumin followed by prebiotic activity of inulin, which will probably play a significant role in cancer therapeutics for the coming generations. PMID:25632979

  6. Sustained release Curcumin loaded Solid Lipid Nanoparticles

    PubMed Central

    Jourghanian, Parisa; Ghaffari, Solmaz; Ardjmand, Mehdi; Haghighat, Setareh; Mohammadnejad, Mahdieh

    2016-01-01

    Purpose: curcumin is poorly water soluble drug with low bioavailability. Use of lipid systems in lipophilic substances increases solubility and bioavailability of poorly soluble drugs. The aim of this study was to prepare curcumin loaded Solid Lipid Nanoparticles (SLNs) with high loading efficiency, small particle size and prolonged release profile with enhanced antibacterial efficacy. Methods: to synthesize stable SLNs, freeze- Drying was done using mannitol as cryoprotectant. Cholesterol was used as carrier because of good tolerability and biocompatibility. SLNs were prepared using high pressure homogenization method. Results: optimized SLNs had 112 and 163 nm particle size before and after freeze drying, respectively. The prepared SLNs had 71% loading efficiency. 90% of loaded curcumin was released after 48 hours. Morphologic study for formulation was done by taking SEM pictures of curcumin SLNs. Results show the spherical shape of curcumin SLNs. DSC studies were performed to determine prolonged release mechanism. Antimicrobial studies were done to compare the antimicrobial efficacy of curcumin SLNs with free curcumin. DSC studies showed probability of formation of hydrogen bonds between cholesterol and curcumin which resulted in prolonged release of curcumin. Lipid structure of cholesterol could cause enhanced permeability in studied bacteria to increase antibacterial characteristics of curcumin. Conclusion: the designed curcumin SLNs could be candidate for formulation of different dosage forms or cosmeceutical products. PMID:27123413

  7. A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma.

    PubMed

    Hu, Bo; Sun, Ding; Sun, Chao; Sun, Yun-Fan; Sun, Hai-Xiang; Zhu, Qing-Feng; Yang, Xin-Rong; Gao, Ya-Bo; Tang, Wei-Guo; Fan, Jia; Maitra, Anirban; Anders, Robert A; Xu, Yang

    2015-12-25

    Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. PMID:26482853

  8. Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly(butyl cyanoacrylate) nanoparticles.

    PubMed

    Duan, Jinghua; Zhang, Yangde; Han, Shiwei; Chen, Yuxiang; Li, Bo; Liao, Mingmei; Chen, Wei; Deng, Xingming; Zhao, Jinfeng; Huang, Boyun

    2010-11-15

    We have synthesized novel cationic poly(butyl) cyanoacrylate (PBCA) nanoparticles coated with chitosan, formulation of curcumin nanoparticles. The size and zeta potential of prepared curcumin nanoparticles were about 200 nm and +29.11 mV, respectively with 90.04% encapsulation efficiency. The transmission electron microscopy (TEM) study revealed the spherical nature of the prepared nanoparticles along with confirmation of particle size. Curcumin nanoparticles demonstrate comparable in vitro therapeutic efficacy to free curcumin against a panel of human hepatocellular cancer cell lines, as assessed by cell viability (3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide assay [MTT assay]) and proapoptotic effects (annexin V/propidium iodide staining). In vivo, curcumin nanoparticles suppressed hepatocellular carcinoma growth in murine xenograft models and inhibited tumor angiogenesis. The curcumin nanoparticles' mechanism of action on hepatocellular carcinoma cells is a mirror that of free curcumin. PMID:20813175

  9. Curcumin directly inhibits the transport activity of GLUT1.

    PubMed

    Gunnink, Leesha K; Alabi, Ola D; Kuiper, Benjamin D; Gunnink, Stephen M; Schuiteman, Sam J; Strohbehn, Lauren E; Hamilton, Kathryn E; Wrobel, Kathryn E; Louters, Larry L

    2016-06-01

    Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75 μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin's inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75 μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin. PMID:27039889

  10. Preparation of curcumin-loaded poly(ester amine) nanoparticles for the treatment of anti-angiogenesis.

    PubMed

    Ding, Qiuxia; Niu, Ting; Yang, Yi; Guo, Qingfa; Luo, Feng; Qian, Zhiyong

    2014-04-01

    The aim of this study was to prepare curcumin loaded poly(ester amine) nanoparticles and enhance their hydrophilicity and treatment efficacy on anti-angiogenesis zebra fish model. Poly(ester amine) (PEA) copolymer was synthesized in this study. The curcumin-loaded PEA nanoparticles were prepared through double emulsion-solvent evaporation technique. The average particle size of obtained nanoparticles was about 100 nm. The zeta potential of prepared nanoparticles was about 35.8+/-2.4 mV. Transmission electron microscopy demonstrated a narrow size distribution with in vitro release profile demonstrating in vitro slow release of curcumin from the PEA nanoparticles. The in vitro cytotoxicity of the curcumin encapsulated PEA nanoparticles nearly had the same tendency of cytotoxic activity in vitro with free curcumin on tumor cells. In vitro cellular uptake of the curcumin-loaded nanoparticles demonstrated in Hela cells demonstrated that this kind of nanoparticles can be a promising candidate as a drug delivery system to cancer cells. The Cur/PEA nanoparticles more efficiently inhibited angiogenesis (in vivo) in transgenic zebra fish model and Alginate-encapsulated tumor cells than free curcumin. No mortality or significant lesions were observed from histopathological study of the major organs. From our results, we can conclude that the prepared PEA nanoparticles are an efficient curcumin drug delivery system for anti-angiogenesis therapy. PMID:24734515

  11. Curcumin directly inhibits the transport activity of GLUT1

    PubMed Central

    Gunnink, Leesha K.; Alabi, Ola D.; Kuiper, Benjamin D.; Gunnink, Stephen M.; Schuiteman, Sam J.; Strohbehn, Lauren E.; Hamilton, Kathryn E.; Wrobel, Kathryn E.; Louters, Larry L.

    2016-01-01

    Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75 μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin’s inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75 μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin. PMID:27039889

  12. Plasma Proteins Interaction with Curcumin Nanoparticles: Implications in Cancer Therapeutics

    PubMed Central

    Yallapu, Murali M.; Ebeling, Mara C.; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Curcumin, a natural bioactive polyphenol, has been widely investigated as a conventional medicine for centuries. Over the past two decades, major pre-clinical and clinical trials have demonstrated its safe therapeutic profile but clinical translation has been hampered due to rapid degradation, poor water solubility, bioavailability and pharmaco-kinetics. To overcome such translational issues, many laboratories have focused on developing curcumin nanoformulations for cancer therapeutics. In this review, we discuss the evolution of curcumin nanomedicine in cancer therapeutics, the possible interactions between the surface of curcumin nanoparticles and plasma proteins, the role of nanoparticle-protein complex architecture parameters, and the rational design of clinically useful curcumin nanoformulations. Considering all the biologically relevant phenomena, curcumin nanoformulations can be developed as a new neutraceutical or pharmaceutical agent. PMID:23566382

  13. Inhibition of HIV-1 by curcumin A, a novel curcumin analog

    PubMed Central

    Kumari, Namita; Kulkarni, Amol A; Lin, Xionghao; McLean, Charlee; Ammosova, Tatiana; Ivanov, Andrey; Hipolito, Maria; Nekhai, Sergei; Nwulia, Evaristus

    2015-01-01

    Despite the remarkable success of combination antiretroviral therapy at curtailing HIV progression, emergence of drug-resistant viruses, chronic low-grade inflammation, and adverse effects of combination antiretroviral therapy treatments, including metabolic disorders collectively present the impetus for development of newer and safer antiretroviral drugs. Curcumin, a phytochemical compound, was previously reported to have some in vitro anti-HIV and anti-inflammatory activities, but poor bioavailability has limited its clinical utility. To circumvent the bioavailability problem, we derivatized curcumin to sustain retro-aldol decomposition at physiological pH. The lead compound derived, curcumin A, showed increased stability, especially in murine serum where it was stable for up to 25 hours, as compared to curcumin that only had a half-life of 10 hours. Both curcumin and curcumin A showed similar inhibition of one round of HIV-1 infection in cultured lymphoblastoid (also called CEM) T cells (IC50=0.7 μM). But in primary peripheral blood mononuclear cells, curcumin A inhibited HIV-1 more potently (IC50=2 μM) compared to curcumin (IC50=12 μM). Analysis of specific steps of HIV-1 replication showed that curcumin A inhibited HIV-1 reverse transcription, but had no effect on HIV-1 long terminal repeat basal or Tat-induced transcription, or NF-κB-driven transcription at low concentrations that affected reverse transcription. Finally, we showed curcumin A induced expression of HO-1 and decreased cell cycle progression of T cells. Our findings thus indicate that altering the core structure of curcumin could yield more stable compounds with potent antiretroviral and anti-inflammatory activities. PMID:26366056

  14. Inhibition of HIV-1 by curcumin A, a novel curcumin analog.

    PubMed

    Kumari, Namita; Kulkarni, Amol A; Lin, Xionghao; McLean, Charlee; Ammosova, Tatiana; Ivanov, Andrey; Hipolito, Maria; Nekhai, Sergei; Nwulia, Evaristus

    2015-01-01

    Despite the remarkable success of combination antiretroviral therapy at curtailing HIV progression, emergence of drug-resistant viruses, chronic low-grade inflammation, and adverse effects of combination antiretroviral therapy treatments, including metabolic disorders collectively present the impetus for development of newer and safer antiretroviral drugs. Curcumin, a phytochemical compound, was previously reported to have some in vitro anti-HIV and anti-inflammatory activities, but poor bioavailability has limited its clinical utility. To circumvent the bioavailability problem, we derivatized curcumin to sustain retro-aldol decomposition at physiological pH. The lead compound derived, curcumin A, showed increased stability, especially in murine serum where it was stable for up to 25 hours, as compared to curcumin that only had a half-life of 10 hours. Both curcumin and curcumin A showed similar inhibition of one round of HIV-1 infection in cultured lymphoblastoid (also called CEM) T cells (IC50=0.7 μM). But in primary peripheral blood mononuclear cells, curcumin A inhibited HIV-1 more potently (IC50=2 μM) compared to curcumin (IC50=12 μM). Analysis of specific steps of HIV-1 replication showed that curcumin A inhibited HIV-1 reverse transcription, but had no effect on HIV-1 long terminal repeat basal or Tat-induced transcription, or NF-κB-driven transcription at low concentrations that affected reverse transcription. Finally, we showed curcumin A induced expression of HO-1 and decreased cell cycle progression of T cells. Our findings thus indicate that altering the core structure of curcumin could yield more stable compounds with potent antiretroviral and anti-inflammatory activities. PMID:26366056

  15. Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages

    PubMed Central

    Wang, Ji; Kang, Yu-Xia; Pan, Wen; Lei, Wan; Feng, Bin; Wang, Xiao-Juan

    2016-01-01

    Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%–8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions. PMID:27331813

  16. Curcumin inhibits the replication of enterovirus 71 in vitro.

    PubMed

    Qin, Ying; Lin, Lexun; Chen, Yang; Wu, Shuo; Si, Xiaoning; Wu, Heng; Zhai, Xia; Wang, Yan; Tong, Lei; Pan, Bo; Zhong, Xiaoyan; Wang, Tianying; Zhao, Wenran; Zhong, Zhaohua

    2014-08-01

    Human enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD) in children. The epidemic of HFMD has been a public health problem in Asia-Pacific region for decades, and no vaccine and effective antiviral medicine are available. Curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. In this study, we demonstrated that curcumin showed potent antiviral effect again EV71. In Vero cells infected with EV71, the addition of curcumin significantly suppressed the synthesis of viral RNA, the expression of viral protein, and the overall production of viral progeny. Similar with the previous reports, curcumin reduced the production of ROS induced by viral infection. However, the antioxidant property of curcumin did not contribute to its antiviral activity, since N-acetyl-l-cysteine, the potent antioxidant failed to suppress viral replication. This study also showed that extracellular signal-regulated kinase (ERK) was activated by either viral infection or curcumin treatment, but the activated ERK did not interfere with the antiviral effect of curcumin, indicating ERK is not involved in the antiviral mechanism of curcumin. Unlike the previous reports that curcumin inhibited protein degradation through ubiquitin-proteasome system (UPS), we found that curcumin had no impact on UPS in control cells. However, curcumin did reduce the activity of proteasomes which was increased by viral infection. In addition, the accumulation of the short-lived proteins, p53 and p21, was increased by the treatment of curcumin in EV71-infected cells. We further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB, both of which are required for the formation of viral replication complex. We found that curcumin significantly reduced the level of both proteins. Moreover, the decreased expression of either GBF1 or PI4KB by the application of siRNAs was sufficient

  17. Curcumin inhibits the replication of enterovirus 71 in vitro

    PubMed Central

    Qin, Ying; Lin, Lexun; Chen, Yang; Wu, Shuo; Si, Xiaoning; Wu, Heng; Zhai, Xia; Wang, Yan; Tong, Lei; Pan, Bo; Zhong, Xiaoyan; Wang, Tianying; Zhao, Wenran; Zhong, Zhaohua

    2014-01-01

    Human enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD) in children. The epidemic of HFMD has been a public health problem in Asia-Pacific region for decades, and no vaccine and effective antiviral medicine are available. Curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. In this study, we demonstrated that curcumin showed potent antiviral effect again EV71. In Vero cells infected with EV71, the addition of curcumin significantly suppressed the synthesis of viral RNA, the expression of viral protein, and the overall production of viral progeny. Similar with the previous reports, curcumin reduced the production of ROS induced by viral infection. However, the antioxidant property of curcumin did not contribute to its antiviral activity, since N-acetyl-l-cysteine, the potent antioxidant failed to suppress viral replication. This study also showed that extracellular signal-regulated kinase (ERK) was activated by either viral infection or curcumin treatment, but the activated ERK did not interfere with the antiviral effect of curcumin, indicating ERK is not involved in the antiviral mechanism of curcumin. Unlike the previous reports that curcumin inhibited protein degradation through ubiquitin–proteasome system (UPS), we found that curcumin had no impact on UPS in control cells. However, curcumin did reduce the activity of proteasomes which was increased by viral infection. In addition, the accumulation of the short-lived proteins, p53 and p21, was increased by the treatment of curcumin in EV71-infected cells. We further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB, both of which are required for the formation of viral replication complex. We found that curcumin significantly reduced the level of both proteins. Moreover, the decreased expression of either GBF1 or PI4KB by the application of siRNAs was

  18. Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles

    PubMed Central

    Wang, Wenrui; Zhu, Rongrong; Xie, Qian; Li, Ang; Xiao, Yu; Li, Kun; Liu, Hui; Cui, Daxiang; Chen, Yihan; Wang, Shilong

    2012-01-01

    Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of −20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy. PMID:22888226

  19. Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity

    PubMed Central

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena

    2015-01-01

    Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug’s poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1–10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity. PMID:25515789

  20. Curcumin-Loaded PLA Nanoparticles: Formulation and Physical Evaluation.

    PubMed

    Rachmawati, Heni; Yanda, Yulia L; Rahma, Annisa; Mase, Nobuyuki

    2016-01-01

    Curcumin is a polyphenolic compound derived from Curcuma domestica (Zingiberaceae) that possesses diverse pharmacological effects including anti-inflammatory, antioxidant, antimicrobial, and anticarcinogenic activities. Although phase I clinical trials have shown curcumin as a safe drug even at high doses (12 g/day) in humans, poor bioavaibility largely limits its pharmacological activity. Nanoencapsulation in biodegradable polymers is a promising alternative to improve curcumin bioavaibility. In this study, curcumin was encapsulated in biodegradable polymer poly-(lactic acid) (PLA) nanoparticles via the emulsification-solvent evaporation method. Optimization of selected parameters of this method including the type of solvent, surfactant concentration, drug loading, sonication time, and centrifugation speed, were performed to obtain polymeric nano-carriers with optimum characteristics. Dichloromethane was used as the solvent and vitamin E polyethylene glycol succinate (TPGS) was used as the surfactant. Four minutes of sonication time and centrifugation at 10500 rpm were able to produce spherical nanoparticles with average size below 300 nm. The highest encapsulation efficiency was found on PLA nanoparticles containing 5% of curcumin at 89.42 ± 1.04%. The particle size, polydispersity index, zeta potential of 5% curcumin-PLA nanoparticles were 387.50 ± 58.60 nm, 0.289 ± 0.047, and -1.12 mV, respectively. Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies showed partial interaction between the drug and polymer. PMID:27110509

  1. Curcumin-Loaded PLA Nanoparticles: Formulation and Physical Evaluation

    PubMed Central

    Rachmawati, Heni; Yanda, Yulia L.; Rahma, Annisa; Mase, Nobuyuki

    2016-01-01

    Curcumin is a polyphenolic compound derived from Curcuma domestica (Zingiberaceae) that possesses diverse pharmacological effects including anti-inflammatory, antioxidant, antimicrobial, and anticarcinogenic activities. Although phase I clinical trials have shown curcumin as a safe drug even at high doses (12 g/day) in humans, poor bioavaibility largely limits its pharmacological activity. Nanoencapsulation in biodegradable polymers is a promising alternative to improve curcumin bioavaibility. In this study, curcumin was encapsulated in biodegradable polymer poly-(lactic acid) (PLA) nanoparticles via the emulsification-solvent evaporation method. Optimization of selected parameters of this method including the type of solvent, surfactant concentration, drug loading, sonication time, and centrifugation speed, were performed to obtain polymeric nano-carriers with optimum characteristics. Dichloromethane was used as the solvent and vitamin E polyethylene glycol succinate (TPGS) was used as the surfactant. Four minutes of sonication time and centrifugation at 10500 rpm were able to produce spherical nanoparticles with average size below 300 nm. The highest encapsulation efficiency was found on PLA nanoparticles containing 5% of curcumin at 89.42 ± 1.04%. The particle size, polydispersity index, zeta potential of 5% curcumin-PLA nanoparticles were 387.50 ± 58.60 nm, 0.289 ± 0.047, and −1.12 mV, respectively. Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies showed partial interaction between the drug and polymer. PMID:27110509

  2. Curcumin inhibits HIV-1 by promoting Tat protein degradation.

    PubMed

    Ali, Amjad; Banerjea, Akhil C

    2016-01-01

    HIV-1 Tat is an intrinsically unfolded protein playing a pivotal role in viral replication by associating with TAR region of viral LTR. Unfolded proteins are degraded by 20S proteasome in an ubiquitin independent manner. Curcumin is known to activate 20S proteasome and promotes the degradation of intrinsically unfolded p53 tumor suppressor protein. Since HIV-1 Tat protein is largerly unfolded, we hypothesized that Tat may also be targeted through this pathway. Curcumin treated Tat transfected HEK-293T cells showed a dose and time dependent degradation of Tat protein. Contrary to this HIV-1 Gag which is a properly folded protein, remained unaffected with curcumin. Semi-quantitative RT-PCR analysis showed that curcumin treatment did not affect Tat gene transcription. Curcumin increased the rate of Tat protein degradation as shown by cycloheximide (CHX) chase assay. Degradation of the Tat protein is accomplished through proteasomal pathway as proteasomal inhibitor MG132 blocked Tat degradation. Curcumin also decreased Tat mediated LTR promoter transactivation and inhibited virus production from HIV-1 infected cells. Taken together our study reveals a novel observation that curcumin causes potent degradation of Tat which may be one of the major mechanisms behind its anti HIV activity. PMID:27283735

  3. Curcumin inhibits HIV-1 by promoting Tat protein degradation

    PubMed Central

    Ali, Amjad; Banerjea, Akhil C.

    2016-01-01

    HIV-1 Tat is an intrinsically unfolded protein playing a pivotal role in viral replication by associating with TAR region of viral LTR. Unfolded proteins are degraded by 20S proteasome in an ubiquitin independent manner. Curcumin is known to activate 20S proteasome and promotes the degradation of intrinsically unfolded p53 tumor suppressor protein. Since HIV-1 Tat protein is largerly unfolded, we hypothesized that Tat may also be targeted through this pathway. Curcumin treated Tat transfected HEK-293T cells showed a dose and time dependent degradation of Tat protein. Contrary to this HIV-1 Gag which is a properly folded protein, remained unaffected with curcumin. Semi-quantitative RT-PCR analysis showed that curcumin treatment did not affect Tat gene transcription. Curcumin increased the rate of Tat protein degradation as shown by cycloheximide (CHX) chase assay. Degradation of the Tat protein is accomplished through proteasomal pathway as proteasomal inhibitor MG132 blocked Tat degradation. Curcumin also decreased Tat mediated LTR promoter transactivation and inhibited virus production from HIV-1 infected cells. Taken together our study reveals a novel observation that curcumin causes potent degradation of Tat which may be one of the major mechanisms behind its anti HIV activity. PMID:27283735

  4. Polymeric Curcumin Nanoparticle Pharmacokinetics and Metabolism in Bile Duct Cannulated Rats

    PubMed Central

    Zou, Peng; Helson, Lawrence; Maitra, Anirban; Stern, Stephan T.; McNeil, Scott E.

    2013-01-01

    The objective of this study was to compare the pharmacokinetics and metabolism of polymeric nanoparticle encapsulated (nanocurcumin), and solvent solubilized curcumin formulations in Sprague Dawley (SD) rats. Nanocurcumin is currently under development for cancer therapy. Since free, unencapsulated curcumin is rapidly metabolized and excreted in rats, upon i.v. administration of nanocurcumin only nanoparticle encapsulated curcumin can be detected in plasma samples. Hence, the second objective of this study was to utilize the metabolic instability of curcumin to assess in vivo drug release from nanocurcumin. Nanocurcumin and solvent solubilized curcumin were administered at 10 mg curcumin/kg by jugular vein to bile duct-cannulated male SD rats (n = 5). Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the solvent solubilized curcumin. Nanocurcumin also increased the relative abundance of curcumin and glucuronides in bile, but did not dramatically alter urine and tissue metabolite profiles. The observed increase in biliary and urinary excretion of both curcumin and metabolites for the nanocurcumin formulation suggested rapid, “burst” release of curcumin. Although the burst release observed in this study is a limitation for targeted tumor delivery, nanocurcumin still exhibits major advantages over solvent solubilized curcumin, as the nanoformulation does not result in the lung accumulation observed for the solvent solubilized curcumin and increases overall systemic curcumin exposure. Additionally, the remaining encapsulated curcumin fraction following burst release is available for tumor delivery via the enhanced permeation and retention effect commonly observed for nanoparticle formulations. PMID:23534919

  5. Active curcumin nanoparticles formed from a volatile microemulsion template.

    PubMed

    Margulis, K; Srinivasan, S; Ware, M J; Summers, H D; Godin, B; Magdassi, S

    2014-01-01

    We report on biological performance of organic nanoparticles formed by a simple method based on rapid solvent removal from a volatile microemulsion. The particular focus of the study was on testing the suitability of the method for substances soluble in partially water-miscible organic solvents as well as on evaluating the therapeutic activity of the resultant nanoparticles. Curcumin was employed as a model for hydrophobic drug, and, as it is soluble in water-miscible organic solvents, it was successfully incorporated into a new cyclopentanone-water microemulsion system. During rapid solvent removal by spray-drying, the nanometric droplets of the microemulsion were converted into nanoparticles containing amorphous curcumin with the average size of 20.2±3.4 nm, having ζ potential of -36.2 ±1.8 mV. These nanoparticles were dispersible in water and retained the high loading of the active substance. The therapeutic activity of the resulting nanoparticles was demonstrated in a pancreatic cancer cell line Panc-1. The effective concentration for reducing the metabolic activity was found to be 11.5 μM for nanoparticles compared with 19.5 μM for free curcumin. PMID:25485110

  6. A unique mechanism of curcumin inhibition on F1 ATPase.

    PubMed

    Sekiya, Mizuki; Hisasaka, Ryosuke; Iwamoto-Kihara, Atsuko; Futai, Masamitsu; Nakanishi-Matsui, Mayumi

    2014-10-01

    ATP synthase (F-ATPase) function depends upon catalytic and rotation cycles of the F1 sector. Previously, we found that F1 ATPase activity is inhibited by the dietary polyphenols, curcumin, quercetin, and piceatannol, but that the inhibitory kinetics of curcumin differs from that of the other two polyphenols (Sekiya et al., 2012, 2014). In the present study, we analyzed Escherichia coli F1 ATPase rotational catalysis to identify differences in the inhibitory mechanism of curcumin versus quercetin and piceatannol. These compounds did not affect the 120° rotation step for ATP binding and ADP release, though they significantly increased the catalytic dwell duration for ATP hydrolysis. Analysis of wild-type F1 and a mutant lacking part of the piceatannol binding site (γΔ277-286) indicates that curcumin binds to F1 differently from piceatannol and quercetin. The unique inhibitory mechanism of curcumin is also suggested from its effect on F1 mutants with defective β-γ subunit interactions (γMet23 to Lys) or β conformational changes (βSer174 to Phe). These results confirm that smooth interaction between each β subunit and entire γ subunit in F1 is pertinent for rotational catalysis. PMID:25230139

  7. Curcumin loaded pH-sensitive nanoparticles for the treatment of colon cancer.

    PubMed

    Prajakta, Dandekar; Ratnesh, Jain; Chandan, Kumar; Suresh, Subramanian; Grace, Samuel; Meera, Venkatesh; Vandana, Patravale

    2009-10-01

    The investigation was aimed at designing pH-sensitive, polymeric nanoparticles of curcumin, a natural anti-cancer agent, for the treatment of colon cancer. The objective was to enhance the bioavailability of curcumin, simultaneously reducing the required dose through selective targeting to colon. Eudragit S100 was chosen to aid targeting since the polymer dissolves at colonic pH to result in selective colonic release of the entrapped drug. Solvent emulsion-evaporation technique was employed to formulate the nanoparticles. Various process parameters were optimized and the optimized formulation was evaluated for particle size distribution and encapsulation efficiency before subjecting to freeze-drying. The freeze dried product was characterized for particle size, drug content, DSC studies, particle morphology. Anti-cancer potential of the formulation was demonstrated by MTT assay in HT-29 cell line. Nanometric, homogeneous, spherical particles were obtained with encapsulation efficiency of 72%. Freeze-dried nanoparticles exhibited a negative surface charge, drug content of > 99% and presence of drug in amorphous form which may result in possible enhanced absorption. MTT assay demonstrated almost double inhibition of the cancerous cells by nanoparticles, as compared to curcumin alone, at the concentrations tested. Enhanced action may be attributed to size influenced improved cellular uptake, and may result in reduction of overall dose requirement. Results indicate the potential for in vivo studies to establish the clinical application of the formulation. PMID:20201417

  8. Inhibition of curcumin on myeloid-derived suppressor cells is requisite for controlling lung cancer.

    PubMed

    Liu, Dan; You, Ming; Xu, Yujun; Li, Fanlin; Zhang, Dongya; Li, Xiujun; Hou, Yayi

    2016-10-01

    Lung cancer remains the leading cause of cancer mortality. Myeloid-derived suppressor cells (MDSCs) are potent immune-suppressive cells and present in most cancer patients. Recently, several studies have shown that curcumin inhibits the expansion of MDSCs in some cancers. However, it is not clear how curcumin modulates the suppressive function of MDSCs, and whether curcumin achieves anti-tumor effects via regulating the expansion of MDSCs in lung cancer. Here, our results showed that curcumin significantly inhibited tumor growth in a Lewis lung carcinoma (LLC) isogenic tumor model. Curcumin reduced the accumulation of MDSCs in spleen and tumor tissue in LLC isogenic model. And curcumin promoted the maturation and differentiation of MDSCs in tumor tissue. Notably, curcumin inhibited the expression level of immune suppressive factors of MDSCs, arginase-1 (Arg-1) and ROS, in purified MDSCs from tumor tissue in vivo. Expectedly, curcumin also inhibited the immunosuppressive function of isolated MDSCs from tumor tissue and spleen of tumor bearing mice in vitro. Moreover, curcumin decreased the level of IL-6 in the tumor tissue and serum from LLC-bearing mice. Taken together, curcumin indeed possesses anti-cancer effect and inhibits the accumulation and function of MDSCs. And curcumin reduces the level of IL-6 in tumor-bearing mice to impair the expansion and function of MDSCs. These results suggest that inhibition of MDSCs in tumor is requisite for controlling lung cancer. PMID:27497194

  9. Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

    NASA Astrophysics Data System (ADS)

    Banerjee, Subhamoy; Sahoo, Amaresh Kumar; Chattopadhyay, Arun; Sankar Ghosh, Siddhartha

    2014-08-01

    The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

  10. Curcumin inhibits activation of TRPM2 channels in rat hepatocytes

    PubMed Central

    Kheradpezhouh, E.; Barritt, G.J.; Rychkov, G.Y.

    2015-01-01

    Oxidative stress is a hallmark of many liver diseases including viral and drug-induced hepatitis, ischemia-reperfusion injury, and non-alcoholic steatohepatitis. One of the consequences of oxidative stress in the liver is deregulation of Ca2+ homeostasis, resulting in a sustained elevation of the free cytosolic Ca2+ concentration ([Ca2+]c) in hepatocytes, which leads to irreversible cellular damage. Recently it has been shown that liver damage induced by paracetamol and subsequent oxidative stress is, in large part, mediated by Ca2+ entry through Transient Receptor Potential Melastatin 2 (TRPM2) channels. Involvement of TRPM2 channels in hepatocellular damage induced by oxidative stress makes TRPM2 a potential therapeutic target for treatment of a range of oxidative stress-related liver diseases. We report here the identification of curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a natural plant-derived polyphenol in turmeric spice, as a novel inhibitor of TRPM2 channel. Presence of 5 µM curcumin in the incubation medium prevented the H2O2- and paracetamol-induced [Ca2+]c rise in rat hepatocytes. Furthermore, in patch clamping experiments incubation of hepatocytes with curcumin inhibited activation of TRPM2 current by intracellular ADPR with IC50 of approximately 50 nM. These findings enhance understanding of the actions of curcumin and suggest that the known hepatoprotective properties of curcumin are, at least in part, mediated through inhibition of TRPM2 channels. PMID:26609559

  11. Curcumin inhibits activation of TRPM2 channels in rat hepatocytes.

    PubMed

    Kheradpezhouh, E; Barritt, G J; Rychkov, G Y

    2016-04-01

    Oxidative stress is a hallmark of many liver diseases including viral and drug-induced hepatitis, ischemia-reperfusion injury, and non-alcoholic steatohepatitis. One of the consequences of oxidative stress in the liver is deregulation of Ca(2+) homeostasis, resulting in a sustained elevation of the free cytosolic Ca(2+) concentration ([Ca(2+)]c) in hepatocytes, which leads to irreversible cellular damage. Recently it has been shown that liver damage induced by paracetamol and subsequent oxidative stress is, in large part, mediated by Ca(2+) entry through Transient Receptor Potential Melastatin 2 (TRPM2) channels. Involvement of TRPM2 channels in hepatocellular damage induced by oxidative stress makes TRPM2 a potential therapeutic target for treatment of a range of oxidative stress-related liver diseases. We report here the identification of curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a natural plant-derived polyphenol in turmeric spice, as a novel inhibitor of TRPM2 channel. Presence of 5µM curcumin in the incubation medium prevented the H2O2- and paracetamol-induced [Ca(2+)]c rise in rat hepatocytes. Furthermore, in patch clamping experiments incubation of hepatocytes with curcumin inhibited activation of TRPM2 current by intracellular ADPR with IC50 of approximately 50nM. These findings enhance understanding of the actions of curcumin and suggest that the known hepatoprotective properties of curcumin are, at least in part, mediated through inhibition of TRPM2 channels. PMID:26609559

  12. Curcumin Inhibits Rift Valley Fever Virus Replication in Human Cells*

    PubMed Central

    Narayanan, Aarthi; Kehn-Hall, Kylene; Senina, Svetlana; Lundberg, Lindsay; Van Duyne, Rachel; Guendel, Irene; Das, Ravi; Baer, Alan; Bethel, Laura; Turell, Michael; Hartman, Amy Lynn; Das, Bhaskar; Bailey, Charles; Kashanchi, Fatah

    2012-01-01

    Rift Valley fever virus (RVFV) is an arbovirus that is classified as a select agent, an emerging infectious virus, and an agricultural pathogen. Understanding RVFV-host interactions is imperative to the design of novel therapeutics. Here, we report that an infection by the MP-12 strain of RVFV induces phosphorylation of the p65 component of the NFκB cascade. We demonstrate that phosphorylation of p65 (serine 536) involves phosphorylation of IκBα and occurs through the classical NFκB cascade. A unique, low molecular weight complex of the IKK-β subunit can be observed in MP-12-infected cells, which we have labeled IKK-β2. The IKK-β2 complex retains kinase activity and phosphorylates an IκBα substrate. Inhibition of the IKK complex using inhibitors impairs viral replication, thus alluding to the requirement of an active IKK complex to the viral life cycle. Curcumin strongly down-regulates levels of extracellular infectious virus. Our data demonstrated that curcumin binds to and inhibits kinase activity of the IKK-β2 complex in infected cells. Curcumin partially exerts its inhibitory influence on RVFV replication by interfering with IKK-β2-mediated phosphorylation of the viral protein NSs and by altering the cell cycle of treated cells. Curcumin also demonstrated efficacy against ZH501, the fully virulent version of RVFV. Curcumin treatment down-regulated viral replication in the liver of infected animals. Our data point to the possibility that RVFV infection may result in the generation of novel versions of host components (such as IKK-β2) that, by virtue of altered protein interaction and function, qualify as unique therapeutic targets. PMID:22847000

  13. Actin-curcumin interaction: insights into the mechanism of actin polymerization inhibition.

    PubMed

    Dhar, Gopa; Chakravarty, Devlina; Hazra, Joyita; Dhar, Jesmita; Poddar, Asim; Pal, Mahadeb; Chakrabarti, Pinak; Surolia, Avadhesha; Bhattacharyya, Bhabatarak

    2015-02-01

    Curcumin, derived from rhizomes of the Curcuma longa plant, is known to possess a wide range of medicinal properties. We have examined the interaction of curcumin with actin and determined their binding and thermodynamic parameters using isothermal titration calorimetry. Curcumin is weakly fluorescent in aqueous solution, and binding to actin enhances fluorescence several fold with a large blue shift in the emission maximum. Curcumin inhibits microfilament formation, which is similar to its role in inhibiting microtubule formation. We synthesized a series of stable curcumin analogues to examine their affinity for actin and their ability to inhibit actin self-assembly. Results show that curcumin is a ligand with two symmetrical halves, each of which possesses no activity individually. Oxazole, pyrazole, and acetyl derivatives are less effective than curcumin at inhibiting actin self-assembly, whereas a benzylidiene derivative is more effective. Cell biology studies suggest that disorganization of the actin network leads to destabilization of filaments in the presence of curcumin. Molecular docking reveals that curcumin binds close to the cytochalasin binding site of actin. Further molecular dynamics studies reveal a possible allosteric effect in which curcumin binding at the "barbed end" of actin is transmitted to the "pointed end", where conformational changes disrupt interactions with the adjacent actin monomer to interrupt filament formation. Finally, the recognition and binding of actin by curcumin is yet another example of its unique ability to target multiple receptors. PMID:25564154

  14. PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.

    PubMed

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena; Tian, Xuebi; Liu, Ying; Wang, Zaijie Jim

    2016-01-01

    Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin's mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling. PMID:26744842

  15. Curcumin-incorporated albumin nanoparticles and its tumor image

    NASA Astrophysics Data System (ADS)

    Gong, Guangming; Pan, Qinqin; Wang, Kaikai; Wu, Rongchun; Sun, Yong; Lu, Ying

    2015-01-01

    Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

  16. Preparation and Characterization of PEG-albumin-curcumin Nanoparticles Intended to Treat Breast Cancer

    PubMed Central

    Thadakapally, R.; Aafreen, Arshiya; Aukunuru, J.; Habibuddin, M.; Jogala, S.

    2016-01-01

    The aim of present research was to prepare novel serum stable long circulating polymeric nanoparticles for curcumin with a modification to the well known and novel nanoparticle albumin bound technology. polyethylene glycol-albumin-curcumin nanoparticles were prepared using serum albumin and poly ethylene glycol using desolvation technique. Nanoparticles were characterized for encapsulation efficiency, particle size and surface morphology. Drug excipient compatibility was determined using fourier transform infrared spectroscopy. Physical state of the drug in the formulations was known by differential scanning colorimetry. In vitro release and solubility of the drug from nanoparticles were determined. In vivo Drug release, tissue uptake and kupffer cell uptake was determined with optimized nanoformulation in rats after intravenous administration. Cell viability assay was determined using breast cancer cell line MD-MB-231. Entrapment efficiency for prepared nanoparticle was above 95%. The polyethylene glycol-albumin-curcumin nanoparticles exhibited an interesting release profile with small initial burst followed by slower and controlled release. Solubility of the drug from the formulation was increased. A sustained release of drug from nanoparticles was observed for 35 days in both in vitro and in vivo studies with the optimized formulation. Polyethylene glycol-albumin-curcumin nanoparticles showed lesser liver and kupffer cell uptake as compared to that of curcumin-albumin nanoparticles suggesting the bestowment of stealthness to nanoparticles with pegylation. Also, the antiproliferative activity of polyethylene glycol-albumin-curcumin nanoparticle formulation was more as compared to native curcumin. Polyethylene glycol-albumin-curcumin nanoparticles thus developed can be conveniently used in breast cancer with improved efficacy compared to conventional therapies and as an alternate to nanoparticle albumin bound technology which is used in producing Abraxane, albumin

  17. c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles.

    PubMed

    Paunovic, Verica; Ristic, Biljana; Markovic, Zoran; Todorovic-Markovic, Biljana; Kosic, Milica; Prekodravac, Jovana; Kravic-Stevovic, Tamara; Martinovic, Tamara; Micusik, Matej; Spitalsky, Zdeno; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2016-04-01

    Indian spice curcumin is known for its anticancer properties, but the anticancer mechanisms of nanoparticulate curcumin have not been completely elucidated. We here investigated the in vitro anticancer effect of blue light (470 nm, 1 W)-irradiated curcumin nanoparticles prepared by tetrahydrofuran/water solvent exchange, using U251 glioma, B16 melanoma, and H460 lung cancer cells as targets. The size of curcumin nanocrystals was approximately 250 nm, while photoexcitation induced their oxidation and partial agglomeration. Although cell membrane in the absence of light was almost impermeable to curcumin nanoparticles, photoexcitation stimulated their internalization. While irradiation with blue light (1-8 min) or nanocurcumin (1.25-10 μg/ml) alone was only marginally toxic to tumor cells, photoexcited nanocurcumin displayed a significant cytotoxicity depending both on the irradiation time and nanocurcumin concentration. Photoexcited nanocurcumin induced phosphorylation of c-Jun N-terminal kinase (JNK), mitochondrial depolarization, caspase-3 activation, and cleavage of poly (ADP-ribose) polymerase, indicating apoptotic cell death. Accordingly, pharmacologial inhibition of JNK and caspase activity rescued cancer cells from photoexcited nanocurcumin. On the other hand, antioxidant treatment did not reduce photocytotoxicity of nanocurcumin, arguing against the involvement of oxidative stress. By demonstrating the ability of photoexcited nanocurcumin to induce oxidative-stress independent, JNK- and caspase-dependent apoptosis, our results support its further investigation in cancer therapy. PMID:27106025

  18. Cathepsin L knockdown enhances curcumin-mediated inhibition of growth, migration, and invasion of glioma cells.

    PubMed

    Fei, Yao; Xiong, Yajie; Zhao, Yifan; Wang, Wenjuan; Han, Meilin; Wang, Long; Tan, Caihong; Liang, Zhongqin

    2016-09-01

    Curcumin can be used to prevent and treat cancer. However, its exact underlying molecular mechanisms remain poorly understood. Cathepsin L, a lysosomal cysteine protease, is overexpressed in several cancer types. This study aimed to determine the role of cathepsin L in curcumin-mediated inhibition of growth, migration, and invasion of glioma cells. Results revealed that the activity of cathepsin L was enhanced in curcumin-treated glioma cells. Cathepsin L knockdown induced by RNA interference significantly promoted curcumin-induced cytotoxicity, apoptosis, and cell cycle arrest. The knockdown also inhibited the migration and invasion of glioma cells. Our results suggested that the inhibition of cathepsin L can enhance the sensitivity of glioma cells to curcumin. Therefore, cathepsin L may be a new target to enhance the efficacy of curcumin against cancers. PMID:27373979

  19. PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα

    PubMed Central

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena; Tian, Xuebi; Liu, Ying; Wang, Zaijie Jim

    2016-01-01

    Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin’s mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling. PMID:26744842

  20. Polyelectrolyte complex nanoparticles from cationised gelatin and sodium alginate for curcumin delivery.

    PubMed

    Sarika, P R; James, Nirmala Rachel

    2016-09-01

    Self assembled hybrid polyelectrolyte complex (PEC) nanoparticles are prepared from cationically modified gelatin and sodium alginate (Alg) by electrostatic complexation between the polymers. Cationised gelatin (CG) is prepared by the reaction of gelatin with ethylenediamine. Structural changes in gelatin, after modification with ethylenediamine are investigated by XRD and (1)H NMR spectroscopy. Hybrid polyelectrolyte nanoparticles, labeled CG/Alg, are prepared by simple mixing of CG and Alg. CG/Alg complex shows spherical morphology as confirmed by scanning electron microscopy. These polyelectrolyte complex nanoparticles can be used for the encapsulation and delivery of natural antioxidant curcumin to carcinoma cells. CG/Alg nanoparticles show curcumin encapsulation efficiency of 69% and exhibit sustained release of curcumin in vitro. Anticancer activity of curcumin loaded CG/Alg nanoparticles towards MCF-7 cells is disclosed by MTT assay. Intracellular uptake of the drug encapsulated nanoparticles is confirmed by fluorescent imaging. PMID:27185149

  1. Core-shell biopolymer nanoparticle delivery systems: synthesis and characterization of curcumin fortified zein-pectin nanoparticles.

    PubMed

    Hu, Kun; Huang, Xiaoxia; Gao, Yongqing; Huang, Xulin; Xiao, Hang; McClements, David Julian

    2015-09-01

    Biopolymer core-shell nanoparticles were fabricated using a hydrophobic protein (zein) as the core and a hydrophilic polysaccharide (pectin) as the shell. Particles were prepared by coating cationic zein nanoparticles with anionic pectin molecules using electrostatic deposition (pH 4). The core-shell nanoparticles were fortified with curcumin (a hydrophobic bioactive molecule) at a high loading efficiency (>86%). The resulting nanoparticles were spherical, relatively small (diameter ≈ 250 nm), and had a narrow size distribution (polydispersity index ≈ 0.24). The encapsulated curcumin was in an amorphous (rather than crystalline form) as detected by differential scanning calorimetry (DSC). Fourier transform infrared (FTIR) and Raman spectra indicated that the encapsulated curcumin interacted with zein mainly through hydrophobic interactions. The nanoparticles were converted into a powdered form that had good water-dispersibility. These core-shell biopolymer nanoparticles could be useful for incorporating curcumin into functional foods and beverages, as well as dietary supplements and pharmaceutical products. PMID:25842338

  2. Curcumin inhibition of angiogenesis and adipogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The growth of new blood vessels or angiogenesis is necessary for the growth of adipose tissue. Adipokines produced by fat cells stimulate this process. Some dietary polyphenols with antiangiogenic activity may suppress adipose tissue growth not only by inhibiting angiogenesis, but also by interferin...

  3. Curcumin inhibits bTREK-1 K+ channels and stimulates cortisol secretion from adrenocortical cells

    PubMed Central

    Enyeart, Judith A.; Liu, Haiyan; Enyeart, John J.

    2008-01-01

    Bovine adrenal zona fasciculata (AZF) cells express bTREK-1 K+ channels that set the resting membrane potential. Inhibition of these channels by adrenocorticotropic hormone (ACTH) is coupled to membrane depolarization and cortisol secretion. Curcumin, a phytochemical with medicinal properties extracted from the spice turmeric, was found to modulate both bTREK-1 K+ currents and cortisol secretion from AZF cells. In whole-cell patch clamp experiments, curcumin inhibited bTREK-1 with an IC50 of 0.93μM by a mechanism that was voltage-independent. bTREK-1 inhibition by curcumin occurred through interaction with an external binding site and was independent of ATP hydrolysis. Curcumin produced a concentration-dependent increase in cortisol secretion that persisted for up to 24 h. At a maximally effective concentration of 50 μM, curcumin increased secretion as much as10-fold. These results demonstrate that curcumin potently inhibits bTREK-1 K+ channels and stimulates cortisol secretion from bovine AZF cells. The inhibition of bTREK-1 by curcumin may be linked to cortisol secretion through membrane depolarization. Since TREK-1 is widely expressed in a variety of cells, it is likely that some of the biological actions of curcumin, including its therapeutic effects, may be mediated through inhibition of these K+ channels. PMID:18406348

  4. Drastic nickel ion removal from aqueous solution by curcumin-capped Ag nanoparticles

    NASA Astrophysics Data System (ADS)

    Bettini, S.; Pagano, R.; Valli, L.; Giancane, G.

    2014-08-01

    A completely green synthesis protocol has been adopted to obtain silver nanoaggregates capped by the natural compound (1E, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-diene), also known as curcumin. The synthesis has been monitored by infrared, Raman, visible and fluorescence spectroscopies. Characterization confirms that curcumin reduces and caps the nanoparticles, and such a procedure allows its solubility in water and drastically increases curcumin stability. Silver nanoparticles (AgNPs)/curcumin complex has been dispersed in a water solution containing a known nickel ion concentration. After three days, a grey precipitate is observed and nickel concentration in the solution is reduced by about 70%.A completely green synthesis protocol has been adopted to obtain silver nanoaggregates capped by the natural compound (1E, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-diene), also known as curcumin. The synthesis has been monitored by infrared, Raman, visible and fluorescence spectroscopies. Characterization confirms that curcumin reduces and caps the nanoparticles, and such a procedure allows its solubility in water and drastically increases curcumin stability. Silver nanoparticles (AgNPs)/curcumin complex has been dispersed in a water solution containing a known nickel ion concentration. After three days, a grey precipitate is observed and nickel concentration in the solution is reduced by about 70%. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02583k

  5. Development and performance evaluation of novel nanoparticles of a grafted copolymer loaded with curcumin.

    PubMed

    Mutalik, Srinivas; Suthar, Neelam A; Managuli, Renuka S; Shetty, Pallavi K; Avadhani, Kiran; Kalthur, Guruprasad; Kulkarni, Raghavendra V; Thomas, Ranjeny

    2016-05-01

    Inflammatory bowel disease (IBD) is an inflammatory condition with mucosal ulceration, edema and hemorrhage of gastrointestinal tract. Curcumin has been shown to mitigate colitis in animal models. However, its usefulness is reduced due to poor pharmacokinetic behavior and low oral bioavailability. To address this, novel pH-sensitive hydrolyzed polyacrylamide-grafted-xanthan gum (PAAm-g-XG) nanoparticles (NPs) loaded with curcumin were prepared for colonic delivery. Optimized nanoparticles (CN20) were spherical, with an average size of 425 nm. A negligible amount of curcumin (≈8%) was released from CN20 NPs in pH 1.2 and 4.5 solutions. When the pH was increased to 7.2, curcumin release was comparatively faster than that observed with pH 1.2 and 4.5 collectively. In pH 6.8 solution, excellent release of curcumin was observed. Highest curcumin release was observed when rat caecal contents were incorporated in pH 6.8 solution, indicating microflora-dependent drug release property of NPs. In acetic acid-induced IBD in rats, curcumin NPs reduced myeloperoxidase and nitrite levels, prevented weight loss and attenuated colonic inflammation. Curcumin was better absorbed systemically in nanoparticulate form with increased Cmax (∼3 fold) and AUC (∼2.5 fold) than when delivered as free curcumin. We demonstrate successful development of grafted co-polymeric NPs containing drug suitable for colon targeting. PMID:26851203

  6. Curcumin-loaded N,O-carboxymethyl chitosan nanoparticles for cancer drug delivery.

    PubMed

    Anitha, A; Maya, S; Deepa, N; Chennazhi, K P; Nair, S V; Jayakumar, R

    2012-01-01

    Chitosan (CS) and its carboxymethyl derivatives are smart biopolymers that are non-toxic, biocompatible and biodegradable, and, hence, suitable for various biomedical applications, such as drug delivery, gene therapy and tissue engineering. Curcumin is a major chemotherapeutic agent with antioxidant, anti-inflammatory, anti-proliferative, anticancer and antimicrobial effects. However, the potential of curcumin as a chemotherapeutic agent is limited by its hydrophobicity and poor bioavailability. In this work, we developed a nanoformulation of curcumin in a carboxymethyl chitosan (CMC) derivative, N,O-carboxymethyl chitosan (N,O-CMC). The curcumin-loaded N,O-CMC (curcumin-N,O-CMC) nanoparticles were characterized using DLS, AFM, SEM, FT-IR and XRD. DLS studies revealed nanoparticles with a mean diameter of 150 ± 30 nm. AFM and SEM confirmed that the particles have a spherical morphology within the size range of 150 ± 30 nm. Curcumin was entrapped with in N,O-CMC nanopartcles with an efficiency of 80%. The in vitro drug-release profile was studied at different pH (7.4 and 4.5) at 37°C for different incubation periods with and without lysozyme. Cytotoxicity studies using MTT assay indicated that curcumin-N,O-CMC nanoparticles showed specific toxicity towards cancer cells and non-toxicity to normal cells. Cellular uptake of curcumin-N,O-CMC nanoparticles was analyzed by fluorescence microscopy and was reconfirmed by flow cytometry. Overall, these results indicate that like previously reported curcumin loaded O-CMC nanoparticles, N,O-CMC will also be an efficient nanocarrier for delivering curcumin to cancer cells. PMID:21722423

  7. Curcumin inhibits HCV replication by induction of heme oxygenase-1 and suppression of AKT

    PubMed Central

    CHEN, MING-HO; LEE, MING-YANG; CHUANG, JING-JING; LI, YI-ZHEN; NING, SIN-TZU; CHEN, JUNG-CHOU; LIU, YI-WEN

    2012-01-01

    Although hepatitis C virus (HCV) affects approximately 130–170 million people worldwide, no vaccines are available. HCV is an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, leading to the need for liver transplantation. In this study, curcumin, a constituent used in traditional Chinese medicine, has been evaluated for its anti-HCV activity and mechanism, using a human hepatoma cell line containing the HCV genotype 1b subgenomic replicon. Below the concentration of 20% cytotoxicity, curcumin dose-dependently inhibited HCV replication by luciferase reporter gene assay, HCV RNA detection and HCV protein analysis. Under the same conditions, curcumin also dose-dependently induced heme oxygenase-1 with the highest induction at 24 h. Hemin, a heme oxygenase-1 inducer, also inhibited HCV protein expression in a dose-dependent manner. The knockdown of heme oxygenase-1 partially reversed the curcumin-inhibited HCV protein expression. In addition to the heme oxygenase-1 induction, signaling molecule activities of AKT, extracellular signal-regulated kinases (ERK) and nuclear factor-κB (NF-κB) were inhibited by curcumin. Using specific inhibitors of PI3K-AKT, MEK-ERK and NF-κB, the results suggested that only PI3K-AKT inhibition is positively involved in curcumin-inhibited HCV replication. Inhibition of ERK and NF-κB was likely to promote HCV protein expression. In summary, curcumin inhibited HCV replication by heme oxygenase-1 induction and AKT pathway inhibition. Although curcumin also inhibits ERK and NF-κB activities, it slightly increased the HCV protein expression. This result may provide information when curcumin is used as an adjuvant in anti-HCV therapy. PMID:22922731

  8. Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer

    PubMed Central

    Chen, Chun-Chieh; Sureshbabul, Munisamy; Chen, Huei-Wen; Lin, Yu-Shuang; Lee, Jen-Yi; Hong, Qi-Sheng; Yang, Ya-Chien

    2013-01-01

    Colorectal cancer (CRC) is a serious public health problem that results due to changes of diet and various environmental stress factors in the world. Curcumin is a traditional medicine used for treatment of a wide variety of tumors. However, antimetastasis mechanism of curcumin on CRC has not yet been completely investigated. Here, we explored the underlying molecular mechanisms of curcumin on metastasis of CRC cells in vitro and in vivo. Curcumin significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo. We found that curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells. Curcumin inhibits focal adhesion kinase (FAK) phosphorylation and enhances the expressions of several extracellular matrix components which play a critical role in invasion and metastasis. Curcumin reduces CD24 expression in a dose-dependent manner in CRC cells. Moreover, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT. These results suggest that curcumin executes its antimetastasis function through downregulation of Sp-1, FAK, and CD24 and by promoting E-cadherin expression in CRC cells. PMID:23970932

  9. Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer.

    PubMed

    Chen, Chun-Chieh; Sureshbabul, Munisamy; Chen, Huei-Wen; Lin, Yu-Shuang; Lee, Jen-Yi; Hong, Qi-Sheng; Yang, Ya-Chien; Yu, Sung-Liang

    2013-01-01

    Colorectal cancer (CRC) is a serious public health problem that results due to changes of diet and various environmental stress factors in the world. Curcumin is a traditional medicine used for treatment of a wide variety of tumors. However, antimetastasis mechanism of curcumin on CRC has not yet been completely investigated. Here, we explored the underlying molecular mechanisms of curcumin on metastasis of CRC cells in vitro and in vivo. Curcumin significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo. We found that curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells. Curcumin inhibits focal adhesion kinase (FAK) phosphorylation and enhances the expressions of several extracellular matrix components which play a critical role in invasion and metastasis. Curcumin reduces CD24 expression in a dose-dependent manner in CRC cells. Moreover, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT. These results suggest that curcumin executes its antimetastasis function through downregulation of Sp-1, FAK, and CD24 and by promoting E-cadherin expression in CRC cells. PMID:23970932

  10. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer's disease model via canonical Wnt/β-catenin pathway.

    PubMed

    Tiwari, Shashi Kant; Agarwal, Swati; Seth, Brashket; Yadav, Anuradha; Nair, Saumya; Bhatnagar, Priyanka; Karmakar, Madhumita; Kumari, Manisha; Chauhan, Lalit Kumar Singh; Patel, Devendra Kumar; Srivastava, Vikas; Singh, Dhirendra; Gupta, Shailendra Kumar; Tripathi, Anurag; Chaturvedi, Rajnish Kumar; Gupta, Kailash Chand

    2014-01-28

    Neurogenesis, a process of generation of new neurons, is reported to be reduced in several neurodegenerative disorders including Alzheimer's disease (AD). Induction of neurogenesis by targeting endogenous neural stem cells (NSC) could be a promising therapeutic approach to such diseases by influencing the brain self-regenerative capacity. Curcumin, a neuroprotective agent, has poor brain bioavailability. Herein, we report that curcumin-encapsulated PLGA nanoparticles (Cur-PLGA-NPs) potently induce NSC proliferation and neuronal differentiation in vitro and in the hippocampus and subventricular zone of adult rats, as compared to uncoated bulk curcumin. Cur-PLGA-NPs induce neurogenesis by internalization into the hippocampal NSC. Cur-PLGA-NPs significantly increase expression of genes involved in cell proliferation (reelin, nestin, and Pax6) and neuronal differentiation (neurogenin, neuroD1, neuregulin, neuroligin, and Stat3). Curcumin nanoparticles increase neuronal differentiation by activating the Wnt/β-catenin pathway, involved in regulation of neurogenesis. These nanoparticles caused enhanced nuclear translocation of β-catenin, decreased GSK-3β levels, and increased promoter activity of the TCF/LEF and cyclin-D1. Pharmacological and siRNA-mediated genetic inhibition of the Wnt pathway blocked neurogenesis-stimulating effects of curcumin. These nanoparticles reverse learning and memory impairments in an amyloid beta induced rat model of AD-like phenotypes, by inducing neurogenesis. In silico molecular docking studies suggest that curcumin interacts with Wif-1, Dkk, and GSK-3β. These results suggest that curcumin nanoparticles induce adult neurogenesis through activation of the canonical Wnt/β-catenin pathway and may offer a therapeutic approach to treating neurodegenerative diseases such as AD, by enhancing a brain self-repair mechanism. PMID:24467380

  11. Microfluidic fabrication of cationic curcumin nanoparticles as an anti-cancer agent

    NASA Astrophysics Data System (ADS)

    Dev, Selvi; Prabhakaran, Praseetha; Filgueira, Luis; Iyer, K. Swaminathan; Raston, Colin L.

    2012-03-01

    Curcumin nanoparticles of less than 50 nm in diameter are accessible using a continuous flow microfluidic rotating tube processor (RTP) under scalable conditions, at room temperature. A mixture of DDAB and Pluronic F127 renders higher stability of the curcumin nanoparticles in physiological pH 7.4 for up to eight hours. The nanoparticles have enhanced cytotoxicity in estrogens receptor negative and positive breast cancer cell lines compared with free curcumin.Curcumin nanoparticles of less than 50 nm in diameter are accessible using a continuous flow microfluidic rotating tube processor (RTP) under scalable conditions, at room temperature. A mixture of DDAB and Pluronic F127 renders higher stability of the curcumin nanoparticles in physiological pH 7.4 for up to eight hours. The nanoparticles have enhanced cytotoxicity in estrogens receptor negative and positive breast cancer cell lines compared with free curcumin. Electronic supplementary information (ESI) available: Materials and methods, DLS, DSC, Fluorescence, UV. See DOI: 10.1039/c2nr11502f

  12. Curcumin

    PubMed Central

    Chaudhari, Soham P.; Tam, Alison Y.; Barr, Jason A.

    2015-01-01

    Background: Herbal medicines are used by thousands of patients all over the world. However, they can often cause adverse effects. Turmeric, made from the root of Curcuma, longa, is a yellow spice used throughout South Asia for its flavor as well as for its medicinal properties. Curcumin is the main ingredient in turmeric. It is known for downregulating the expression of various proinflammatory cytokines and has been studied for its antiinflammatory mechanism. However, it has also been reported to cause contact dermatitis. Kumkum, a turmeric-based powder applied by Hindu women on their foreheads, has also been found as an allergen. Objective: The authors have reviewed the anti-inflammatory properties of curcumin and reports of contact dermatitis to understand the possible harmful effects of this commonly used spice, while also examining its beneficial role in dermatologic conditions. They aim to increase awareness regarding this common herb and its prevalent use not only in South Asia, but also in North America. Methods: A thorough literature search of the PubMed database was conducted to identify studies that examined the antiinflammatory role of curcumin and its role in contact dermatitis. Results: Eleven studies demonstrate that although curcumin does have antiinflammatory properties, it is an allergen. Conclusion: Curcumin has many valuable properties that can be exploited to treat dermatologic conditions. However, patients and dermatologists must be keen of possible allergic reactions. Further studies are needed to completely understand this widely used herb and its efficacy in dermatology. PMID:26705440

  13. Preparation and anti-cancer activity of polymer-encapsulated curcumin nanoparticles

    NASA Astrophysics Data System (ADS)

    Thu Ha, Phuong; Huong Le, Mai; Nhung Hoang, Thi My; Thu Huong Le, Thi; Quang Duong, Tuan; Tran, Thi Hong Ha; Tran, Dai Lam; Phuc Nguyen, Xuan

    2012-09-01

    Curcumin (Cur) is a yellow compound isolated from rhizome of the herb curcuma longa. Curcumin possesses antioxidant, anti-inflammatory, anti-carcinogenic and antimicrobial properties, and suppresses proliferation of many tumor cells. However, the clinical application of curcumin in cancer treatment is considerably limited due to its serious poor delivery characteristics. In order to increase the hydrophilicity and drug delivery capability, we encapsulated curcumin into copolymer PLA-TPGS, 1,3-beta-glucan (Glu), O-carboxymethyl chitosan (OCMCs) and folate-conjugated OCMCs (OCMCs-Fol). These polymer-encapsulated curcumin nanoparticles (Cur-PLA-TPGS, Cur-Glu, Cur-OCMCs and Cur-OCMCs-Fol) were characterized by infrared (IR), fluorescence (FL), photoluminescence (PL) spectra, field emission scanning electron microscopy (FE-SEM), and found to be spherical particles with an average size of 50–100 nm, being suitable for drug delivery applications. They were much more soluble in water than not only free curcumin but also other biodegradable polymer-encapsulated curcumin nanoparticles. The anti-tumor promoting assay was carried out, showing the positive effects of Cur-Glu and Cur-PLA-TPGS on tumor promotion of Hep-G2 cell line in vitro. Confocal microscopy revealed that the nano-sized curcumin encapsulated by polymers OCMCs and OCMCs-Fol significantly enhanced the cellular uptake (cancer cell HT29 and HeLa).

  14. Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice.

    PubMed

    Amano, Chie; Minematsu, Hideki; Fujita, Kazuyo; Iwashita, Shinki; Adachi, Masaki; Igarashi, Koichi; Hinuma, Shuji

    2015-01-01

    To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticles, the liposomes containing curcumin, ranged from 60 to 100 nm. Flow cytometric analyses revealed that after intraperitoneal administration of the liposomes containing curcumin into mice, these were incorporated mainly by macrophages positive for F4/80, CD36, and CD11b antigens. Peritoneal cells prepared from mice injected in vivo with the liposomes containing curcumin apparently decreased interleukin-6-producing activities. Major changes in body weight and survival rates in the mice were not observed after administrating the liposomes containing curcumin. These results indicate that the liposomes containing curcumin are safe and useful for the selective suppression of macrophages in vivo in mice. PMID:26361331

  15. Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice

    PubMed Central

    Amano, Chie; Minematsu, Hideki; Fujita, Kazuyo; Iwashita, Shinki; Adachi, Masaki; Igarashi, Koichi; Hinuma, Shuji

    2015-01-01

    To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticles, the liposomes containing curcumin, ranged from 60 to 100 nm. Flow cytometric analyses revealed that after intraperitoneal administration of the liposomes containing curcumin into mice, these were incorporated mainly by macrophages positive for F4/80, CD36, and CD11b antigens. Peritoneal cells prepared from mice injected in vivo with the liposomes containing curcumin apparently decreased interleukin-6-producing activities. Major changes in body weight and survival rates in the mice were not observed after administrating the liposomes containing curcumin. These results indicate that the liposomes containing curcumin are safe and useful for the selective suppression of macrophages in vivo in mice. PMID:26361331

  16. Curcumin Implants, not Curcumin Diet Inhibits Estrogen-Induced Mammary Carcinogenesis in ACI Rats

    PubMed Central

    Bansal, Shyam S.; kausar, Hina; Vadhanam, Manicka V.; Ravoori, Srivani; Pan, Jianmin; Rai, Shesh N.; Gupta, Ramesh C.

    2014-01-01

    Curcumin is widely known for its anti-oxidant, anti-inflammatory and anti-proliferative activities in cell culture studies. However, poor oral bioavailability limited its efficacy in animal and clinical studies. Recently, we developed polymeric curcumin implants that circumvents oral bioavailability issues, and tested their potential against 17β-estradiol (E2)-mediated mammary tumorigenesis. Female ACI rats were administered curcumin either via diet (1,000 ppm) or via polymeric curcumin implants (two 2-cm; 200 mg each; 20% drug load) 4 days prior to grafting a subcutaneous E2 silastic implant (1.2 cm, 9 mg E2). Implants were changed after 4½ months to provide higher curcumin dose at the appearance of palpable tumors. The animals were euthanized after 3 weeks, 3 months and after the tumor incidence reached >80% (~6 months) in control animals. The curcumin administered via implants resulted in significant reduction in both the tumor multiplicity (2±1 vs 5±3; p=0.001) and tumor volume (184±198 mm3 vs 280±141 mm3; p=0.0283); the dietary curcumin, however, was ineffective. Dietary curcumin increased hepatic CYP1A and CYP1B1 activities without any effect on CYP3A4 activity whereas curcumin implants increased both CYP1A and CYP3A4 activities but decreased CYP1B1 activity in presence of E2. Since CYP1A and 3A4 metabolize most of the E2 to its non-carcinogenic 2-OH metabolite and CYP1B1 produces potentially carcinogenic 4-OH metabolite, favorable modulation of these CYPs via systemically delivered curcumin could be one of the potential mechanisms. The analysis of plasma and liver by HPLC showed substantially higher curcumin levels via implants versus the dietary route despite substantially higher dose administered. PMID:24501322

  17. Curcumin inhibits cellular condensation and alters microfilament organization during chondrogenic differentiation of limb bud mesenchymal cells.

    PubMed

    Kim, Dong Kyun; Kim, Song Ja; Kang, Shin Sung; Jin, Eun Jung

    2009-09-30

    Curcumin is a well known natural polyphenol product isolated from the rhizome of the plant Curcuma longa, anti-inflammatory agent for arthritis by inhibiting synthesis of inflammatory prostaglandins. However, the mechanisms by which curcumin regulates the functions of chondroprogenitor, such as proliferation, precartilage condensation, cytoskeletal organization or overall chondrogenic behavior, are largely unknown. In the present report, we investigated the effects and signaling mechanism of curcumin on the regulation of chondrogenesis. Treating chick limb bud mesenchymal cells with curcumin suppressed chondrogenesis by stimulating apoptotic cell death. It also inhibited reorganization of the actin cytoskeleton into a cortical pattern concomitant with rounding of chondrogenic competent cells and down-regulation of integrin beta1 and focal adhesion kinase (FAK) phosphorylation. Curcumin suppressed the phosphorylation of Akt leading to Akt inactivation. Activation of Akt by introducing a myristoylated, constitutively active form of Akt reversed the inhibitory actions of curcumin during chondrogenesis. In summary, for the first time, we describe biological properties of curcumin during chondrogenic differentiation of chick limb bud mesenchymal cells. Curcumin suppressed chondrogenesis by stimulating apoptotic cell death and down-regulating integrin-mediated reorganization of actin cytoskeleton via modulation of Akt signaling. PMID:19478554

  18. Curcumin inhibits lipolysis via suppression of ER stress in adipose tissue and prevents hepatic insulin resistance.

    PubMed

    Wang, Lulu; Zhang, Bangling; Huang, Fang; Liu, Baolin; Xie, Yuan

    2016-07-01

    Curcumin is natural polyphenol with beneficial effects on lipid and glucose metabolism and this study aimed to investigate the effects of curcumin on lipolysis and hepatic insulin resistance. Endoplasmic reticulum (ER) stress and lipolysis signaling in adipose and FFA influx, lipid deposits, and glucose production in liver were examined. Palmitate challenge and high-fat diet feeding evoked ER stress-associated lipolysis with cAMP accumulation in adipose tissue. Curcumin treatment inhibited adipose tissue ER stress by dephosphorylation of inositol-requiring enzyme 1α and eukaryotic initiation factor 2α and reduced cAMP accumulation by preserving phosphodiesterase 3B induction. Knockdown of mitogen-activated protein kinase α1/2α with siRNAs diminished such effects of curcumin. As a result from downregulation of cAMP, curcumin blocked protein kinase (PK)A/hormone-sensitive lipase lipolysis signaling, and thereby reduced glycerol and FFA release from adipose tissue. Curcumin reduced FFA influx into the liver by blocking FFA trafficking, and then prevented diacylglycerol deposits and PKCε translocation in the liver, resultantly improving insulin action in the suppression of hepatic gluconeogenesis. Curcumin decreased adipose lipolysis by attenuating ER stress through the cAMP/PKA pathway, reduced FFA influx into the liver by blocking FFA trafficking, and thereby improved insulin sensitivity to inhibit hepatic glucose production. These findings suggested a novel pathway of curcumin to prevent lipid deposits and insulin resistance in liver by beneficial regulation of adipose function. PMID:27220352

  19. Preparation of curcumin-loaded pluronic F127/chitosan nanoparticles for cancer therapy

    NASA Astrophysics Data System (ADS)

    Phuc Le, Thi Minh; Phuc Pham, Van; Lua Dang, Thi Minh; Huyen La, Thi; Hanh Le, Thi; Huan Le, Quang

    2013-06-01

    Nanoparticles (NPs) have been proven to be an effective delivery system with few side effects for anticancer drugs. In this study, curcumin-loaded NPs have been prepared by an ionic gelation method using chitosan (Chi) and pluronic®F-127 (PF) as carriers to deliver curcumin to the target cancer cells. Prepared NPs were characterized using Zetasizer, fluorescence microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Our results showed that the encapsulation efficiency of curcumin was approximately 50%. The average size of curcumin-loaded PF/Chi NPs was 150.9 nm, while the zeta potential was 5.09 mV. Cellular uptake of curcumin-loaded NPs into HEK293 cells was confirmed by fluorescence microscopy.

  20. Tumour growth inhibition and anti-angiogenic effects using curcumin correspond to combined PDE2 and PDE4 inhibition.

    PubMed

    Abusnina, Abdurazzag; Keravis, Thérèse; Zhou, Qingwei; Justiniano, Hélène; Lobstein, Annelise; Lugnier, Claire

    2015-02-01

    Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis by stimulating endothelial cells. Increase in cyclic AMP (cAMP) level inhibits VEGF-induced endothelial cell proliferation and migration. Cyclic nucleotide phosphodiesterases (PDEs), which specifically hydrolyse cyclic nucleotides, are critical in the regulation of this signal transduction. We have previously reported that PDE2 and PDE4 up-regulations in human umbilical vein endothelial cells (HUVECs) are implicated in VEGF-induced angiogenesis and that inhibition of PDE2 and PDE4 activities prevents the development of the in vitro angiogenesis by increasing cAMP level, as well as the in vivo chicken embryo angiogenesis. We have also shown that polyphenols are able to inhibit PDEs. The curcumin having anti-cancer properties, the present study investigated whether PDE2 and PDE4 inhibitors and curcumin could have similar in vivo anti-tumour properties and whether the anti-angiogenic effects of curcumin are mediated by PDEs. Both PDE2/PDE4 inhibitor association and curcumin significantly inhibited in vivo tumour growth in C57BL/6N mice. In vitro, curcumin inhibited basal and VEGF-stimulated HUVEC proliferation and migration and delayed cell cycle progression at G0/G1, similarly to the combination of selective PDE2 and PDE4 inhibitors. cAMP levels in HUVECs were significantly increased by curcumin, similarly to rolipram (PDE4 inhibitor) and BAY-60-550 (PDE2 inhibitor) association, indicating cAMP-PDE inhibitions. Moreover, curcumin was able to inhibit VEGF-induced cAMP-PDE activity without acting on cGMP-PDE activity and to modulate PDE2 and PDE4 expressions in HUVECs. The present results suggest that curcumin exerts its in vitro anti-angiogenic and in vivo anti-tumour properties through combined PDE2 and PDE4 inhibition. PMID:25230992

  1. Formation of curcumin nanoparticles via solution-enhanced dispersion by supercritical CO2.

    PubMed

    Zhao, Zheng; Xie, Maobin; Li, Yi; Chen, Aizheng; Li, Gang; Zhang, Jing; Hu, Huawen; Wang, Xinyu; Li, Shipu

    2015-01-01

    In order to enhance the bioavailability of poorly water-soluble curcumin, solution-enhanced dispersion by supercritical carbon dioxide (CO2) (SEDS) was employed to prepare curcumin nanoparticles for the first time. A 2(4) full factorial experiment was designed to determine optimal processing parameters and their influence on the size of the curcumin nanoparticles. Particle size was demonstrated to increase with increased temperature or flow rate of the solution, or with decreased precipitation pressure, under processing conditions with different parameters considered. The single effect of the concentration of the solution on particle size was not significant. Curcumin nanoparticles with a spherical shape and the smallest mean particle size of 325 nm were obtained when the following optimal processing conditions were adopted: P = 20 MPa, T = 35°C, flow rate of solution = 0.5 mL·min(-1), concentration of solution = 0.5%. Fourier transform infrared (FTIR) spectroscopy measurement revealed that the chemical composition of curcumin basically remained unchanged. Nevertheless, X-ray powder diffraction (XRPD) and thermal analysis indicated that the crystalline state of the original curcumin decreased after the SEDS process. The solubility and dissolution rate of the curcumin nanoparticles were found to be higher than that of the original curcumin powder (approximately 1.4 μg/mL vs 0.2 μg/mL in 180 minutes). This study revealed that supercritical CO2 technologies had a great potential in fabricating nanoparticles and improving the bioavailability of poorly water-soluble drugs. PMID:25995627

  2. Formation of curcumin nanoparticles via solution-enhanced dispersion by supercritical CO2

    PubMed Central

    Zhao, Zheng; Xie, Maobin; Li, Yi; Chen, Aizheng; Li, Gang; Zhang, Jing; Hu, Huawen; Wang, Xinyu; Li, Shipu

    2015-01-01

    In order to enhance the bioavailability of poorly water-soluble curcumin, solution-enhanced dispersion by supercritical carbon dioxide (CO2) (SEDS) was employed to prepare curcumin nanoparticles for the first time. A 24 full factorial experiment was designed to determine optimal processing parameters and their influence on the size of the curcumin nanoparticles. Particle size was demonstrated to increase with increased temperature or flow rate of the solution, or with decreased precipitation pressure, under processing conditions with different parameters considered. The single effect of the concentration of the solution on particle size was not significant. Curcumin nanoparticles with a spherical shape and the smallest mean particle size of 325 nm were obtained when the following optimal processing conditions were adopted: P =20 MPa, T =35°C, flow rate of solution =0.5 mL·min−1, concentration of solution =0.5%. Fourier transform infrared (FTIR) spectroscopy measurement revealed that the chemical composition of curcumin basically remained unchanged. Nevertheless, X-ray powder diffraction (XRPD) and thermal analysis indicated that the crystalline state of the original curcumin decreased after the SEDS process. The solubility and dissolution rate of the curcumin nanoparticles were found to be higher than that of the original curcumin powder (approximately 1.4 μg/mL vs 0.2 μg/mL in 180 minutes). This study revealed that supercritical CO2 technologies had a great potential in fabricating nanoparticles and improving the bioavailability of poorly water-soluble drugs. PMID:25995627

  3. TPGS-Stabilized Curcumin Nanoparticles Exhibit Superior Effect on Carrageenan-Induced Inflammation in Wistar Rat.

    PubMed

    Rachmawati, Heni; Safitri, Dewi; Pradana, Aditya Trias; Adnyana, I Ketut

    2016-01-01

    Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract. PMID:27537907

  4. Liposome-Encapsulated Curcumin Suppresses Neuroblastoma Growth Through Nuclear Factor-κB Inhibition

    PubMed Central

    Orr, W. Shannon; Denbo, Jason W.; Saab, Karim R.; Myers, Adrianne L.; Ng, Catherine Y.; Zhou, Junfang; Morton, Christopher L.; Pfeffer, Lawrence M.; Davidoff, Andrew M.

    2012-01-01

    Background Nuclear factor-κB (NF-κB) has been implicated in tumor cell proliferation and survival, and tumor angiogenesis. We sought to evaluate the effects of curcumin, an inhibitor of NF-κB, on a xenograft model on disseminated neuroblastoma. Methods For in vitro studies, neuroblastoma cell lines, NB1691, CHLA-20, and SK-N-AS, were treated with varying doses of liposomal curcumin. Disseminated neuroblastoma was established in vivo by tail vein injection of NB1691-luc cells into SCID mice which were then treated with 50mg/kg/day of liposomal curcumin 5 days/week intraperitoneal. Results Curcumin suppressed NF-κB activation and proliferation of all neuroblastoma cell lines in vitro. In vivo, curcumin treatment resulted in a significant decrease in disseminated tumor burden. Curcumin treated tumors had decreased NF-κB activity and an associated significant decrease in tumor cell proliferation and an increase in tumor cell apoptosis, as well as a decrease in tumor VEGF levels and microvessel density. Conclusions Liposomal curcumin suppressed neuroblastoma growth, with treated tumors showing a decrease in NF-kB activity. Our results suggest that liposomal curcumin maybe a viable option for the treatment of neuroblastoma that works via inhibiting the NF-κB pathway. PMID:22284765

  5. Increase of a group of PTC(+) transcripts by curcumin through inhibition of the NMD pathway.

    PubMed

    Feng, Dairong; Su, Ruey-Chyi; Zou, Liping; Triggs-Raine, Barbara; Huang, Shangzhi; Xie, Jiuyong

    2015-08-01

    Nonsense-mediated mRNA decay (NMD), an mRNA surveillance mechanism, eliminates premature termination codon-containing (PTC⁺) transcripts. For instance, it maintains the homeostasis of splicing factors and degrades aberrant transcripts of human genetic disease genes. Here we examine the inhibitory effect on the NMD pathway and consequent increase of PTC+ transcripts by the dietary compound curcumin. We have found that several PTC⁺ transcripts including that of serine/arginine-rich splicing factor 1 (SRSF1) were specifically increased in cells by curcumin. We also observed a similar curcumin effect on the PTC⁺ mutant transcript from a Tay-Sachs-causing HEXA allele or from a beta-globin reporter gene. The curcumin effect was accompanied by significantly reduced expression of the NMD factors UPF1, 2, 3A and 3B. Consistently, in chromatin immunoprecipitation assays, curcumin specifically reduced the occupancy of acetyl-histone H3 and RNA polymerase II at the promoter region (-376 to -247nt) of human UPF1, in a time- and dosage-dependent way. Importantly, knocking down UPF1 abolished or substantially reduced the difference of PTC(+) transcript levels between control and curcumin-treated cells. The disrupted curcumin effect was efficiently rescued by expression of exogenous Myc-UPF1 in the knockdown cells. Together, our data demonstrate that a group of PTC⁺ transcripts are stabilized by a dietary compound curcumin through the inhibition of UPF factor expression and the NMD pathway. PMID:25934542

  6. Evolution of availability of curcumin inside poly-lactic-co-glycolic acid nanoparticles: impact on antioxidant and antinitrosant properties

    PubMed Central

    Betbeder, Didier; Lipka, Emmanuelle; Howsam, Mike; Carpentier, Rodolphe

    2015-01-01

    Purpose Curcumin exhibits antioxidant properties potentially beneficial for human health; however, its use in clinical applications is limited by its poor solubility and relative instability. Nanoparticles exhibit interesting features for the efficient distribution and delivery of curcumin into cells, and could also increase curcumin stability in biological systems. There is a paucity of information regarding the evolution of the antioxidant properties of nanoparticle-encapsulated curcumin. Method We described a simple method of curcumin encapsulation in poly-lactic-co-glycolic acid (PLGA) nanoparticles without the use of detergent. We assessed, in epithelial cells and in an acellular model, the evolution of direct antioxidant and antinitrosant properties of free versus PLGA-encapsulated curcumin after storage under different conditions (light vs darkness, 4°C vs 25°C vs 37°C). Results In epithelial cells, endocytosis and efflux pump inhibitors showed that the increased antioxidant activity of PLGA-encapsulated curcumin relied on bypassing the efflux pump system. Acellular assays showed that the antioxidant effect of curcumin was greater when loaded in PLGA nanoparticles. Furthermore, we observed that light decreased, though heat restored, antioxidant activity of PLGA-encapsulated curcumin, probably by modulating the accessibility of curcumin to reactive oxygen species, an observation supported by results from quenching experiments. Moreover, we demonstrated a direct antinitrosant activity of curcumin, enhanced by PLGA encapsulation, which was increased by light exposure. Conclusion These results suggest that the antioxidant and antinitrosant activities of encapsulated curcumin are light sensitive and that nanoparticle modifications over time and with temperature may facilitate curcumin contact with reactive oxygen species. These results highlight the importance of understanding effects of nanoparticle maturation on an encapsulated drug’s activity. PMID

  7. Curcumin-loaded γ-cyclodextrin liposomal nanoparticles as delivery vehicles for osteosarcoma

    PubMed Central

    Dhule, Santosh S.; Penfornis, Patrice; Frazier, Trivia; Walker, Ryan; Feldman, Joshua; Tan, Grace; He, Jibao; Alb, Alina; John, Vijay; Pochampally, Radhika

    2016-01-01

    The delivery of curcumin, a broad-spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma (OS). Curcumin is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumin’s potential was evaluated against cancer models of mesenchymal (OS) and epithelial origin (breast cancer). The resulting 2-Hydroxypropyl-γ-cyclodextrin/curcumin - liposome complex shows promising anticancer potential both in vitro and in vivo against KHOS OS cell line and MCF-7 breast cancer cell line. An interesting aspect is that liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro in comparison with DMSO-curcumin induced autophagic cell death. In addition, the efficiency of the liposomal curcumin formulation was confirmed in vivo using a xenograft OS model. Curcumin-loaded γ-cyclodextrin liposomes indicate significant potential as delivery vehicles for the treatment of cancers of different tissue origin. From the Clinical Editor Curcumin-loaded γ-cyclodextrin liposomes were demonstrated in vitro to have significant potential as delivery vehicles for the treatment of cancers of mesenchymal and epithelial origin. Differences between mechanisms of cell death were also evaluated. PMID:21839055

  8. Magnetic purification of curcumin from Curcuma longa rhizome by novel naked maghemite nanoparticles.

    PubMed

    Magro, Massimiliano; Campos, Rene; Baratella, Davide; Ferreira, Maria Izabela; Bonaiuto, Emanuela; Corraducci, Vittorino; Uliana, Maíra Rodrigues; Lima, Giuseppina Pace Pereira; Santagata, Silvia; Sambo, Paolo; Vianello, Fabio

    2015-01-28

    Naked maghemite nanoparticles, namely, surface active maghemite nanoparticles (SAMNs), characterized by a diameter of about 10 nm, possessing peculiar colloidal stability, surface chemistry, and superparamagnetism, present fundamental requisites for the development of effective magnetic purification processes for biomolecules in complex matrices. Polyphenolic molecules presenting functionalities with different proclivities toward iron chelation were studied as probes for testing SAMN suitability for magnetic purification. Thus, the binding efficiency and reversibility on SAMNs of phenolic compounds of interest in the pharmaceutical and food industries, namely, catechin, tyrosine, hydroxytyrosine, ferulic acid, coumaric acid, rosmarinic acid, naringenin, curcumin, and cyanidin-3-glucoside, were evaluated. Curcumin emerged as an elective compound, suitable for magnetic purification by SAMNs from complex matrices. A combination of curcumin, demethoxycurcumin, and bis-demethoxycurcumin was recovered by a single magnetic purification step from extracts of Curcuma longa rhizomes, with a purity >98% and a purification yield of 45%, curcumin being >80% of the total purified curcuminoids. PMID:25584520

  9. Curcumin as fluorescent probe for directly monitoring in vitro uptake of curcumin combined paclitaxel loaded PLA-TPGS nanoparticles

    NASA Astrophysics Data System (ADS)

    Nguyen, Hoai Nam; Thu Ha, Phuong; Sao Nguyen, Anh; Nguyen, Dac Tu; Doan Do, Hai; Nguyen Thi, Quy; Nhung Hoang Thi, My

    2016-06-01

    Theranostics, which is the combination of both therapeutic and diagnostic capacities in one dose, is a promising tool for both clinical application and research. Although there are many chromophores available for optical imaging, their applications are limited due to the photobleaching property or intrinsic toxicity. Curcumin, a natural compound extracted from the rhizome of curcuma longa, is well known thanks to its bio-pharmaceutical activities and strong fluorescence as biocompatible probe for bio-imaging. In this study, we aimed to fabricate a system with dual functions: diagnostic and therapeutic, based on poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) micelles co-loaded curcumin (Cur) and paclitaxel (PTX). Two kinds of curcumin nanoparticle (NP) were fabricated and characterized by Fourier transform infrared spectroscopy, field emission scanning electron microscopy and dynamic light scattering methods. The cellular uptake and fluorescent activities of curcumin in these systems were also tested by bioassay studies, and were compared with paclitaxe-oregon. The results showed that (Cur + PTX)-PLA-TPGS NPs is a potential system for cancer theranostics.

  10. Accelerated Recovery of Endothelium Function after Stent Implantation with the Use of a Novel Systemic Nanoparticle Curcumin

    PubMed Central

    Lu, Qi; Ye, Fang; Yang, Xiangjun; Gu, Qingqing; Wang, Peng; Zhu, Jianhua; Shen, Li; Gong, Feirong

    2015-01-01

    Curcumin was reported to exhibit a wide range of pharmacological effects including antioxidant, anti-inflammatory, and antiproliferative activities and significantly prevent smooth muscle cells migration. In the present study, a novel kind of curcumin loaded nanoparticles (Cur-NP) has been prepared and characterized with the aim of inhibiting inflammation formation and accelerating the healing process of the stented arteries. Cur-NP was administrated intravenously after stent implantation twice a week and detailed tissue responses were evaluated. The results demonstrated that intravenous administration of Cur-NP after stent implantation accelerated endothelial cells restoration and endothelium function recovery and may potentially be an effective therapeutic alternative to reduce adverse events for currently available drug eluting stents. PMID:26167481

  11. Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres

    PubMed Central

    Chang, Run; Sun, Linlin; Webster, Thomas J

    2015-01-01

    Osteosarcoma is the most frequent primary malignant form of bone cancer, comprising 30% of all bone cancer cases. The objective of this in vitro study was to develop a treatment against osteosarcoma with higher selectivity toward osteosarcoma cells and lower cytotoxicity toward normal healthy osteoblast cells. Curcumin (or diferuloylmethane) has been found to have antioxidant and anticancer effects by multiple cellular pathways. However, it has lower water solubility and a higher degradation rate in alkaline conditions. In this study, the amphiphilic peptide C18GR7RGDS was used as a curcumin carrier in aqueous solution. This peptide contains a hydrophobic aliphatic tail group leading to their self-assembly by hydrophobic interactions, as well as a hydrophilic head group composed of an arginine-rich and an arginine-glycine-aspartic acid structure. Through characterization by transmission electron microscopy, self-assembled structures of spherical amphiphilic nanoparticles (APNPs) with diameters of 10–20 nm in water and phosphate-buffered saline were observed, but this structure dissociated when the pH value was reduced to 4. Using a method of codissolution with acetic acid and dialysis tubing, the solubility of curcumin was enhanced and a homogeneous solution was formed in the presence of APNPs. Successful encapsulation of curcumin in APNPs was then confirmed by Fourier transform infrared and X-ray diffraction analyses. The cytotoxicity and cellular uptake of the APNP/curcumin complexes on both osteosarcoma and normal osteoblast cell lines were also evaluated by methyl-thiazolyl-tetrazolium assays and confocal fluorescence microscopy. The results showed that the curcumin-loaded APNPs had significant selective cytotoxicity against MG-63 osteosarcoma cells when compared with normal osteoblasts. We have demonstrated for the first time that APNPs can encapsulate hydrophobic curcumin in their hydrophobic cores, and curcumin-loaded APNPs could be an innovative treatment

  12. Towards scale-up and regulatory shelf-stability testing of curcumin encapsulated polyester nanoparticles.

    PubMed

    Grama, Charitra N; Venkatpurwar, Vinod P; Lamprou, Dimitrios A; Ravi Kumar, M N V

    2013-06-01

    This study reports scale-up and shelf-stability of curcumin encapsulated poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles. The curcumin encapsulated PLGA nanoparticles were prepared by emulsification solvent evaporation/diffusion, and large quantities were made by varying the homogenisation time (5, 15 and 30 min). The particle size decreased as the homogenisation duration increased from 5 to 30 min, and the particles were spherical as confirmed by atomic force microscopy. For the large-scale preparations, the mean particles size was found to be 288.7 ± 3.4 (polydispersity index 0.15 ± 0.01) with curcumin entrapment 52.5 ± 4.3 %, which were comparable to the lab-scale preparations. The curcumin encapsulated nanoparticles were freeze-dried using sucrose (5 %, w/v) as a cryoprotectant. The freeze-dried nanoparticles were subjected to 6-month stability study as per the International Conference on Harmonisation guideline at room temperature and refrigerated storage conditions. Intermediate sampling was done (monthly), and the nanoparticles were thoroughly characterised for particle size, entrapment efficiency, surface morphology and crystallinity, which were compared to fresh preparations. The curcumin encapsulated PLGA nanoparticles were found to be stable at refrigerated as well as room temperature storage test conditions indicated by their particle characteristics. X-ray diffraction results confirm amorphous nature of curcumin on nano-encapsulation that stays intact after freeze drying and 6-month stability testing. Together these data offer possibility of producing large quantities of polymer nanoparticles that are suitable for room as well as refrigerated storage conditions opening up possibilities to conduct repeated dosings in a chronic setting or regulatory toxicology studies of such nanomedicines. PMID:25788136

  13. Curcumin Triggers DNA Damage and Inhibits Expression of DNA Repair Proteins in Human Lung Cancer Cells.

    PubMed

    Ting, Chien-Yi; Wang, Hsin-Ell; Yu, Chien-Chih; Liu, Hsin-Chung; Liu, Yu-Chang; Chiang, I-Tsang

    2015-07-01

    The study goal was to evaluate the effects of curcumin on DNA damage and expression of DNA-repair proteins in human lung cancer. Thus, NCI-H460 cells were used to study the effects of curcumin on DNA damage and repair in vitro. We investigated curcumin induces DNA damage by comet the assay and 4',6-diamidino-2-phenylindole (DAPI) staining. The DNA damage/repair-related protein levels were examined and monitored by western blotting and confocal microscopy. Curcumin significantly increased the length of comet tails and DNA condensation in NCI-H460 cells. Curcumin reduced expression of DNA-repair proteins such as 14-3-3 protein sigma (14-3-3σ), O6-methylguanine-DNA methyltransferase (MGMT), breast cancer susceptibility gene 1 (BRCA1), and mediator of DNA damage checkpoint 1 (MDC1). Curcumin also increased phosphorylation of p53 and Histone H2A.X (S140) in the nuclei of NCI-H460 cells. Taken together, our findings indicated that curcumin triggered DNA damage and inhibited expression of DNA-repair-associated proteins in NCI-H460 cells. PMID:26124332

  14. Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid

    PubMed Central

    Khatri, Dharmendra Kumar; Juvekar, Archana Ramesh

    2016-01-01

    Background: Curcumin and ellagic are the natural polyphenols having a wide range of pharmacological actions. They have been reported to have their use in various neurological disorders. Objective: This study was aimed to evaluate the effect of curcumin and ellagic acid on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters which are pivotal for neuronal development and function. Materials and Methods: The in vitro effects of these selected polyphenols on MAO activities in mitochondria isolated from rat brains were examined. Brain mitochondria were assayed for MAO type-B (MAO-B) using benzylamine as substrates. Rat brain mitochondrial MAO preparation was used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver–Burk plot. Results: MAO activity was inhibited by curcumin and ellagic acid; however, higher half maximal inhibitory concentrations of curcumin (500.46 nM) and ellagic acid (412.24 nM) were required compared to the known MAO-B inhibitor selegiline. It is observed that the curcumin and ellagic acid inhibit the MAO activity with both the competitive and noncompetitive type of inhibitions. Conclusions: Curcumin and ellagic acid can be considered a possible source of MAO inhibitor used in the treatment of Parkinson's and other neurological disorders. SUMMARY Monoamine oxidase (MAO) is involved in a variety of neurological disorders including Parkinson's disease (PD)Curcumin and ellagic acid inhibit the monoamine oxidase activityEllagic acid revealed more potent MAO type-B (MAO-B) inhibitory activity than curcuminKinetic studies of MAO inhibition using different concentrations of curcumin and ellagic acid were plotted as double reciprocal Lineweaver–Burk plotThe mode of inhibition of both compounds toward MAO-B is mixed (competitive and uncompetitive) type of inhibition with both the competitive and noncompetitive type of inhibitions. Abbreviations used: MAO: Monoamine oxidase

  15. Curcumin inhibits oral squamous cell carcinoma SCC-9 cells proliferation by regulating miR-9 expression

    SciTech Connect

    Xiao, Can; Wang, Lili; Zhu, Lifang; Zhang, Chenping; Zhou, Jianhua

    2014-11-28

    Highlights: • miR-9 expression level was significantly decreased in OSCC tissues. • Curcumin significantly inhibited SCC-9 cells proliferation. • miR-9 mediates the inhibition of SCC-9 proliferation by curcumin. • Curcumin suppresses Wnt/β-catenin signaling in SCC-9 cells. • miR-9 mediates the suppression of Wnt/β-catenin signaling by curcumin. - Abstract: Curcumin, a phytochemical derived from the rhizome of Curcuma longa, has shown anticancer effects against a variety of tumors. In the present study, we investigated the effects of curcumin on the miR-9 expression in oral squamous cell carcinoma (OSCC) and explored the potential relationships between miR-9 and Wnt/β-catenin pathway in curcumin-mediated OSCC inhibition in vitro. As the results shown, the expression levels of miR-9 were significantly lower in clinical OSCC specimens than those in the adjacent non-tumor tissues. Furthermore, our results indicated that curcumin inhibited OSCC cells (SCC-9 cells) proliferation through up-regulating miR-9 expression, and suppressing Wnt/β-catenin signaling by increasing the expression levels of the GSK-3β, phosphorylated GSK-3β and β-catenin, and decreasing the cyclin D1 level. Additionally, the up-regulation of miR-9 by curcumin in SCC-9 cells was significantly inhibited by delivering anti-miR-9 but not control oligonucleotides. Downregulation of miR-9 by anti-miR-9 not only attenuated the growth-suppressive effects of curcumin on SCC-9 cells, but also re-activated Wnt/β-catenin signaling that was inhibited by curcumin. Therefore, our findings would provide a new insight into the use of curcumin against OSCC in future.

  16. Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy

    PubMed Central

    Bisht, Savita; Feldmann, Georg; Soni, Sheetal; Ravi, Rajani; Karikar, Collins; Maitra, Amarnath; Maitra, Anirban

    2007-01-01

    Background Curcumin, a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa), has potent anti-cancer properties as demonstrated in a plethora of human cancer cell line and animal carcinogenesis models. Nevertheless, widespread clinical application of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility, and consequently, minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic agents like curcumin dispersible in aqueous media, thus circumventing the pitfalls of poor solubility. Results We have synthesized polymeric nanoparticle encapsulated formulation of curcumin – nanocurcumin – utilizing the micellar aggregates of cross-linked and random copolymers of N-isopropylacrylamide (NIPAAM), with N-vinyl-2-pyrrolidone (VP) and poly(ethyleneglycol)monoacrylate (PEG-A). Physico-chemical characterization of the polymeric nanoparticles by dynamic laser light scattering and transmission electron microscopy confirms a narrow size distribution in the 50 nm range. Nanocurcumin, unlike free curcumin, is readily dispersed in aqueous media. Nanocurcumin demonstrates comparable in vitro therapeutic efficacy to free curcumin against a panel of human pancreatic cancer cell lines, as assessed by cell viability and clonogenicity assays in soft agar. Further, nanocurcumin's mechanisms of action on pancreatic cancer cells mirror that of free curcumin, including induction of cellular apoptosis, blockade of nuclear factor kappa B (NFκB) activation, and downregulation of steady state levels of multiple pro-inflammatory cytokines (IL-6, IL-8, and TNFα). Conclusion Nanocurcumin provides an opportunity to expand the clinical repertoire of this efficacious agent by enabling ready aqueous dispersion. Future studies utilizing nanocurcumin are warranted in pre-clinical in vivo models of cancer and other diseases that might benefit from the effects of

  17. Curcumin Attenuates Hepatotoxicity Induced by Zinc Oxide Nanoparticles in Rats

    PubMed Central

    Khorsandi, Layasadat; Mansouri, Esrafil; Orazizadeh, Mahmoud; Jozi, Zahra

    2016-01-01

    Background: Zinc oxide nanoparticles (NZnO) are increasingly used in modern life. Most metal nanoparticles have adverse effects on the liver. Aims: To explore the protective action of curcumin (Cur) against hepatotoxicity induced by NZnO in rats. Study Design: Animal experimentation. Methods: Control group animals received normal saline, while the Cur group animals were treated with 200 mg/kg of Cur orally for 21 days. NZnO-intoxicated rats received 50 mg/kg of NZnO for 14 days by gavage method. In the NZnO+Cur group, rats were pretreated with Cur for 7 days before NZnO administration. Plasma activities of Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were measured as biomarkers of hepatotoxicity. Hepatic levels of malondialdehyde (MDA) and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured for detection of oxidative stress in liver tissue. Histological changes and apoptosis in liver tissue were studied by using Hematoxylin-eosin staining and the transferase dUTP nick end labeling (TUNEL) method. Results: NZnO induced a significant increase in plasma AST (2.8-fold), ALT (2.7-fold) and ALP (1.97-fold) activity in comparison to the control group (p<0.01). NZnO increased MDA content and reduced SOD and GPx activities. NZnO caused liver damage including centrilobular necrosis and microvesicular steatosis. The percentage of apoptosis in hepatocytes was increased in NZnO-treated rats (p<0.01). Pre-treatment of Cur significantly reduced lipid peroxidation (39%), increased SOD (156%) and GPx (26%) activities, and attenuated ALT (47%), AST (41%) and ALP (30%) activities. Pre-treatment with Cur also decreased the histology changes and apoptotic index of hepatocytes (p<0.05). Conclusion: These findings indicate that Cur effectively protects against NZnO-induced hepatotoxicity in rats. However, future studies are required to propose Cur as a potential protective agent against hepatotoxicity

  18. A new method for pH triggered curcumin release by applying poly(L-lysine) mediated nanoparticle-congregation.

    PubMed

    Patra, Digambara; Sleem, Fatima

    2013-09-17

    We introduce a novel method for encapsulation of curcumin by synthesizing microcapsule containing self-assembled nanoparticles using poly (L-lysine), trisodium citrate and silica sol. Such microcapsules can only be prepared in neutral and alkaline environment and unencapsulated curcumin can be effectively removed by simple centrifugation with encapsulation efficiency 57.34%. The particle sizes are in the range 0.7-3 μm with an effective diameter 1.05 μm. The structure of the microcapsules is dependent upon the solubility of curcumin in the solvent environment, the microcapsule are spherical when prepared in 10% acetone and bowl-shaped/conical when prepared in water suspension, however, the size of these curcumin encapsulated microcapsules remain similar. Fluorescence microscope images confirm that curcumin is predominantly concentrated within the shell wall of the capsules. Photophysical behavior of Micro-curcumin with respect to curcumin alone is evaluated. Release of curcumin is found to be triggered by pH where acidic environment trigger maximum release compared to basic and neutral conditions. Micro-curcumin is as stable as curcumin. Drug release efficiency is found to be 61.44% and the drug release profile of Micro-curcumin follow Higuchi model. It is also revealed that β-diketone group of curcumin responsible for scavenging activity is retained in the Micro-curcumin, thus suggesting applicability of such system as a poorly water soluble drug delivery vehicle. In contrast to other curcumin delivery systems, the presented method is easy, fast and does not need flow rate monitoring device. In addition poly (L-lysine) as a non-toxic and highly stable material that prevents metabolic degradation is used in the present preparation method. PMID:23998538

  19. EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent.

    PubMed

    Li, Xiaoling; Ye, Xianlong; Qi, Jianying; Fan, Rangrang; Gao, Xiang; Wu, Yunzhou; Zhou, Liangxue; Tong, Aiping; Guo, Gang

    2016-01-01

    Wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair; however, precise control over its application is necessary to reduce the side effects and achieve desired therapeutic benefits. Moreover, the extensive oxidative stress during the wound healing process generally inhibits repair of the injured tissues. Topical applications of antioxidants like curcumin (Cur) could protect tissues from oxidative damage and significantly improve tissue remodeling. To achieve much accelerated wound healing effects, we designed a novel dual drug co-loaded in situ gel-forming nanoparticle/hydrogel system (EGF-Cur-NP/H) which acted not only as a supportive matrix for the regenerative tissue, but also as a sustained drug depot for EGF and Cur. In the established excisional full-thickness wound model, EGF-Cur-NP/H treatment significantly enhanced wound closure through increasing granulation tissue formation, collagen deposition, and angiogenesis, relative to normal saline, nanoparticle/hydrogel (NP/H), Cur-NP/H, and EGF-NP/H treated groups. In conclusion, this study provides a biocompatible in situ gel-forming system for efficient topical application of EGF and Cur in the landscape of tissue repair. PMID:27574428

  20. EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent

    PubMed Central

    Li, Xiaoling; Ye, Xianlong; Qi, Jianying; Fan, Rangrang; Gao, Xiang; Wu, Yunzhou; Zhou, Liangxue; Tong, Aiping; Guo, Gang

    2016-01-01

    Wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair; however, precise control over its application is necessary to reduce the side effects and achieve desired therapeutic benefits. Moreover, the extensive oxidative stress during the wound healing process generally inhibits repair of the injured tissues. Topical applications of antioxidants like curcumin (Cur) could protect tissues from oxidative damage and significantly improve tissue remodeling. To achieve much accelerated wound healing effects, we designed a novel dual drug co-loaded in situ gel-forming nanoparticle/hydrogel system (EGF-Cur-NP/H) which acted not only as a supportive matrix for the regenerative tissue, but also as a sustained drug depot for EGF and Cur. In the established excisional full-thickness wound model, EGF-Cur-NP/H treatment significantly enhanced wound closure through increasing granulation tissue formation, collagen deposition, and angiogenesis, relative to normal saline, nanoparticle/hydrogel (NP/H), Cur-NP/H, and EGF-NP/H treated groups. In conclusion, this study provides a biocompatible in situ gel-forming system for efficient topical application of EGF and Cur in the landscape of tissue repair. PMID:27574428

  1. Curcumin inhibits AP-2γ-induced apoptosis in the human malignant testicular germ cells in vitro

    PubMed Central

    Zhou, Chang; Zhao, Xiao-meng; Li, Xiao-feng; Wang, Cheng; Zhang, Xiao-ting; Liu, Xi-zhi; Ding, Xiao-feng; Xiang, Shuang-lin; Zhang, Jian

    2013-01-01

    Aim: To investigate the effects of curcumin on proliferation and apoptosis in testicular cancer cells in vitro and to investigate its molecular mechanisms of action. Methods: NTera-2 human malignant testicular germ cell line and F9 mouse teratocarcinoma stem cell line were used. The anti-proliferative effect was examined using MTT and colony formation assays. Hoechst 33258 staining, TUNEL and Annexin V-FITC/PI staining assays were used to analyze cell apoptosis. Protein expression was examined with Western blot analysis and immunocytochemical staining. Results: Curcumin (5, 10 and 15 μmol/L) inhibited the viability of NTera-2 cells in dose- and time-dependent manners. Curcumin significantly inhibited the colony formation in both NTera-2 and F9 cells. Curcumin dose-dependently induced apoptosis of NTera-2 cells by reducing FasL expression and Bcl-2-to-Bax ratio, and activating caspase-9, -8 and -3. Furthermore, curcumin dose-dependently reduced the expression of AP transcription factor AP-2γ in NTera-2 cells, whereas the pretreatment with the proteasome inhibitor MG132 blocked both the curcumin-induced reduction of AP-2γ and antiproliferative effect. Curcumin inhibited ErbB2 expression, and decreased the phosphorylation of Akt and ERK in NTera-2 cells. Conclusion: Curcumin induces apoptosis and inhibits proliferation in NTera-2 cells via the inhibition of AP-2γ-mediated downstream cell survival signaling pathways. PMID:23685957

  2. Combination of α-Tomatine and Curcumin Inhibits Growth and Induces Apoptosis in Human Prostate Cancer Cells.

    PubMed

    Huang, Huarong; Chen, Xuan; Li, Dongli; He, Yan; Li, Yu; Du, Zhiyun; Zhang, Kun; DiPaola, Robert; Goodin, Susan; Zheng, Xi

    2015-01-01

    α-Tomatine is a glycoalkaloid found in tomatoes and curcumin is a major yellow pigment of turmeric. In the present study, the combined effect of these two compounds on prostate cancer cells was studied. Treatment of different prostate cancer cells with curcumin or α-tomatine alone resulted in growth inhibition and apoptosis in a concentration-dependent manner. Combinations of α-tomatine and curcumin synergistically inhibited the growth and induced apoptosis in prostate cancer PC-3 cells. Effects of the α-tomatine and curcumin combination were associated with synergistic inhibition of NF-κB activity and a potent decrease in the expression of its downstream gene Bcl-2 in the cells. Moreover, strong decreases in the levels of phospho-Akt and phosphor-ERK1/2 were found in PC-3 cells treated with α-tomatine and curcumin in combination. In animal experiment, SCID mice with PC-3 xenograft tumors were treated with α-tomatine and curcumin. Combination of α-tomatine and curcumin more potently inhibited the growth of PC-3 tumors than either agent alone. Results from the present study indicate that α-tomatine in combination with curcumin may be an effective strategy for inhibiting the growth of prostate cancer. PMID:26630272

  3. Combination of α-Tomatine and Curcumin Inhibits Growth and Induces Apoptosis in Human Prostate Cancer Cells

    PubMed Central

    Li, Dongli; He, Yan; Li, Yu; Du, Zhiyun; Zhang, Kun; DiPaola, Robert; Goodin, Susan; Zheng, Xi

    2015-01-01

    α-Tomatine is a glycoalkaloid found in tomatoes and curcumin is a major yellow pigment of turmeric. In the present study, the combined effect of these two compounds on prostate cancer cells was studied. Treatment of different prostate cancer cells with curcumin or α-tomatine alone resulted in growth inhibition and apoptosis in a concentration-dependent manner. Combinations of α-tomatine and curcumin synergistically inhibited the growth and induced apoptosis in prostate cancer PC-3 cells. Effects of the α-tomatine and curcumin combination were associated with synergistic inhibition of NF-κB activity and a potent decrease in the expression of its downstream gene Bcl-2 in the cells. Moreover, strong decreases in the levels of phospho-Akt and phosphor-ERK1/2 were found in PC-3 cells treated with α-tomatine and curcumin in combination. In animal experiment, SCID mice with PC-3 xenograft tumors were treated with α-tomatine and curcumin. Combination of α-tomatine and curcumin more potently inhibited the growth of PC-3 tumors than either agent alone. Results from the present study indicate that α-tomatine in combination with curcumin may be an effective strategy for inhibiting the growth of prostate cancer. PMID:26630272

  4. Curcumin analogues with high activity for inhibiting human prostate cancer cell growth and androgen receptor activation.

    PubMed

    Zhou, Dai-Ying; Ding, Ning; Du, Zhi-Yun; Cui, Xiao-Xing; Wang, Hong; Wei, Xing-Chuan; Conney, Allan H; Zhang, Kun; Zheng, Xi

    2014-09-01

    The androgen receptor (AR) has a critical role in prostate cancer development and progression. Several curcumin analogues (A10, B10, C10, E10 and F10) with different linker groups were investigated for their effects in human prostate cancer CWR‑22Rv1 and LNCaP cell lines. The ability of these compounds to inhibit testosterone (TT)‑ or dihydrotestosterone (DHT)‑induced AR activity was determined by an AR‑linked luciferase assay and by TT‑ or DHT‑induced expression of prostate specific antigen. Compounds F10 and E10 had stronger inhibitory effects on the growth of cultured CWR‑22Rv1 and LNCaP cell lines, and they also had enhanced stimulatory effects on apoptosis compared with curcumin and other curcumin analogues (A10, B10, C10) in CWR‑22Rv1 cells. E10 and F10 were more potent inhibitors of AR activity than curcumin, A10 and B10. The higher activities of E10 and F10 may be correlated with a heteroatom linker. The results indicate that one of the potential mechanisms for the anticancer effect of the curcumin analogues was inhibition of AR pathways in human prostate cancer cells. PMID:25060817

  5. The inhibition of the estrogenic effects of pesticides and environmental chemicals by curcumin and isoflavonoids.

    PubMed Central

    Verma, S P; Goldin, B R; Lin, P S

    1998-01-01

    Many environmental chemicals and pesticides have been found to be estrogenic and have been shown to stimulate the growth of estrogen receptor-positive (ER-positive) human breast cancer cells. Since it is difficult to avoid human exposure to environmental estrogens, a potentially important area of research is the development of dietary strategies to prevent the stimulated growth of breast tumors by environmental estrogens. In this context, the inhibitory action of curcumin and a combination of curcumin and isoflavonoids were studied in ER-positive human breast cancer cells (MCF-7 and T47D) and ER-negative MDA-MB-231 cells induced by the pesticide o,p'-DDT and the environmental pollutants 4-nonylphenol and 4-octylphenol. The median inhibitory concentration (IC50) for curcumin in T47D cells was 10 microM when measured at either a 48-hr or a 6-day incubation time. The IC50 value for curcumin was within the 8-10 microM range for inhibiting the growth of T47D cells induced by a 10- microM concentration each of 4-nonylphenol, 4-octylphenol, and o, p'-DDT. The IC50 for curcumin in MCF-7 cells induced by 10 microM of either o,p'-DDT, 4-octylphenol, or 4-nonylphenol were 9, 39, and >50 microM, respectively. A combination of curcumin and isoflavonoids was able to inhibit the induced growth of ER-positive cells up to 95%. For MDA-MB-231 cells, the IC50 for curcumin was 17 microM, which was reduced to 11 microM in the presence of 25 microM genistein. Curcumin and genistein induce drastic changes in the morphological shape of both ER-positive and ER-negative cells. Data presented here indicate that a mixture of curcumin and isoflavonoids is the most potent inhibitor against the growth of human breast tumor cells. These data suggest that combinations of natural plant compounds may have preventive and therapeutic applications against the growth of breast tumors induced by environmental estrogens. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9831541

  6. Polycaprolactone-based in situ implant containing curcumin-PLGA nanoparticles prepared using the multivariate technique.

    PubMed

    Kasinathan, Narayanan; Amirthalingam, Muthukumar; Reddy, Neetinkumar D; Vanthi, Meenashi B; Volety, Subrahmanyam M; Rao, Josyula Venkata

    2016-09-01

    Studies on the effect of curcumin/PLGA ratio (CPR), stabilizer (PVA) concentration, homogenization speed, homogenization time, and sonication time on mean particle size (MPS) and percentage drug encapsulation (PDE) were performed using the multivariate technique. MPS and PDE were found to be more dependent on the interaction of sonication time with the other variables. Curcumin was released in a sustained manner from curcumin-PLGA nanoparticles (CPN). CPN improved the survival rate of Ehrlich ascites carcinoma (EAC)-bearing mice and controlled the EAC-induced change in hematological parameters. Histopathology of vital organs showed that the formulation was safe. Polycaprolactone was used in preparing an in situ implant containing CPN. PMID:26121330

  7. Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin

    PubMed Central

    Limtrakul, Porn-ngarm; Anuchapreeda, Songyot; Lipigorngoson, Suwiwek; Dunn, Floyd W

    2001-01-01

    Background We investigated the chemopreventive action of dietary curcumin on 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12,0-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation in Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical scavenger, and antiinflammatory properties. It has been shown by previously reported work that TPA-induced skin tumors were inhibited by topical application of curcumin, and curcumin has been shown to inhibit a variety of biological activities of TPA. Topical application of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper reports the effects of orally administered curcumin, which was consumed as a dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding. Results Animals in which tumors had been initiated with DMBA and promoted with TPA experienced significantly fewer tumors and less tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of curcumin resulted in a significantly decreased expression of ras and fos proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence Western blotting detection system (Amersham). Conclusions Whereas earlier work demonstrated that topical application of curcumin to mouse skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the first to show that orally consumed curcumin significantly inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin. PMID:11231886

  8. Efficacy of Biodegradable Curcumin Nanoparticles in Delaying Cataract in Diabetic Rat Model

    PubMed Central

    Patil, Madhoosudan A.; Raghu, Ganugula; Balakrishna, Nagalla; Kumar, M. N. V. Ravi; Reddy, Geereddy Bhanuprakash

    2013-01-01

    Curcumin, the active principle present in the yellow spice turmeric, has been shown to exhibit various pharmacological actions such as antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Previously we have reported that dietary curcumin delays diabetes-induced cataract in rats. However, low peroral bioavailability is a major limiting factor for the success of clinical utilization of curcumin. In this study, we have administered curcumin encapsulated nanoparticles in streptozotocin (STZ) induced diabetic cataract model. Oral administration of 2 mg/day nanocurcumin was significantly more effective than curcumin in delaying diabetic cataracts in rats. The significant delay in progression of diabetic cataract by nanocurcumin is attributed to its ability to intervene the biochemical pathways of disease progression such as protein insolubilization, polyol pathway, protein glycation, crystallin distribution and oxidative stress. The enhanced performance of nanocurcumin can be attributed probably to its improved oral bioavailability. Together, the results of the present study demonstrate the potential of nanocurcumin in managing diabetic cataract. PMID:24155984

  9. Curcumin Inhibits Non-Small Cell Lung Cancer Cells Metastasis through the Adiponectin/NF-κb/MMPs Signaling Pathway

    PubMed Central

    Tsai, Jong-Rung; Liu, Po-Len; Chen, Yung-Hsiang; Chou, Shah-Hwa; Cheng, Yu-Jen; Hwang, Jhi-Jhu; Chong, Inn-Wen

    2015-01-01

    Adipose tissue is now considered as an endocrine organ involved in metabolic and inflammatory reactions. Adiponectin, a 244–amino acid peptide hormone, is associated with insulin resistance and carcinogenesis. Curcumin (diferuloylmethane) is the principal curcuminoid of the popular Indian spice, turmeric. Curcumin possesses antitumor effects, including the inhibition of neovascularization and regulation of cell cycle and apoptosis. However, the effects of adiponectin and curcumin on non-small cell lung cancer (NSCLC) remain unclear. In this study, we evaluated the expression of adiponectin in paired tumors and normal lung tissues from 77 patients with NSCLC using real-time polymerase chain reaction, western blotting, and immunohistochemistry. Kaplan–Meier survival analysis showed that patients with low adiponectin expression ratio (<1) had significantly longer survival time than those with high expression ratio (>1) (p = 0.015). Curcumin inhibited the migratory and invasive ability of A549 cells via the inhibition of adiponectin expression by blocking the adiponectin receptor 1. Curcumin treatment also inhibited the in vivo tumor growth of A549 cells and adiponectin expression. These results suggest that adiponectin can be a prognostic indicator of NSCLC. The effect of curcumin in decreasing the migratory and invasive ability of A549 cells by inhibiting adiponectin expression is probably mediated through NF-κB/MMP pathways. Curcumin could be an important potential adjuvant therapeutic agent for lung cancer in the future. PMID:26656720

  10. Curcumin Inhibits Non-Small Cell Lung Cancer Cells Metastasis through the Adiponectin/NF-κb/MMPs Signaling Pathway.

    PubMed

    Tsai, Jong-Rung; Liu, Po-Len; Chen, Yung-Hsiang; Chou, Shah-Hwa; Cheng, Yu-Jen; Hwang, Jhi-Jhu; Chong, Inn-Wen

    2015-01-01

    Adipose tissue is now considered as an endocrine organ involved in metabolic and inflammatory reactions. Adiponectin, a 244-amino acid peptide hormone, is associated with insulin resistance and carcinogenesis. Curcumin (diferuloylmethane) is the principal curcuminoid of the popular Indian spice, turmeric. Curcumin possesses antitumor effects, including the inhibition of neovascularization and regulation of cell cycle and apoptosis. However, the effects of adiponectin and curcumin on non-small cell lung cancer (NSCLC) remain unclear. In this study, we evaluated the expression of adiponectin in paired tumors and normal lung tissues from 77 patients with NSCLC using real-time polymerase chain reaction, western blotting, and immunohistochemistry. Kaplan-Meier survival analysis showed that patients with low adiponectin expression ratio (<1) had significantly longer survival time than those with high expression ratio (>1) (p = 0.015). Curcumin inhibited the migratory and invasive ability of A549 cells via the inhibition of adiponectin expression by blocking the adiponectin receptor 1. Curcumin treatment also inhibited the in vivo tumor growth of A549 cells and adiponectin expression. These results suggest that adiponectin can be a prognostic indicator of NSCLC. The effect of curcumin in decreasing the migratory and invasive ability of A549 cells by inhibiting adiponectin expression is probably mediated through NF-κB/MMP pathways. Curcumin could be an important potential adjuvant therapeutic agent for lung cancer in the future. PMID:26656720

  11. Curcumin Blocks Naproxen-Induced Gastric Antral Ulcerations through Inhibition of Lipid Peroxidation and Activation of Enzymatic Scavengers in Rats.

    PubMed

    Kim, Jeong-Hwan; Jin, Soojung; Kwon, Hyun Ju; Kim, Byung Woo

    2016-08-28

    Curcumin is a polyphenol derived from the plant Curcuma longa, which is used for the treatment of diseases associated with oxidative stress and inflammation. The present study was undertaken to determine the protective effect of curcumin against naproxen-induced gastric antral ulcerations in rats. Different doses (10, 50, and 100 mg/kg) of curcumin or vehicle (curcumin, 0 mg/kg) were pretreated for 3 days by oral gavage, and then gastric mucosal lesions were caused by 80 mg/kg naproxen applied for 3 days. Curcumin significantly inhibited the naproxen-induced gastric antral ulcer area and lipid peroxidation in a dose-dependent manner. In addition, curcumin markedly increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Specifically, 100 mg/kg curcumin completely protected the gastric mucosa against the loss in the enzyme, resulting in a drastic increase of activities of radical scavenging enzymes up to more than the level of untreated normal rats. Histological examination obviously showed that curcumin prevents naproxen-induced gastric antral ulceration as a result of direct protection of the gastric mucosa. These results suggest that curcumin blocks naproxen-induced gastric antral ulcerations through prevention of lipid peroxidation and activation of radical scavenging enzymes, and it may offer a potential remedy of gastric antral ulcerations. PMID:27197667

  12. Synthesis of mesoporous TiO2-curcumin nanoparticles for photocatalytic degradation of methylene blue dye.

    PubMed

    Abou-Gamra, Z M; Ahmed, M A

    2016-07-01

    Herein, we demonstrate a facile route for synthesis a new photocatalyst based on TiO2-curcumin nanoparticles for photodegradation of methylene blue dye under UV and visible light irradiation. The photocatalyst was prepared by sol-gel method using chitosan as biodegradable polymer. The crystalline and the nanostructure were characteristic X-ray diffraction [XRD], adsorption-desorption isotherm and high resolution transmission electron microscopy [HRTEM]. However, the optical features of the samples were investigated by a UV-visible spectrophotometer. It is obvious to notice the removal of the majority of methylene blue dye on a pure titania surface via adsorption mechanism owing to the high surface area and to the organized mesoporous nature of the solid sample. Incorporation of curcumin on titania surface changes the removal direction from adsorption to the photocatalytic pathway. Various photocatalytic experiments were performed to investigate the influence of initial dye concentration, weight of catalyst, stirring and light intensity on the photocatalytic degradation of methylene blue as primary pollutant model. Chemical oxygen demand [COD] test confirms the complete degradation of methylene blue dye. The exceptional photocatalytic reactivity of titania-curcumin nanoparticles is referred to reduction in band gap energy and to the facility of electron transfer from II* curcumin energy level to titania conduction band which increases the concentration of reactive oxygen superoxide radicals which in turn prevents the electron-hole recombination. The effect of various scavengers on the methylene blue dye degradation was investigated using ethanol, ascorbic acid and methyl viologen. The results have pointed out that O2(-) and HO(.) are considered the main active species in the degradation process. A plausible pathway and mechanism for the photocatalytic degradation of methylene blue by titania-curcumin nanoparticles were illustrated. PMID:27107333

  13. Curcumin induces apoptosis by inhibiting sarco/endoplasmic reticulum Ca2+ ATPase activity in ovarian cancer cells.

    PubMed

    Seo, Jeong-Ah; Kim, Boyun; Dhanasekaran, Danny N; Tsang, Benjamin K; Song, Yong Sang

    2016-02-01

    Aberrant increase in the expression levels of sarco/endoplasmic reticulum calcium ATPase (SERCA), which regulates Ca(2+) homeostasis, has been observed in ovarian cancers. In this study, we demonstrated that curcumin increases cytosolic Ca(2+) concentration through inhibition of SERCA activity, causing apoptosis in ovarian cancer cells but not in normal cells, including peripheral blood mononuclear cells (PBMCs) and ovarian surface epithelial cells (OSE). Curcumin induced apoptosis in ovarian cancer cells in a concentration- and time-dependent manner. Cytosolic Ca(2+) flux was evident after the curcumin treatment (15 µM). Treatment with Ca(2+) chelator reduced curcumin-induced apoptosis, confirming the possible involvement of increased cytosolic Ca(2+) concentration in this response. Basal mRNA and protein levels of SERCA2 were significantly higher in ovarian cancer cells than in OSE. SERCA activity was suppressed by curcumin, with no effect on protein expression. Forced expression of the SERCA2b gene in ovarian cancer cells prevented curcumin-induced cytosolic Ca(2+) elevation and subsequent apoptosis, supporting an important role of SERCA in curcumin-induced apoptosis of ovarian cancer cells. Taken together, inhibition of SERCA activity by curcumin disrupts the Ca(2+) homeostasis and thereby promotes apoptosis in ovarian cancer cells. PMID:26607901

  14. Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma.

    PubMed

    Zhang, Issan; Cui, Yiming; Amiri, Abdolali; Ding, Yidan; Campbell, Robert E; Maysinger, Dusica

    2016-03-01

    Increased lipid droplet number and fatty acid synthesis allow glioblastoma multiforme, the most common and aggressive type of brain cancer, to withstand accelerated metabolic rates and resist therapeutic treatments. Lipid droplets are postulated to sequester hydrophobic therapeutic agents, thereby reducing drug effectiveness. We hypothesized that the inhibition of lipid droplet accumulation in glioblastoma cells using pyrrolidine-2, a cytoplasmic phospholipase A2 alpha inhibitor, can sensitize cancer cells to the killing effect of curcumin, a promising anticancer agent isolated from the turmeric spice. We observed that curcumin localized in the lipid droplets of human U251N glioblastoma cells. Reduction of lipid droplet number using pyrrolidine-2 drastically enhanced the therapeutic effect of curcumin in both 2D and 3D glioblastoma cell models. The mode of cell death involved was found to be mediated by caspase-3. Comparatively, the current clinical chemotherapeutic standard, temozolomide, was significantly less effective in inducing glioblastoma cell death. Together, our results suggest that the inhibition of lipid droplet accumulation is an effective way to enhance the chemotherapeutic effect of curcumin against glioblastoma multiforme. PMID:26763536

  15. Curcumin inhibits aerobic glycolysis in hepatic stellate cells associated with activation of adenosine monophosphate-activated protein kinase.

    PubMed

    Lian, Naqi; Jin, Huanhuan; Zhang, Feng; Wu, Li; Shao, Jiangjuan; Lu, Yin; Zheng, Shizhong

    2016-07-01

    Activation of hepatic stellate cells (HSCs) is characterized by expression of extracellular matrix and loss of adipogenic phenotype during liver fibrogenesis. Emerging evidence suggests that HSCs adopt aerobic glycolysis during activation. The present work aimed at investigating whether the anti-fibrogenic effects of curcumin was associated with interfering with glycolysis in HSCs. Primary rat HSCs were cultured in vitro. We demonstrated that inhibition of glycolysis by 2-deoxyglucose or galloflavin reduced the expression of α-smooth muscle actin (α-SMA) and α1(I)procollagen at both mRNA and protein levels, and increased the intracellular lipid contents and upregulated the gene and protein expression of adipogenic transcription factors C/EBPα and PPAR-γ in HSCs. Curcumin at 20 μM produced similar effects. Moreover, curcumin decreased the expression of hexokinase (HK), phosphofructokinase-2 (PFK2), and glucose transporter 4 (glut4), three key glycolytic parameters, at both mRNA and protein levels. Curcumin also reduced lactate production concentration-dependently in HSCs. Furthermore, curcumin increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), but AMPK inhibitor BML-275 significantly abolished the curcumin downregulation of HK, PFK2, and glut4. In addition, curcumin inhibition of α-SMA and α1(I)procollagen was rescued by BML-275, and curcumin upregulation of C/EBPα and PPAR-γ was abrogated by BML-275. These results collectively indicated that curcumin inhibited glycolysis in an AMPK activation-dependent manner in HSCs. We revealed a novel mechanism for curcumin suppression of HSC activation implicated in antifibrotic therapy. © 2016 IUBMB Life, 68(7):589-596, 2016. PMID:27278959

  16. Polymer-Coated Magnetic Nanoparticles for Curcumin Delivery to Cancer Cells.

    PubMed

    Mancarella, Serena; Greco, Valentina; Baldassarre, Francesca; Vergara, Daniele; Maffia, Michele; Leporatti, Stefano

    2015-10-01

    The new goal of anticancer agent research is the screening of natural origin drugs with lower systemic adverse effects than synthetic compounds. Here, we focus on curcumin, an important polyphenolic pigment classically used as spice in the Indian cuisine. The molecule has high pleiotropic activities including strong antioxidant and anti-inflammatory properties. However, its clinical potential is limited due its low solubility and bioavailability. We have developed a layer by layer functionalization of Fe3 O4 nanoparticles (nano-Fe3 O4 ) by coating biodegradable polyelectrolyte multilayers such as Dextran (DXS) and Poly(l-lysine) (PLL). Physico-chemical studies were performed to obtain a high upload of curcumin in Fe3 O4 nanoparticles. Nano-Fe3 O4 were then tested against an ovarian cancer cell line, SKOV-3, to demonstrate their therapeutic efficacy. PMID:26085082

  17. Curcumin inhibits development and cell adhesion in Dictyostelium discoideum: Implications for YakA signaling and GST enzyme function.

    PubMed

    Garige, Mamatha; Walters, Eric

    2015-11-13

    The molecular basis for nutraceutical properties of the polyphenol curcumin (Curcuma longa, Turmeric) is complex, affecting multiple factors that regulate cell signaling and homeostasis. Here, we report the effect of curcumin on cellular and developmental mechanisms in the eukaryotic model, Dictyostelium discoideum. Dictyostelium proliferation was inhibited in the presence of curcumin, which also suppressed the prestarvation marker, discoidin I, members of the yakA-mediated developmental signaling pathway, and expression of the extracellular matrix/cell adhesion proteins (DdCAD and csA). This resulted in delayed chemotaxis, adhesion, and development of the organism. In contrast to the inhibitory effects on developmental genes, curcumin induced gstA gene expression, overall GST activity, and generated production of reactive oxygen species. These studies expand our knowledge of developmental and biochemical signaling influenced by curcumin, and lends greater consideration of GST enzyme function in eukaryotic cell signaling, development, and differentiation. PMID:26449461

  18. Nanoparticle Self-Assembled Grain Like Curcumin Conjugated ZnO: Curcumin Conjugation Enhances Removal of Perylene, Fluoranthene, and Chrysene by ZnO

    NASA Astrophysics Data System (ADS)

    Moussawi, Rasha N.; Patra, Digambara

    2016-04-01

    Curcumin conjugated ZnO, referred as Zn(cur)O, nanostructures have been successfully synthesized, these sub-micro grain-like structures are actually self-assemblies of individual needle-shaped nanoparticles. The nanostructures as synthesized possess the wurtzite hexagonal crystal structure of ZnO and exhibit very good crystalline quality. FT-Raman and TGA analysis establish that Zn(cur)O is different from curcumin anchored ZnO (ZnO@cur), which is prepared by physically adsorbing curcumin on ZnO surfaces. Chemically Zn(cur)O is more stable than ZnO@cur. Diffuse reflectance spectroscopy indicates Zn(cur)O have more impurities compared to ZnO@cur. The solid-state photoluminescence of Zn(cur)O has been investigated, which demonstrates that increase of curcumin concentration in Zn(cur)O suppresses visible emission of ZnO prepared through the same method, this implies filling ZnO defects by curcumin. However, at excitation wavelength 425 nm the emission is dominated by fluorescence from curcumin. The study reveals that Zn(cur)O can remove to a far extent high concentrations of perylene, fluoranthene, and chrysene faster than ZnO. The removal depends on the extent of curcumin conjugation and is found to be faster for PAHs having smaller number of aromatic rings, particularly, it is exceptional for fluoranthene with 93% removal after 10 minutes in the present conditions. The high rate of removal is related to photo-degradation and a mechanism has been proposed.

  19. Nanoparticle Self-Assembled Grain Like Curcumin Conjugated ZnO: Curcumin Conjugation Enhances Removal of Perylene, Fluoranthene, and Chrysene by ZnO.

    PubMed

    Moussawi, Rasha N; Patra, Digambara

    2016-01-01

    Curcumin conjugated ZnO, referred as Zn(cur)O, nanostructures have been successfully synthesized, these sub-micro grain-like structures are actually self-assemblies of individual needle-shaped nanoparticles. The nanostructures as synthesized possess the wurtzite hexagonal crystal structure of ZnO and exhibit very good crystalline quality. FT-Raman and TGA analysis establish that Zn(cur)O is different from curcumin anchored ZnO (ZnO@cur), which is prepared by physically adsorbing curcumin on ZnO surfaces. Chemically Zn(cur)O is more stable than ZnO@cur. Diffuse reflectance spectroscopy indicates Zn(cur)O have more impurities compared to ZnO@cur. The solid-state photoluminescence of Zn(cur)O has been investigated, which demonstrates that increase of curcumin concentration in Zn(cur)O suppresses visible emission of ZnO prepared through the same method, this implies filling ZnO defects by curcumin. However, at excitation wavelength 425 nm the emission is dominated by fluorescence from curcumin. The study reveals that Zn(cur)O can remove to a far extent high concentrations of perylene, fluoranthene, and chrysene faster than ZnO. The removal depends on the extent of curcumin conjugation and is found to be faster for PAHs having smaller number of aromatic rings, particularly, it is exceptional for fluoranthene with 93% removal after 10 minutes in the present conditions. The high rate of removal is related to photo-degradation and a mechanism has been proposed. PMID:27080002

  20. Nanoparticle Self-Assembled Grain Like Curcumin Conjugated ZnO: Curcumin Conjugation Enhances Removal of Perylene, Fluoranthene, and Chrysene by ZnO

    PubMed Central

    Moussawi, Rasha N.; Patra, Digambara

    2016-01-01

    Curcumin conjugated ZnO, referred as Zn(cur)O, nanostructures have been successfully synthesized, these sub-micro grain-like structures are actually self-assemblies of individual needle-shaped nanoparticles. The nanostructures as synthesized possess the wurtzite hexagonal crystal structure of ZnO and exhibit very good crystalline quality. FT-Raman and TGA analysis establish that Zn(cur)O is different from curcumin anchored ZnO (ZnO@cur), which is prepared by physically adsorbing curcumin on ZnO surfaces. Chemically Zn(cur)O is more stable than ZnO@cur. Diffuse reflectance spectroscopy indicates Zn(cur)O have more impurities compared to ZnO@cur. The solid-state photoluminescence of Zn(cur)O has been investigated, which demonstrates that increase of curcumin concentration in Zn(cur)O suppresses visible emission of ZnO prepared through the same method, this implies filling ZnO defects by curcumin. However, at excitation wavelength 425 nm the emission is dominated by fluorescence from curcumin. The study reveals that Zn(cur)O can remove to a far extent high concentrations of perylene, fluoranthene, and chrysene faster than ZnO. The removal depends on the extent of curcumin conjugation and is found to be faster for PAHs having smaller number of aromatic rings, particularly, it is exceptional for fluoranthene with 93% removal after 10 minutes in the present conditions. The high rate of removal is related to photo-degradation and a mechanism has been proposed. PMID:27080002

  1. Curcumin Inhibits Prostate Cancer Bone Metastasis by Up-Regulating Bone Morphogenic Protein-7 in Vivo

    PubMed Central

    Dorai, Thambi; Diouri, Janane; O'Shea, Orla; Doty, Stephen B.

    2014-01-01

    A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-β signaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP- 7). This enhancement of BMP-7 in the context of TGF-βin the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regu- lated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-βsignaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic

  2. Curcumin Inhibits Prostate Cancer Bone Metastasis by Up-Regulating Bone Morphogenic Protein-7 in Vivo.

    PubMed

    Dorai, Thambi; Diouri, Janane; O'Shea, Orla; Doty, Stephen B

    2014-04-01

    A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-β signaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP- 7). This enhancement of BMP-7 in the context of TGF-βin the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regu- lated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-βsignaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic

  3. Suppressing the cytotoxicity of CuO nanoparticles by uptake of curcumin/BSA particles.

    PubMed

    Zhang, Wenjing; Jiang, Pengfei; Chen, Ying; Luo, Peihua; Li, Guanqun; Zheng, Botuo; Chen, Wei; Mao, Zhengwei; Gao, Changyou

    2016-05-01

    The adverse effects of metal-based nanoparticles on human beings and the environment have received extensive attention recently. It is urgently required to develop a simple and effective method to suppress the toxicity of metal-based nanomaterials. In this study, a hydrophobic antioxidant and a chelation agent curcumin (CUR) were encapsulated into bovine serum albumin (BSA) particles by a simple co-precipitation method, and followed by glutaraldehyde cross-linking. The CUR/BSA particles had an average size of 300 nm in diameter with a negatively charged surface and sustained curcumin release properties. The cellular uptake and cytotoxicity of CUR/BSA particles were followed on A549 cells, HepG2 cells and RAW264.7 cells. The CUR/BSA particles had higher intracellular accumulation and lower cytotoxicity compared with the free curcumin at the same drug concentration. The CUR/BSA particles could suppress the cytotoxicity generated by CuO nanoparticles as a result of decrease of both the intracellular reactive oxygen species (ROS) level and Cu(2+) concentration, while the free curcumin did not show any obvious detoxicating effect. The detoxicating effects of CUR/BSA particles were further studied in an intratracheal instillation model in vivo, demonstrating significant reduction of toxicity and inflammatory response in rat lungs induced by CuO nanoparticles. The concept-proving study demonstrates the potential of the CUR/BSA particles in suppressing cytotoxicity of metal-based nanomaterials, which is a paramount requirement for the safe application of nanotechnology. PMID:27098928

  4. Suppressing the cytotoxicity of CuO nanoparticles by uptake of curcumin/BSA particles

    NASA Astrophysics Data System (ADS)

    Zhang, Wenjing; Jiang, Pengfei; Chen, Ying; Luo, Peihua; Li, Guanqun; Zheng, Botuo; Chen, Wei; Mao, Zhengwei; Gao, Changyou

    2016-05-01

    The adverse effects of metal-based nanoparticles on human beings and the environment have received extensive attention recently. It is urgently required to develop a simple and effective method to suppress the toxicity of metal-based nanomaterials. In this study, a hydrophobic antioxidant and a chelation agent curcumin (CUR) were encapsulated into bovine serum albumin (BSA) particles by a simple co-precipitation method, and followed by glutaraldehyde cross-linking. The CUR/BSA particles had an average size of 300 nm in diameter with a negatively charged surface and sustained curcumin release properties. The cellular uptake and cytotoxicity of CUR/BSA particles were followed on A549 cells, HepG2 cells and RAW264.7 cells. The CUR/BSA particles had higher intracellular accumulation and lower cytotoxicity compared with the free curcumin at the same drug concentration. The CUR/BSA particles could suppress the cytotoxicity generated by CuO nanoparticles as a result of decrease of both the intracellular reactive oxygen species (ROS) level and Cu2+ concentration, while the free curcumin did not show any obvious detoxicating effect. The detoxicating effects of CUR/BSA particles were further studied in an intratracheal instillation model in vivo, demonstrating significant reduction of toxicity and inflammatory response in rat lungs induced by CuO nanoparticles. The concept-proving study demonstrates the potential of the CUR/BSA particles in suppressing cytotoxicity of metal-based nanomaterials, which is a paramount requirement for the safe application of nanotechnology.

  5. Stronger proteasomal inhibition and higher CHOP induction are responsible for more effective induction of paraptosis by dimethoxycurcumin than curcumin.

    PubMed

    Yoon, M J; Kang, Y J; Lee, J A; Kim, I Y; Kim, M A; Lee, Y S; Park, J H; Lee, B Y; Kim, I A; Kim, H S; Kim, S-A; Yoon, A-R; Yun, C-O; Kim, E-Y; Lee, K; Choi, K S

    2014-01-01

    Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells. PMID:24625971

  6. Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of Mycobacterium tuberculosis

    PubMed Central

    Baldwin, Patrick R.; Reeves, Analise Z.; Powell, Kimberly R.; Napier, Ruth J.; Swimm, Alyson I.; Sun, Aiming; Giesler, Kyle; Bommarius, Bettina; Shinnick, Thomas M.; Snyder, James P.; Liotta, Dennis C.; Kalman, Daniel

    2016-01-01

    Tuberculosis (TB) is a major public health concern worldwide with over 2 billion people currently infected. The rise of strains of Mycobacterium tuberculosis (Mtb) that are resistant to some or all first and second line antibiotics, including multidrug-resistant (MDR), extensively drug resistant (XDR) and totally drug resistant (TDR) strains, is of particular concern and new anti-TB drugs are urgently needed. Curcumin, a natural product used in traditional medicine in India, exhibits anti-microbial activity that includes Mtb, however it is relatively unstable and suffers from poor bioavailability. To improve activity and bioavailability, mono-carbonyl analogs of curcumin were synthesized and screened for their capacity to inhibit the growth of Mtb and the related Mycobacterium marinum (Mm). Using disk diffusion and liquid culture assays, we found several analogs that inhibit in vitro growth of Mm and Mtb, including rifampicin-resistant strains. Structure activity analysis of the analogs indicated that Michael acceptor properties are critical for inhibitory activity. However, no synergistic effects were evident between the monocarbonyl analogs and rifampicin on inhibiting growth. Together, these data provide a structural basis for the development of analogs of curcumin with pronounced anti-mycobacterial activity and provide a roadmap to develop additional structural analogs that exhibit more favorable interactions with other anti-TB drugs. PMID:25618016

  7. Validation of an Ultraviolet-visible (UV-Vis) technique for the quantitative determination of curcumin in poly(L-lactic acid) nanoparticles.

    PubMed

    Silva-Buzanello, Rosana Aparecida da; Ferro, Ana Caroline; Bona, Evandro; Cardozo-Filho, Lúcio; Araújo, Pedro Henrique Hermes de; Leimann, Fernanda Vitória; Gonçalves, Odinei Hess

    2015-04-01

    Curcumin is a natural yellow-orange pigment extracted from turmeric and is a potential substitute of health-dangerous artificial dyes. Nanoencapsulation in biodegradable polymers is a promising alternative to improve curcumin stability and water solubility but curcumin concentration inside the nanoparticles must be precisely known. A reliable method to determine the actual curcumin concentration must be validated since the validation procedures warrant that the method is adequate and sufficient for the specific application involved. This work describes the validation parameters given by the International Conference on Harmonisation (ICH) guidelines to adopt an analytical method based on Ultraviolet-visible spectroscopy for the quantitative determination of curcumin encapsulated in poly(l-lactic acid) nanoparticles. This method was validated in respect to linearity, detection limit, quantification limit, accuracy and precision. Studies on the analytical procedure validation warranted safety in final results obtained for the curcumin concentration in the nanoparticles. PMID:25442529

  8. Curcumin serves as a human kv1.3 blocker to inhibit effector memory T lymphocyte activities.

    PubMed

    Lian, Yi-Tian; Yang, Xiao-Fang; Wang, Zhao-Hui; Yang, Yong; Yang, Ying; Shu, Yan-Wen; Cheng, Long-Xian; Liu, Kun

    2013-09-01

    Curcumin, the principal active component of turmeric, has long been used to treat various diseases in India and China. Recent studies show that curcumin can serve as a therapeutic agent for autoimmune diseases via a variety of mechanisms. Effector memory T cells (T(EM), CCR7⁻ CD45RO⁺ T lymphocyte) have been demonstrated to play a crucial role in the pathogenesis of T cell-mediated autoimmune diseases, such as multiple sclerosis (MS) or rheumatoid arthritis (RA). Kv1.3 channels are predominantly expressed in T(EM) cells and control T(EM) activities. In the present study, we examined the effect of curcumin on human Kv1.3 (hKv1.3) channels stably expressed in HEK-293 cells and its ability to inhibit proliferation and cytokine secretion of T(EM) cells isolated from patients with MS or RA. Curcumin exhibited a direct blockage of hKv1.3 channels in a time-dependent and concentration-dependent manner. Moreover, the activation curve was shifted to a more positive potential, which was consistent with an open-channel blockade. Paralleling hKv1.3 inhibition, curcumin significantly inhibited proliferation and interferon-γ secretion of T(EM) cells. Our findings demonstrate that curcumin is able to inhibit proliferation and proinflammatory cytokine secretion of T(EM) cells probably through inhibition of hKv1.3 channels, which contributes to the potency of curcumin for the treatment of autoimmune diseases. This is probably one of pharmacological mechanisms of curcumin used to treat autoimmune diseases. PMID:23132777

  9. Curcumin inhibits hypoxia-induced epithelial‑mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway.

    PubMed

    Cao, Lei; Xiao, Xue; Lei, Jianjun; Duan, Wanxing; Ma, Qingyong; Li, Wei

    2016-06-01

    Hypoxic microenvironment, a common feature of pancreatic cancer, is associated with tumor proliferation, metastasis and epithelial-mesenchymal transition (EMT) changes. In recent years, many natural agents, including curcumin, have been proven to possess the ability to inhibit the progression of pancreatic cancer. However, whether curcumin is able to suppress hypoxia-induced pancreatic cancer progression and the underlying mechanisms are still not fully elucidated. The aim of the present study was to evaluate whether curcumin affects hypoxia-induced EMT and the activation of Hh signaling pathway in pancreatic cancer. The human pancreatic cancer cell line Panc-1, was treated with hypoxic condition and curcumin. Cell proliferation was assessed by the MTT assay. Wound healing assay and transwell invasion assay were used to detect the migratory and invasive activity of cancer cells. The EMT-related factors, E-cadherin, N-cadherin, vimentin were detected by QT-PCR, western blot analysis and immunofluorescence staining. The Hh signaling-related factors, SHH, SMO and GLI1 were detected by western blot analysis. The results of present study showed that curcumin could not only inhibit the hypoxia-induced cell proliferation, migration and invasion in pancreatic cancer, but also mediate the expression of EMT-related factors. In addition, curcumin remarkably inhibited hypoxia-mediated activation of Hh signaling pathway. Taken together, these data indicate that curcumin plays an important role in suppressing hypoxia-induced pancreatic cancer metastasis by inhibiting the Hh signaling pathway. Curcumin might be a potential candidate for chemoprevention of this severe disease. PMID:27035865

  10. Single step synthesis, characterization and applications of curcumin functionalized iron oxide magnetic nanoparticles.

    PubMed

    Bhandari, Rohit; Gupta, Prachi; Dziubla, Thomas; Hilt, J Zach

    2016-10-01

    Magnetic iron oxide nanoparticles have been well known for their applications in magnetic resonance imaging (MRI), hyperthermia, targeted drug delivery, etc. The surface modification of these magnetic nanoparticles has been explored extensively to achieve functionalized materials with potential application in biomedical, environmental and catalysis field. Herein, we report a novel and versatile single step methodology for developing curcumin functionalized magnetic Fe3O4 nanoparticles without any additional linkers, using a simple coprecipitation technique. The magnetic nanoparticles (MNPs) were characterized using transmission electron microscopy, X-ray diffraction, fourier transform infrared spectroscopy and thermogravimetric analysis. The developed MNPs were employed in a cellular application for protection against an inflammatory agent, a polychlorinated biphenyl (PCB) molecule. PMID:27287099

  11. In Silico Inhibition Studies of Jun-Fos-DNA Complex Formation by Curcumin Derivatives

    PubMed Central

    Kumar, Anil; Bora, Utpal

    2012-01-01

    Activator protein-1 (AP1) is a transcription factor that consists of the Jun and Fos family proteins. It regulates gene expression in response to a variety of stimuli and controls cellular processes including proliferation, transformation, inflammation, and innate immune responses. AP1 binds specifically to 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive element 5′-TGAG/CTCA-3′ (AP1 site). It has been found constitutively active in breast, ovarian, cervical, and lung cancers. Numerous studies have shown that inhibition of AP1 could be a promising strategy for cancer therapeutic applications. The present in silico study provides insights into the inhibition of Jun-Fos-DNA complex formation by curcumin derivatives. These derivatives interact with the amino acid residues like Arg155 and Arg158 which play a key role in binding of Jun-Fos complex to DNA (AP1 site). Ala151, Ala275, Leu283, and Ile286 were the residues present at binding site which could contribute to hydrophobic contacts with inhibitor molecules. Curcumin sulphate was predicted to be the most potent inhibitor amongst all the natural curcumin derivatives docked. PMID:25374685

  12. Curcumin inhibits intracellular fatty acid synthase and induces apoptosis in human breast cancer MDA-MB-231 cells.

    PubMed

    Fan, Huijin; Liang, Yan; Jiang, Bing; Li, Xiabing; Xun, Hang; Sun, Jia; He, Wei; Lau, Hay Tong; Ma, Xiaofeng

    2016-05-01

    High levels of fatty acid synthase (FAS) expression have been found in many tumors, including prostate, breast, and ovarian cancers, and inhibition of FAS has been reported to obstruct tumor growth in vitro and in vivo. Curcumin is one of the major active ingredients of Curcuma longa, which has been proven to inhibit the growth of cancer cells. In the present study, we investigated the potential activity of curcumin as a FAS inhibitor for chemoprevention of breast cancer. As a result, curcumin induced human breast cancer MDA-MB-231 cell apoptosis with the half-inhibitory concentration value of 3.63 ± 0.26 µg/ml, and blocked FAS activity, expression and mRNA level in a dose-dependent manner. Curcumin also regulated B-cell lymphoma 2 (Bcl-2), Bax and p-Akt protein expression in MDA-MB-231 cells. Moreover, FAS knockdown showed similar effect as curcumin. All these results suggested that curcumin may induce cell apoptosis via inhibiting FAS. PMID:26985864

  13. Curcumin induces autophagy, inhibits proliferation and invasion by downregulating AKT/mTOR signaling pathway in human melanoma cells.

    PubMed

    Zhao, Guangming; Han, Xiaodong; Zheng, Siwen; Li, Zhen; Sha, Yang; Ni, Jing; Sun, Zhe; Qiao, Song; Song, Zhiqi

    2016-02-01

    Melanoma is the foremost malignant cutaneous cancer and it is extremely resistant to chemotherapy and radiotherapy. Curcumin is an active component of turmeric, the yellow spice derived from the rhizome of Curcuma longa, and is widely known for its anti-inflammatory and anti-cancerogenic properties. Several recent studies suggest that curcumin induces apoptosis by modulating multiple signaling pathways to exert its anticancer effect. In the present study, we investigated the effect of curcumin on the viability, invasion potential, cell cycle, autophagy and the AKT, mTOR, P70S6K proteins of AKT/mTOR signaling pathway in human melanoma A375 and C8161 cell lines in vitro and in an in vivo tumorigenesis model. Curcumin effectively inhibited the proliferation of melanoma cells in vitro and in vivo. It suppressed cell invasion, arrested the cancer cells at G2/M phase of the cell cycle, and induced autophagy. Furthermore, curcumin suppressed the activation of AKT, mTOR and P70S6K proteins. Curcumin, therefore, is a potent suppressor of cell viability and invasion, and simultaneously an inducer of autophagy in A375 and C8161 cells. Accordingly, curcumin could be a novel therapeutic candidate for the management of melanoma. PMID:26573768

  14. Preparation and characterization of albumin nanoparticles encapsulating curcumin intended for the treatment of breast cancer

    PubMed Central

    Jithan, AV; Madhavi, K; Madhavi, M; Prabhakar, K

    2011-01-01

    Introduction: For the real-time clinical utilization of curcumin (an ayurvedic natural product) to treat breast cancer, its dissolution, rate limited solubility, poor tissue absorption, and extensive in vivo metabolism that leads to its poor systemic bioavailability should be overcome. A polymer-based nanoparticle formulation using bovine serum albumin can increase its aqueous solubility and can achieve protected, sustained, and targeted therapy in breast cancer. Materials and Methods: Desolvation technique was optimized for the preparation of albumin nanoparticles. Particle size, drug release, encapsulation efficiency, drug polymer interaction were the in vitro properties that were determined. Cell culture studies, in vivo pharmacokinetics in rats were used for biological characterization of the formulation. Results: The formulations were successfully prepared using 1:1, 1:2, 1:3, 1:4 drug: polymer ratios and the percent entrapment was found to be 74.76%, 91.01%, 85.36%, 86.42%, respectively, and particle size determined by zetasizer was found to be 225.1, 223.5, 226.3, 228.7 nm, respectively, and in vitro release was sustained for at least one month with drug release of 75.74%, 65.97%, 64.42%, 54%, respectively. The dissolution rate and aqueous solubility of curcumin was enhanced with this formulation. Fourier transform infrared spectroscopy (FTIR) studies demonstrated that the drug was not changed in the formulation during the fabrication process. The proliferation assays in MDA-MB-231 tumor cell lines indicated more effectiveness of the formulation compared to its solution form. In rats, albumin nanoparticles sustained drug release, demonstrated more bioavailability, improved pharmacokinetic properties, and enhanced tissue targetability of the drug. Conclusions: An effective curcumin-albumin nanoparticle formulation was successfully developed using a desolvation technique. PMID:23071931

  15. Electrospun composite nanofibers of poly vinyl pyrrolidone and zinc oxide nanoparticles modified carbon paste electrode for electrochemical detection of curcumin.

    PubMed

    Afzali, Moslem; Mostafavi, Ali; Shamspur, Tayebeh

    2016-11-01

    A simple and novel ferrocene-nanofiber carbon paste electrode was developed to determine curcumin in a phosphate buffer solution at pH=8. ZnO nanoparticles were produced via a sonochemical process and composite nanofibers of PVP/ZnO were prepared by electrospinning. The characterization was performed by SEM, XRD and IR. The results suggest that the electrospun composite nanofibers having a large surface area promote electron transfer for the oxidation of curcumin and hence the FCNFCPE exhibits high electrocatalytic activity and performs well in regard to the oxidation of curcumin. The proposed method was successfully applied for measurement of curcumin in urine and turmeric as real samples. PMID:27524081

  16. Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling

    SciTech Connect

    Forward, Nicholas A.; Conrad, David M.; Power Coombs, Melanie R.; Doucette, Carolyn D.; Furlong, Suzanne J.; Lin, Tong-Jun; Hoskin, David W.

    2011-04-22

    Highlights: {yields} Curcumin inhibits CD4{sup +} T-lymphocyte proliferation. {yields} Curcumin inhibits interleukin-2 (IL-2) synthesis and CD25 expression by CD4{sup +} T-lymphocytes. {yields} Curcumin interferes with IL-2 receptor signaling by inhibiting JAK3 and STAT5 phosphorylation. {yields} IL-2-dependent regulatory T-lymphocyte function and Foxp3 expression is downregulated by curcumin. -- Abstract: Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4{sup +} T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 ({alpha} chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca{sup 2+} release to inhibit I{kappa}B phosphorylation, which is required for nuclear translocation of the transcription factor NF{kappa}B. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4{sup +}CD25{sup +} regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling.

  17. Synthesis and Characterization of Curcumin-Functionalized HP-β-CD-Modified GoldMag Nanoparticles as Drug Delivery Agents.

    PubMed

    Lian, Ting; Peng, Mingli; Vermorken, Alphons J M; Jin, Yanyan; Luo, Zhiyi; Van de Ven, Wim J M; Wan, Yinsheng; Hou, Peng; Cui, Yali

    2016-06-01

    Curcumin, a polyphenol extracted from turmeric (Curcuma longa), has emerged as a potent multimodal cancer-preventing agent. It may attenuate the spread of cancer and render chemotherapy more effective. However, curcumin is neither well absorbed nor well retained in the blood, resulting in low efficacy. In an attempt to enhance the potency and to improve the bioavailability of curcumin, new delivery agents, hydroxypropyl-beta-cyclodextrin (HP-β-CD)-modified GoldMag nanoparticles (CD-GMNs) were designed and synthesized to incorporate curcumin. The CD-GMNs were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Thermo-gravimetric Analysis (TGA), X-ray Diffraction (XRD), Dynamic Light Scattering measurements (DLS), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM) analyses. For the magnetic carrier of CD-GMNs, the content of HP-β-CD was 26.9 wt%. CD-GMNs have a saturation magnetization of 22.7 emu/g with an average hydrodynamic diameter of 80 nm. The curcumin loading, encapsulation efficiency and releasing properties in vitro were also investigated. The results showed that the drug encapsulation ratio was 88% and the maximum curcumin loading capacity of CD-GMNs was 660 μg/5 mg. In vitro drug release studies showed a controlled and pH-sensitive curcumin release over a period of one week. Collectively, our data suggest that HP-β-CD-modified GoldMag nanoparticles can be considered to form a promising delivery system for curcumin to tumor sites. Targeting can be achieved by the combined effects of the application of an external magnetic field and the effect on drug release of lower pH values often found in the tumor microenvironment. PMID:27427699

  18. Folate Decorated Dual Drug Loaded Nanoparticle: Role of Curcumin in Enhancing Therapeutic Potential of Nutlin-3a by Reversing Multidrug Resistance

    PubMed Central

    Das, Manasi; Sahoo, Sanjeeb K.

    2012-01-01

    Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP) is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR) by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs) surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined) and single or dual drug loaded nanoparticles (unconjugated/folate conjugated). The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs) over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype. PMID:22470431

  19. Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.

    PubMed

    Das, Manasi; Sahoo, Sanjeeb K

    2012-01-01

    Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP) is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR) by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs) surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined) and single or dual drug loaded nanoparticles (unconjugated/folate conjugated). The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs) over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype. PMID:22470431

  20. Curcumin Nanoparticles Ameliorate ICAM-1 Expression in TNF-α-Treated Lung Epithelial Cells through p47 phox and MAPKs/AP-1 Pathways

    PubMed Central

    Yang, Chuen-Mao; Liang, Chan-Jung; Lin, Chun-Ching; Chiang, Yao-Chang; Lee, Hui-Chun; Ko, Horng-Huey; Lee, Chiang-Wen

    2013-01-01

    Upregulation of intercellular adhesion molecule-1 (ICAM-1) involves adhesions between both circulating and resident leukocytes and the human lung epithelial cells during lung inflammatory reactions. We have previously demonstrated that curcumin-loaded polyvinylpyrrolidone nanoparticles (CURN) improve the anti-inflammatory and anti-oxidative properties of curcumin in hepatocytes. In this study, we focused on the effects of CURN on the expression of ICAM-1 in TNF-α-treated lung epithelial cells and compared these to the effects of curcumin water preparation (CURH). TNF-αinduced ICAM-1 expression, ROS production, and cell-cell adhesion were significantly attenuated by the pretreatment with antioxidants (DPI, APO, or NAC) and CURN, but not by CURH, as revealed by western blot analysis, RT-PCR, promoter assay, and ROS detection and adhesion assay. In addition, treatment of TNF-α-treated cells with CURN and antioxidants also resulted in an inhibition of activation of p47 phox and phosphorylation of MAPKs, as compared to that using CURH. Our findings also suggest that phosphorylation of MAPKs may eventually lead to the activation of transcription factors. We also observed that the effects of TNF-α treatment for 30 min, which includes a significant increase in the binding activity of AP-1 and phosphorylation of c-jun and c-fos genes, were reduced by CURN treatment. In vivo studies have revealed that CURN improved the anti-inflammation activities of CURH in the lung epithelial cells of TNF-α-treated mice. Our results indicate that curcumin-loaded polyvinylpyrrolidone nanoparticles may potentially serve as an anti-inflammatory drug for the treatment of respiratory diseases. PMID:23671702

  1. Inhibition of biofilm development of uropathogens by curcumin - an anti-quorum sensing agent from Curcuma longa.

    PubMed

    Packiavathy, Issac Abraham Sybiya Vasantha; Priya, Selvam; Pandian, Shunmugiah Karutha; Ravi, Arumugam Veera

    2014-04-01

    Urinary tract infection is caused primarily by the quorum sensing (QS)-dependent biofilm forming ability of uropathogens. In the present investigation, an anti-quorum sensing (anti-QS) agent curcumin from Curcuma longa (turmeric) was shown to inhibit the biofilm formation of uropathogens, such as Escherichia coli, Pseudomonas aeruginosa PAO1, Proteus mirabilis and Serratia marcescens, possibly by interfering with their QS systems. The antibiofilm potential of curcumin on uropathogens as well as its efficacy in disturbing the mature biofilms was examined under light microscope and confocal laser scanning microscope. The treatment with curcumin was also found to attenuate the QS-dependent factors, such as exopolysaccharide production, alginate production, swimming and swarming motility of uropathogens. Furthermore, it was documented that curcumin enhanced the susceptibility of a marker strain and uropathogens to conventional antibiotics. PMID:24262582

  2. Curcumin Promotes Cell Cycle Arrest and Inhibits Survival of Human Renal Cancer Cells by Negative Modulation of the PI3K/AKT Signaling Pathway.

    PubMed

    Zhang, Hao; Xu, Weili; Li, Baolin; Zhang, Kai; Wu, Yudong; Xu, Haidong; Wang, Junyong; Zhang, Jun; Fan, Rui; Wei, Jinxing

    2015-12-01

    Curcumin possesses anti-cancer effects. In the current study, we tested the effect of curcumin on cell proliferation, viability, apoptosis, cell cycle phases, and activation of the PI3K/Akt pathway in the renal cell carcinoma (RCC) cell line RCC-949. We observed that cell proliferation and viability were markedly inhibited by curcumin, while cell apoptosis was promoted. The latter effect was associated with increased expression of Bcl-2 and diminished expression of Bax (both: mRNA and protein). The cells treated with curcumin increasingly went into cell cycle arrest, which was likely mediated by diminished expression of cyclin B1, as seen in curcumin-treated cells. In addition, curcumin decreased activation of the PI3K/AKT signaling pathway. In conclusion, our results demonstrate that curcumin exerts anti-cancer effects by negative modulation of the PI3K/AKT signaling pathway and may represent a promising new drug to treat RCC. PMID:27259310

  3. Curcumin exerts inhibitory effects on undifferentiated nasopharyngeal carcinoma by inhibiting the expression of miR-125a-5p.

    PubMed

    Gao, Wei; Chan, Jimmy Yu-Wai; Wong, Thian-Sze

    2014-11-01

    Curcumin suppresses proliferation, migration, invasion, metastasis and angiogenesis and induces apoptosis by regulating multiple signalling pathways and miRNAs in a wide variety of human malignancies. miRNAs play crucial roles in various steps of carcinogenesis in nasopharyngeal carcinoma (NPC); thus, they could serve as critical therapeutic targets for NPC treatment. Curcumin could provide a novel strategy to block or induce specific miRNAs for miRNA-based gene therapies. Nevertheless, there are no reports to date on the miRNAs regulated by curcumin in NPC. In the present study, we have carried out an miRNA microarray to identify the miRNAs regulated by curcumin in NPC. Curcumin treatment down-regulated the expression of hsa-miR-125a-5p, hsa-miR-574-3p and hsa-miR-210 as determined by miRNA microarray analysis and qPCR (real-time quantitative reverse transcription-PCR). Forced expression of miR-125a-5p enhanced proliferation, migration and invasion of HONE1 cells. Primary NPC exhibited a significantly higher expression level of miR-125a-5p than healthy controls. miR-125a-5p inhibited the expression of tumour protein 53 (TP53), and curcumin treatment up-regulated the expression of TP53. Taken together, these results indicate that curcumin exerted inhibitory effects on NPC by inhibiting the expression of miR-125a-5p and, subsequently, enhancing the expression of TP53. Curcumin could provide a novel strategy to block miR-125a-5p for miRNA-based gene therapies in NPC. PMID:24896104

  4. Optimization and evaluation of a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles

    PubMed Central

    Lou, Jie; Hu, Wenjing; Tian, Rui; Zhang, Hua; Jia, Yuntao; Zhang, Jingqing; Zhang, Liangke

    2014-01-01

    This study aimed to optimize and evaluate a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles (Cur-BSA-NPs-Gel). Albumin nanoparticles were prepared via a desolvation method, and the gels were prepared via a cold method. The central composite design and response surface method was used to evaluate the effects of varying Pluronic® F127 and Pluronic® F68 concentrations on the sol–gel transition temperature, which is an indicator of optimum formulations. The optimized formulation was a free-flowing liquid below 30.9°C that transformed into a semi-solid gel above 34.2°C after dilution with simulated tear fluid. Results of the in vitro release and erosion behavior study indicated that Cur-BSA-NPs-Gel achieved superior sustained-release effects and that incorporation of albumin nanoparticles exerted minimal effects on the gel structure. In addition, in vivo ophthalmic experiments employing Cur-BSA-NPs-Gel were subsequently performed in rabbits. In vivo eye irritation results showed that Cur-BSA-NPs-Gel might be considered safe for ophthalmic drug delivery. The in vivo study also revealed that the formulation could significantly increase curcumin bioavailability in the aqueous humor. In conclusion, the optimized in situ gel formulation developed in this work has significant potential for ocular application. PMID:24904211

  5. Heat-solubilized curry spice curcumin inhibits antibody-antigen interaction in in vitro studies: a possible therapy to alleviate autoimmune disorders.

    PubMed

    Kurien, Biji T; D'Souza, Anil; Scofield, R Hal

    2010-08-01

    Chronic and complex autoimmune diseases, currently treated palliatively with immunosuppressives, require multi-targeted therapy for greater effectiveness. The naturally occurring polyphenol curcumin has emerged as a powerful "nutraceutical" that interacts with multiple targets to regress diseases safely and inexpensively. Up to 8 g/day of curcumin for 18 months was non-toxic to humans. However, curcumin's utility is limited by its aqueous insolubility. We have demonstrated a heat-mediated 12-fold increase in curcumin's aqueous solubility. Here, we show by SDS-PAGE and surface plasmon resonance that heat-solubilized curcumin binds to proteins. Based on this binding we hypothesized that heat-solubilized curcumin or turmeric would prevent autoantibody targeting of cognate autoantigens. Heat-solubilized curcumin/turmeric significantly decreased binding of autoantibodies from Sjögren's syndrome (up to 43/70%, respectively) and systemic lupus erythematosus (up to 52/70%, respectively) patients as well as an animal model of Sjögren's syndrome (up to 50/60%, respectively) to their cognate antigens. However, inhibition was not specific to autoimmunity. Heat-solubilized curcumin/turmeric also inhibited binding of commercial polyclonal anti-spectrin to spectrin (50/56%, respectively). Thus, we suggest that the multifaceted heat-solubilized curcumin can ameliorate autoimmune disorders. In addition, the non-toxic curcumin could serve as a new protein stain in SDS-PAGE even though it is less sensitive than the Coomassie system which involves toxic chemicals. PMID:20146265

  6. A modified spontaneous emulsification solvent diffusion method for the preparation of curcumin-loaded PLGA nanoparticles with enhanced in vitro anti-tumor activity

    NASA Astrophysics Data System (ADS)

    Chen, Cen; Yang, Wei; Wang, Dan-Tong; Chen, Chao-Long; Zhuang, Qing-Ye; Kong, Xiang-Dong

    2014-12-01

    To improve the anti-tumor activity of hydrophobic drug curcumin, we prepared curcumin-loaded PLGA nanoparticles (PLGA-Cur NPs) through a modified spontaneous emulsification solvent diffusion (modified-SESD) method. The influence of main preparation parameters was investigated, such as the volume ratio of binary organic solvents and the concentration of surfactant. Results indicated that the synthesized regular spherical PLGA NPs with the average diameter of 189.7 nm exhibited relatively higher yield (58.9%), drug loading (11.0% (w/w)) and encapsulation efficiency (33.5%), and also a controllable drug release profile. In order to evaluate the in vitro cytotoxicity of the prepared NPs, MTT assay was conducted, and results showed that the NPs could effectively inhibit HL60 and HepG2 cells with lower IC50 values compared with free curcumin. Furthermore, confocal microscopy together with flow cytometry analysis proved the enhanced apoptosis-inducing ability of PLGA-Cur NPs. Polymeric NP formulations are potential to be used for hydrophobic drug delivery systems in cancer therapy.

  7. pH-driven encapsulation of curcumin in self-assembled casein nanoparticles for enhanced dispersibility and bioactivity.

    PubMed

    Pan, Kang; Luo, Yangchao; Gan, Yundi; Baek, Seung J; Zhong, Qixin

    2014-09-21

    The poor water solubility and bioactivity of lipophilic phytochemicals can be potentially improved by delivery systems. In this study, a low-cost, low-energy, and organic solvent-free encapsulation technology was studied by utilizing the pH-dependent solubility properties of curcumin and self-assembly properties of sodium caseinate (NaCas). Curcumin was deprotonated and dissolved, while NaCas was dissociated at pH 12 and 21 °C for 30 min. The subsequent neutralization enabled the encapsulation of curcumin in self-assembled casein nanoparticles. The degradation of curcumin under encapsulation conditions was negligible based on visible light and nuclear magnetic resonance spectroscopy. The dissociation of NaCas at pH 12 and reassociation after neutralization were confirmed using dynamic light scattering and analytical ultracentrifugation. The curcumin encapsulated in casein nanoparticles showed significantly improved anti-proliferation activity against human colorectal and pancreatic cancer cells. The studied encapsulation method is promising to utilize lipophilic compounds in food or pharmaceutical industries. PMID:25082426

  8. Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization.

    PubMed

    Hazzah, Heba A; Farid, Ragwa M; Nasra, Maha M A; El-Massik, Magda A; Abdallah, Ossama Y

    2015-08-15

    This study aimed to prepare and evaluate mucoadhesive sponges as dosage forms for delivering solid lipid nanoparticles. For this purpose curcumin (Cur) was formulated as solid nanoparticles (SLN) using Gelucire 50/13, and polaxomer 407. The prepared CurSLN dispersion was thickened with different mucoadhesive polymers. Different concentrations of glycerol, and mannitol of range (0.25-20%), and (0-1%), respectively were also examined. The formed gel was poured into oblong molds and freeze dried to form mucoadhesive sponge to be applied to the buccal mucosa. The prepared sponges were evaluated for their, in-vivo residence time, in-vitro and in-vivo drug release, and hydration capacity. Surface morphology for the different sponges were examined using SEM. TEM was also carried out for sponge fragments previously dispersed into water. Infrared spectroscopy was conducted to investigate interaction between used ingredients. The results showed that the CurSLN loaded HPMC, and Polycarbophil sponges showed 4, and 15 h in-vivo residence time, respectively, providing a considerable amount of curcumin into saliva. The incorporation of glycerol and mannitol at concentration of 1% provided elegant and flexible sponges. The SEM showed that the deposition of CurSLN differed according to the type of polymer used. TEM confirmed the integrity of liberated CurSLN from sponges. IR spectra showed an interaction between HPMC and poloxamer 407, which affected its behavior as a gelling agent. The obtained results provide an efficient approach for delivering solid lipid nanoparticles in a solid dosage form keeping the nanoparticle characters and integrity. PMID:26189427

  9. Molecular docking studies on inhibition of Stat3 dimerization by curcumin natural derivatives and its conjugates with amino acids

    PubMed Central

    Kumar, Anil; Bora, Utpal

    2012-01-01

    Stat3 is a mammalian transcription factor which regulates various genes involved in cell growth, proliferation, cell survival and other biological processes. Its constitutive activation promotes dysregulated growth, survival and immune responses which contribute to tumor progression and carcinogenesis. Inhibition of Stat3 dimerization which prevents its binding to DNA is a rational strategy that could be translated to potential therapeutic applications. The present computational study provides insights into the inhibition of Stat3 dimerization by curcumin natural derivatives and its conjugates with amino acids. The involvement of residues like LYS-591, ARG-609, SER-611, GLU-612, SER-613, SER-636 and VAL-637 seems to play an important role in binding of curcumin natural derivatives and its amino acids conjugates with Src Homology (SH2) domain of Stat3 monomer. Demethoxycurcumin followed by hexahydrocurcuminol were predicted to be the most potent inhibitors amongst all the curcumin natural derivatives and known inhibitors (FLLL32, Sta21 and Stattic). Curcumin-proline conjugate (1,7-Bis(4-O-L-prolinoyl-3- methoxyphenyl)-1,4,6-heptatriene-5-ol-3-one) was predicted to be the most potent inhibitor of Stat3 dimerization amongst the curcumin-amino acid conjugates and known peptide based inhibitor (Phpr-pTYR-LEU-cis-3,4-methanoPRO-GLN-NHBn). PMID:23275693

  10. Molecular docking studies on inhibition of Stat3 dimerization by curcumin natural derivatives and its conjugates with amino acids.

    PubMed

    Kumar, Anil; Bora, Utpal

    2012-01-01

    Stat3 is a mammalian transcription factor which regulates various genes involved in cell growth, proliferation, cell survival and other biological processes. Its constitutive activation promotes dysregulated growth, survival and immune responses which contribute to tumor progression and carcinogenesis. Inhibition of Stat3 dimerization which prevents its binding to DNA is a rational strategy that could be translated to potential therapeutic applications. The present computational study provides insights into the inhibition of Stat3 dimerization by curcumin natural derivatives and its conjugates with amino acids. The involvement of residues like LYS-591, ARG-609, SER-611, GLU-612, SER-613, SER-636 and VAL-637 seems to play an important role in binding of curcumin natural derivatives and its amino acids conjugates with Src Homology (SH2) domain of Stat3 monomer. Demethoxycurcumin followed by hexahydrocurcuminol were predicted to be the most potent inhibitors amongst all the curcumin natural derivatives and known inhibitors (FLLL32, Sta21 and Stattic). Curcumin-proline conjugate (1,7-Bis(4-O-L-prolinoyl-3- methoxyphenyl)-1,4,6-heptatriene-5-ol-3-one) was predicted to be the most potent inhibitor of Stat3 dimerization amongst the curcumin-amino acid conjugates and known peptide based inhibitor (Phpr-pTYR-LEU-cis-3,4-methanoPRO-GLN-NHBn). PMID:23275693

  11. Activation of PPARgamma is required for curcumin to induce apoptosis and to inhibit the expression of extracellular matrix genes in hepatic stellate cells in vitro.

    PubMed

    Zheng, Shizhong; Chen, Anping

    2004-11-15

    During liver fibrogenesis, quiescent HSC (hepatic stellate cells) become active, a transformation that is associated with enhanced cell proliferation and overproduction of ECM (extracellular matrix). Inhibition of cell proliferation and induction of apoptosis are potential strategies to block the activation of HSC for the prevention and treatment of liver fibrosis. Levels of PPARgamma (peroxisome proliferator-activated receptor gamma) are dramatically diminished in parallel with HSC activation. Stimulation of PPARgamma by its agonists inhibits HSC activation in vitro and in vivo. We demonstrated recently that curcumin, the yellow pigment in curry, inhibited HSC activation in vitro, reducing cell proliferation, inducing apoptosis and inhibiting ECM gene expression. Further studies indicated that curcumin induced the gene expression of PPARgamma and stimulated its activity in activated HSC in vitro, which was required for curcumin to inhibit HSC proliferation. The aims of the present study were to evaluate the roles of PPARgamma activation in the induction of apoptosis and suppression of ECM gene expression by curcumin in activated HSC, and to elucidate the underlying mechanisms. Our results demonstrated that blocking PPARgamma activation abrogated the effects of curcumin on the induction of apoptosis and inhibition of the expression of ECM genes in activated HSC in vitro. Further experiments demonstrated that curcumin suppressed the gene expression of TGF-beta (transforming growth factor-beta) receptors and interrupted the TGF-beta signalling pathway in activated HSC, which was mediated by PPARgamma activation. Taken together, our results demonstrate that curcumin stimulated PPARgamma activity in activated HSC in vitro, which was required for curcumin to reduce cell proliferation, induce apoptosis and suppress ECM gene expression. These results provide novel insight into the mechanisms responsible for the inhibition of HSC activation by curcumin. The characteristics

  12. Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-β/Smad2/3 signaling pathway.

    PubMed

    Zhang, Li; Cheng, Xian; Gao, Yanyan; Zhang, Chiyu; Bao, Jiandong; Guan, Haixia; Yu, Huixin; Lu, Rongrong; Xu, Qiang; Sun, Yang

    2016-02-15

    Thyroid cancers usually possess a good prognosis while the risks of recurrence and metastasis turn out to be a disturbing issue. Curcumin [bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione] is a natural polyphenolic compound mainly found in turmeric (Curcuma longa). Our previous studies have demonstrated that curcumin showed proliferation-inhibitory and apoptosis-inducing effects on K1 papillary thyroid cancer cells. However, the mechanism underlying the inhibition effects of curcumin on thyroid cancer cells remains unclear. Herein, we demonstrated that curcumin remarkably increased the expression of the epithelial marker E-cadherin and repressed the expression of the mesenchymal marker vimentin in human papillary thyroid carcinoma BCPAP cells. Curcumin also suppressed multiple metastatic steps of BCPAP cells, including cell attachment, spreading as well as migration. In addition, the transcription, secretion and activation of matrix metalloproteinases (MMPs) induced by transforming growth factor-β1 (TGF-β1) in BCPAP cells were mitigated upon curcumin treatment. Further evidence showed that curcumin decreased TGF-β1-mediated phosphorylation of Smad2 and Smad3. These results revealed that curcumin inhibited the TGF-β1-induced epithelial-mesenchymal transition (EMT) via down-regulation of Smad2/3 signaling pathways. Our findings provide new evidence that the anti-metastatic and anti-EMT activities of curcumin may contribute to the development of chemo-preventive agents for thyroid cancer treatment. PMID:26826337

  13. Preparation and characterization of curcumin-piperine dual drug loaded nanoparticles

    PubMed Central

    Moorthi, C; Krishnan, Kiran; Manavalan, R; Kathiresan, K

    2012-01-01

    Objective To prepare curcumin-piperine (Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation of Cu-Pi nanoparticles to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer. Methods Cu-Pi nanoparticles were prepared by thin film hydration method, solid dispersion method, emulsion polymerization method and Fessi method. Optimization was carried out to study the effect of various manufacturing parameter on the Cu-Pi nanoparticles. Results Out of four methods, Fessi method produced a minimum average particle size of 85.43 nm with a polydispersity index of 0.183 and zeta potential of 29.7 mV. Change of organic solvent (acetone or ethanol) did not have any significant effect on Cu-Pi nanoparticles. However, increase in sonication time, stirring speed, viscosity, use of 1:10:10 ratio of drug/polymer/surfactant, and use of anionic surfactant or combination of anionic surfactant with cationic polymer or combination of non-ionic surfactant with cationic polymer had a significant effect on Cu-Pi nanoparticles. Conclusions Cu-Pi nanoparticles coated with PEG containing copolymer produced by Fessi method had a minimum average particle size, excellent polydispersity index and optimal zeta potential which fall within the acceptable limits of the study. This dual nanoparticulate drug delivery system appears to be promising to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer. PMID:23569859

  14. Curcumin attenuates brain edema in mice with intracerebral hemorrhage through inhibition of AQP4 and AQP9 expression

    PubMed Central

    Wang, Bao-feng; Cui, Zhen-wen; Zhong, Zhi-hong; Sun, Yu-hao; Sun, Qing-fang; Yang, Guo-yuan; Bian, Liu-guan

    2015-01-01

    Aim: Aquaporins (AQPs) are the water-channels that play important roles in brain water homeostasis and in cerebral edema induced by brain injury. In this study we investigated the relationship between AQPs and a neuroprotective agent curcumin that was effective in the treatment of brain edema in mice with intracerebral hemorrhage (ICH). Methods: ICH was induced in mice by autologous blood infusion. The mice immediately received curcumin (75, 150, 300 mg/kg, ip). The Rotarod test scores, brain water content and brain expression of AQPs were measured post ICH. Cultured primary mouse astrocytes were used for in vitro experiments. The expression of AQP1, AQP4 and AQP9 and NF-κB p65 were detected using Western blotting or immunochemistry staining. Results: Curcumin administration dose-dependently reduced the cerebral edema at d 3 post ICH, and significantly attenuated the neurological deficits at d 5 post ICH. Furthermore, curcumin dose-dependently decreased the gene and protein expression of AQP4 and AQP9, but not AQP1 post ICH. Treatment of the cultured astrocytes with Fe2+ (10–100 μmol/L) dose-dependently increased the expression and nuclear translocation of NF-κB p65 and the expression of AQP4 and AQP9, which were partly blocked by co-treatment with curcumin (20 μmol/L) or the NF-κB inhibitor PDTC (10 μmol/L). Conclusion: Curcumin effectively attenuates brain edema in mice with ICH through inhibition of the NF-κB pathway and subsequently the expression of AQP4 and AQP9. Curcumin may serve as a potential therapeutic agent for ICH. PMID:26119880

  15. Curcumin Inhibits Glyoxalase 1—A Possible Link to Its Anti-Inflammatory and Anti-Tumor Activity

    PubMed Central

    Santel, Thore; Pflug, Gabi; Hemdan, Nasr Y. A.; Schäfer, Angelika; Hollenbach, Marcus; Buchold, Martin; Hintersdorf, Anja; Lindner, Inge; Otto, Andreas; Bigl, Marina; Oerlecke, Ilka; Hutschenreuter, Antje; Sack, Ulrich; Huse, Klaus; Groth, Marco; Birkemeyer, Claudia; Schellenberger, Wolfgang; Gebhardt, Rolf; Platzer, Mathias; Weiss, Thomas; Vijayalakshmi, Mookambeswaran A.; Krüger, Monika; Birkenmeier, Gerd

    2008-01-01

    Background Glyoxalases (Glo1 and Glo2) are involved in the glycolytic pathway by detoxifying the reactive methylglyoxal (MGO) into D-lactate in a two-step reaction using glutathione (GSH) as cofactor. Inhibitors of glyoxalases are considered as anti-inflammatory and anti-carcinogenic agents. The recent finding that various polyphenols modulate Glo1 activity has prompted us to assess curcumin's potency as an Glo1 inhibitor. Methodology/Principal Findings Cultures of whole blood cells and tumor cell lines (PC-3, JIM-1, MDA-MD 231 and 1321N1) were set up to investigate the effect of selected polyphenols, including curcumin, on the LPS-induced cytokine production (cytometric bead-based array), cell proliferation (WST-1 assay), cytosolic Glo1 and Glo2 enzymatic activity, apoptosis/necrosis (annexin V-FITC/propidium iodide staining; flow cytometric analysis) as well as GSH and ATP content. Results of enzyme kinetics revealed that curcumin, compared to the polyphenols quercetin, myricetin, kaempferol, luteolin and rutin, elicited a stronger competitive inhibitory effect on Glo1 (Ki = 5.1±1.4 µM). Applying a whole blood assay, IC50 values of pro-inflammatory cytokine release (TNF-α, IL-6, IL-8, IL-1β) were found to be positively correlated with the Ki-values of the aforementioned polyphenols. Moreover, whereas curcumin was found to hamper the growth of breast cancer (JIMT-1, MDA-MB-231), prostate cancer PC-3 and brain astrocytoma 1321N1 cells, no effect on growth or vitality of human primary hepatocytes was elucidated. Curcumin decreased D-lactate release by tumor cells, another clue for inhibition of intracellular Glo1. Conclusions/Significance The results described herein provide new insights into curcumin's biological activities as they indicate that inhibition of Glo1 by curcumin may result in non-tolerable levels of MGO and GSH, which, in turn, modulate various metabolic cellular pathways including depletion of cellular ATP and GSH content. This may account

  16. In situ synthesis and surface functionalization of gold nanoparticles with curcumin and their antioxidant properties: an experimental and density functional theory investigation

    NASA Astrophysics Data System (ADS)

    Singh, Dheeraj K.; Jagannathan, Ramya; Khandelwal, Puneet; Abraham, Priya Mary; Poddar, Pankaj

    2013-02-01

    Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is an active component of turmeric; it is responsible for its characteristic yellow color and therapeutic potential, but its poor bioavailability remains a major challenge. In order to improve the bioavailability of curcumin, various approaches have been used. One of the possible approaches to increase the bioavailability of curcumin is its conjugation on the surface of metal nanoparticles. Therefore, in the present study, we report the binding of curcumin on the surface of gold nanoparticles (AuNPs). The AuNPs were synthesized by the direct reduction of HAuCl4 using curcumin in the aqueous phase, without the use of any other reducing agents. We found that curcumin acts both as a reducing and capping agent, stabilizing the gold sol for many months. Moreover, these curcumin-capped AuNPs also show good antioxidant activity which was confirmed by the DPPH (2,2-diphenyl-l-picrylhydrazyl) radical test. Thus, the surface functionalization of AuNPs with curcumin may pave a new way of using the curcuminoids towards possible drug delivery and therapeutics. Apart from the experimental study, a detailed quantum chemical calculation using density functional theory (DFT) has been performed, in order to investigate the formation of a complex of curcumin with Au3+ ions in different possible conformational isomeric forms. Our theoretical calculations indicate the evidence of electron transfer from curcumin into the Au center and essentially indicate that as a consequence of complexation, Au3+ ions are reduced to Au0. Our theoretical results also propose that it is the breakage of intramolecular H-bonding that probably leads to the increased availability of curcumin in the presence of gold ions and water molecules.Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is an active component of turmeric; it is responsible for its characteristic yellow color and therapeutic

  17. Low-dose curcumin leads to the inhibition of tumor growth via enhancing CTL-mediated antitumor immunity.

    PubMed

    Luo, Feifei; Song, Xiao; Zhang, Yi; Chu, Yiwei

    2011-09-01

    Curcumin, a yellow pigment extracted from turmeric, is widely used to inhibit tumor progression. Since it can either promote or suppress the immune system, how curcumin affects the immune system in tumor-bearing bodies is not yet clear. Our study found that tumor-bearing mice treated consecutively once a day with low-dose curcumin for ten days led to a retarded tumor growth and a longer survival, which might be contributed to T cell-mediated adaptive immune response. The in vitro study also showed that a high-dose curcumin decreases T cells whereas a low-dose increases T cells derived from 3LL tumor-bearing mice, especially CD8+ T cells. Accordingly, these increased CD8+ T cells exhibited the enhancement of IFN-γ secretion, proliferation and cytotoxicity specifically against 3LL tumor cells, which may result in the success of antitumor immunity. Our research demonstrated a beneficial effect of curcumin on CD8+ T cells derived from tumor-bearing mice, which can provide a potential application in anti-tumor therapy. PMID:21497674

  18. Targeted Nanogel Conjugate for Improved Stability and Cellular Permeability of Curcumin: Synthesis, Pharmacokinetics, and Tumor Growth Inhibition

    PubMed Central

    2015-01-01

    Curcumin (CUR) is a unique natural compound with promising anticancer and anti-inflammatory activities. However, the therapeutic efficacy of curcumin was challenged in clinical trials, mostly due to its low bioavailability, rapid metabolism, and elimination. We designed a nanodrug form of curcumin, which makes it stable and substantially enhances cellular permeability and anticancer activity at standard oral administration. Curcumin was conjugated as an ester to cholesteryl-hyaluronic acid (CHA) nanogel that is capable of targeted delivery to CD44-expressing drug-resistant cancer cells. CHA-CUR nanogels demonstrated excellent solubility and sustained drug release in physiological conditions. It induced apoptosis in cancer cells, suppressing the expression of NF-κB, TNF-α, and COX-2 cellular targets similar to free curcumin. Pharmacokinetic/pharmacodynamic (PK/PD) studies also revealed improved circulation parameters of CHA-CUR at oral, i.p. and i.v. administration routes. CHA-CUR showed targeted tumor accumulation and effective tumor growth inhibition in human pancreatic adenocarcinoma MiaPaCa-2 and aggressive orthotropic murine mammary carcinoma 4T1 animal models. CHA-CUR treatment was well-tolerated and resulted in up to 13-fold tumor suppression, making this nanodrug a potential candidate for cancer prevention and therapeutic treatment. PMID:25072100

  19. Curcumin Enhances Dasatinib Induced Inhibition of Growth and Transformation of Colon Cancer Cells

    PubMed Central

    Nautiyal, Jyoti; Banerjee, Sanjeev; Kanwar, Shailender S; Yu, Yingjie; Patel, Bhaumik B; Sarkar, Fazlul H; Majumdar, Adhip P. N.

    2010-01-01

    Colorectal cancer is the third most common form of malignancy, behind prostate and lung cancers. Despite recent advances in medicine, mortality from colorectal cancer remains high, highlighting the need for improved therapies. Numerous studies have demonstrated increased activation of EGFR and its family members (EGFRs), IGF-1R as well as c-Src in colorectal cancer. The current study was undertaken to examine the effectiveness of combination therapy of dasatinib (BMS-354825; Bristol-Myers Squibb), a highly specific inhibitor of Src family kinases (SFK) and a non-toxic dietary agent; curcumin (diferuloylmethane), in colorectal cancer in in vitro and in vivo experimental models. For the latter we utilized C57BL/6J-ApcMin+/− mice. Initial in vitro studies revealed synergistic interactions between the two agents. Additionally, we have observed that combination treatment causes a much greater inhibition of the following metastatic processes than either agent alone: (a) colony formation (b) invasion through extracellular matrix (c) tubule formation by endothelial cells. Dasatinib affects the cell adhesion phenotype of colon cancer HCT-116 cells whereas the combination therapy enhances this effect to a greater extent. Preclinical investigation revealed that the combination therapy to be highly effective causing an over 95% regression of intestinal adenomas in ApcMin+/− mice, which could be attributed to decreased proliferation and increased apoptosis. In conclusion, our data suggest that combination treatment of dasatinib and curcumin could be a potential therapeutic strategy for colorectal cancer. PMID:20473900

  20. Concanavaline A conjugated bacterial polyester-based PHBHHx nanoparticles loaded with curcumin for breast cancer therapy.

    PubMed

    Kilicay, Ebru; Karahaliloglu, Zeynep; Hazer, Baki; Tekin, Ishak Özel; Denkbas, Emir Baki

    2016-05-01

    The aim of this study was to evaluate therapeutic potential of curcumin-loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin-loaded NPs (ConA-CUR-NPs) for breast cancer treatment. The size and zeta potential of prepared NPs were about 228 ± 5 nm and -23.3 mV, respectively. The entrapment efficiencies of polymer/drug weight ratios, 1.25CUR-NPs, 2.5CUR-NPs, 5CUR-NPs, ConA-1.25CUR-NPs, ConA-2.5CUR-NPs and ConA-5CUR-NPs were found to be ≈68, 55, 45, 70, 60 and 51%, respectively. Optimized NPs formulations in the freeze-dried form were assessed with their short-term stability for 30 days of storage at 4 °C and 25 °C. Anticancer activity of ConA-CUR-NPs was proved by MTT assay and reconfirmed by double staining and flow cytometry results. The anticancer activity of ConA-CUR-NPs was measured in human breast cancer cells (MDA-MB 231) in vitro, and the results revealed that the ConA-CUR-NPs had better tumor cells decline activity. PMID:27049468

  1. Gelsolin Amyloidogenesis Is Effectively Modulated by Curcumin and Emetine Conjugated PLGA Nanoparticles

    PubMed Central

    Goel, Surbhi; Kundu, Bishwajit; Mishra, Prashant; Fnu, Ashish

    2015-01-01

    Small molecule based therapeutic intervention of amyloids has been limited by their low solubility and poor pharmacokinetic characteristics. We report here, the use of water soluble poly lactic-co-glycolic acid (PLGA)-encapsulated curcumin and emetine nanoparticles (Cm-NPs and Em-NPs, respectively), as potential modulators of gelsolin amyloidogenesis. Using the amyloid-specific dye Thioflavin T (ThT) as an indicator along with electron microscopic imaging we show that the presence of Cm-NPs augmented amyloid formation in gelsolin by skipping the pre-fibrillar assemblies, while Em-NPs induced non-fibrillar aggregates. These two types of aggregates differed in their morphologies, surface hydrophobicity and secondary structural signatures, confirming that they followed distinct pathways. In spite of differences, both these aggregates displayed reduced toxicity against SH-SY5Y human neuroblastoma cells as compared to control gelsolin amyloids. We conclude that the cytotoxicity of gelsolin amyloids can be reduced by either stalling or accelerating its fibrillation process. In addition, Cm-NPs increased the fibrillar bulk while Em-NPs defibrillated the pre-formed gelsolin amyloids. Moreover, amyloid modulation happened at a much lower concentration and at a faster rate by the PLGA encapsulated compounds as compared to their free forms. Thus, besides improving pharmacokinetic and biocompatible properties of curcumin and emetine, PLGA conjugation elevates the therapeutic potential of both small molecules against amyloid fibrillation and toxicity. PMID:25996685

  2. Inhibition of LPS-induced production of inflammatory factors in the macrophages by mono-carbonyl analogues of curcumin

    PubMed Central

    Liang, Guang; Zhou, Huiping; Wang, Yi; Gurley, Emily C; Feng, Biao; Chen, Li; Xiao, Jian; Yang, Shulin; Li, Xiaokun

    2009-01-01

    Curcumin (diferuloylmethane) is an orange–yellow compound from turmeric (Curcuma longa), a spice found in curry powder. Traditionally known for its anti-inflammatory effects, curcumin has established itself in the last two decades to be a potent immunomodulatory agent that can regulate the activation of a variety of immunocytes and the expression of inflammatory factors. Considering that the β-diketone moiety of curcumin may result in its instability and poor metabolic property, we previously designed a series of mono-carbonyl analogues of curcumin with enhanced stability by deleting this moiety. These compounds demonstrate improved pharmacokinetic profiles both in vitro and in vivo. In this study, we reported a total of 44 mono-carbonyl analogues, which have been evaluated for the inhibitory activities against LPS-induced TNF-α and IL-6 release in the macrophages. Based on the screening results of these analogues, five active compounds A01, A03, A13, B18 and C22 were investigated to inhibit TNF-α and IL-6 release in a dose-dependent manner, three of which further demonstrated inhibitory effects on LPS-induced TNF-α, IL-1β, IL-6, MCP-1, COX-2, PGES, iNOS and p65 NF-κB mRNA production. The results indicated that these mono-carbonyl analogues may possess anti-inflammatory activities similar to curcumin despite the absence of the β-diketone. These mono-carbonyl analogues may be a favourable alternative for the development of curcumin-based anti-inflammatory drugs both pharmacokinetically and pharmacologically. We further examined the biological properties of A13, the only hydrosoluble analogue when combined with hydrochloric acid. The results showed a dose-dependent inhibition of LPS-induced cytokine production. These data further indicated that compound A13 may be explored as a promising anti-inflammatory molecule. PMID:19243473

  3. In situ synthesis and surface functionalization of gold nanoparticles with curcumin and their antioxidant properties: an experimental and density functional theory investigation.

    PubMed

    Singh, Dheeraj K; Jagannathan, Ramya; Khandelwal, Puneet; Abraham, Priya Mary; Poddar, Pankaj

    2013-03-01

    Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is an active component of turmeric; it is responsible for its characteristic yellow color and therapeutic potential, but its poor bioavailability remains a major challenge. In order to improve the bioavailability of curcumin, various approaches have been used. One of the possible approaches to increase the bioavailability of curcumin is its conjugation on the surface of metal nanoparticles. Therefore, in the present study, we report the binding of curcumin on the surface of gold nanoparticles (AuNPs). The AuNPs were synthesized by the direct reduction of HAuCl(4) using curcumin in the aqueous phase, without the use of any other reducing agents. We found that curcumin acts both as a reducing and capping agent, stabilizing the gold sol for many months. Moreover, these curcumin-capped AuNPs also show good antioxidant activity which was confirmed by the DPPH (2,2-diphenyl-l-picrylhydrazyl) radical test. Thus, the surface functionalization of AuNPs with curcumin may pave a new way of using the curcuminoids towards possible drug delivery and therapeutics. Apart from the experimental study, a detailed quantum chemical calculation using density functional theory (DFT) has been performed, in order to investigate the formation of a complex of curcumin with Au(3+) ions in different possible conformational isomeric forms. Our theoretical calculations indicate the evidence of electron transfer from curcumin into the Au center and essentially indicate that as a consequence of complexation, Au(3+) ions are reduced to Au(0). Our theoretical results also propose that it is the breakage of intramolecular H-bonding that probably leads to the increased availability of curcumin in the presence of gold ions and water molecules. PMID:23348618

  4. Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line.

    PubMed

    Chopra, Deepti; Ray, Lipika; Dwivedi, Ashish; Tiwari, Shashi Kant; Singh, Jyoti; Singh, Krishna P; Kushwaha, Hari Narayan; Jahan, Sadaf; Pandey, Ankita; Gupta, Shailendra K; Chaturvedi, Rajnish Kumar; Pant, Aditya Bhushan; Ray, Ratan Singh; Gupta, Kailash Chand

    2016-04-01

    Curcumin (Cur) has been demonstrated to have wide pharmacological window including anti-oxidant and anti-inflammatory properties. However, phototoxicity under sunlight exposure and poor biological availability limits its applicability. We have synthesized biodegradable and non-toxic polymer-poly (lactic-co-glycolic) acid (PLGA) encapsulated formulation of curcumin (PLGA-Cur-NPs) of 150 nm size range. Photochemically free curcumin generates ROS, lipid peroxidation and induces significant UVA and UVB mediated impaired mitochondrial functions leading to apoptosis/necrosis and cell injury in two different origin cell lines viz., mouse fibroblasts-NIH-3T3 and human keratinocytes-HaCaT as compared to PLGA-Cur-NPs. Molecular docking studies suggested that intact curcumin from nanoparticles, bind with BAX in BIM SAHB site and attenuate it to undergo apoptosis while upregulating anti-apoptotic genes like BCL2. Real time studies and western blot analysis with specific phosphorylation inhibitor of ERK1 and AKT1/2/3 confirm the involvement of ERK/AKT signaling molecules to trigger the survival cascade in case of PLGA-Cur-NPs. Our finding demonstrates that low level sustained release of curcumin from PLGA-Cur-NPs could be a promising way to protect the adverse biological interactions of photo-degradation products of curcumin upon the exposure of UVA and UVB. Hence, the applicability of PLGA-Cur-NPs could be suggested as prolonged radical scavenging ingredient in curcumin containing products. PMID:26803409

  5. Sensitizing nanoparticle based platinum(IV) drugs by curcumin for better chemotherapy.

    PubMed

    Kang, Xiang; Zhao, Chen; Yan, Lesan; Qi, Ruogu; Jing, Xiabin; Wang, Zehua

    2016-09-01

    A polymer-cisplatin(IV) conjugate was prepared by attaching Pt(IV)-COOH to a biodegradable amphiphilic block copolymer containing pendant OH groups. The conjugate can assemble into micelles (M(Pt)) with a mean diameter of ca. 169nm. Further, curcumin (CM) was used to sensitize platinum drug based nanoparticles to overcome cisplatin resistance and enhance antitumor efficacy. In vitro studies showed that M(Pt)/CM combinations had great synergistic effect both on cisplatin sensitive and cisplatin resistant cell lines (A2780 and A2780DDP). In vivo studies showed that M(Pt)/CM had a much lower systemic toxicity and an enhanced antitumor efficacy compared to cisplatin alone or the corresponding cisplatin/CM combinations. Therefore, polymer-cisplatin(IV) conjugate with small molecules that serve as a non-cytotoxic or minimally cytotoxic sensitizer or enhancer provide a promising strategy, which may have potential clinical implications in the near future. PMID:27311131

  6. Preparation and cytotoxicity of N-modified chitosan nanoparticles applied in curcumin delivery.

    PubMed

    Facchi, Suelen P; Scariot, Débora B; Bueno, Pedro V A; Souza, Paulo R; Figueiredo, Luana C; Follmann, Heveline D M; Nunes, Cátia S; Monteiro, Johny P; Bonafé, Elton G; Nakamura, Celso V; Muniz, Edvani C; Martins, Alessandro F

    2016-06-01

    Nanoparticles (NPs) based on N,N-dimethyl chitosan (DMC) and N,N,N-trimethyl chitosan (TMC), physical crosslinked with sodium tripolyphosphate (TPP) were successful obtained, using water/benzyl alcohol emulsion system. NPs morphologies were evaluated by Scanning Electron Microscopy and Transmission Electron Microscopy. NPs were characterized by Infrared Spectroscopy (FTIR), Thermogravimetric Analysis, Zeta Potential, Differential Scanning Calorimetry and Wide-angle X-ray Scattering. Curcumin (CUR) was loaded onto NPs and controlled release studies were evaluated in simulated intestinal fluid and in simulated gastric fluid. Cytotoxicity assays showed only loaded TMC/TPP particles containing CUR were slightly cytotoxic on human cervical tumor cells (SiHa cells), concerning unloaded TMC/TPP particles. Conversely, loaded NPs (TMC/TPP/CUR and DMC/TPP/CUR), especially TMC/TPP/CUR sample presented greater biocompatibility toward healthy VERO cells than unloaded NPs (TMC/TPP and DMC/TPP). PMID:26930578

  7. Curcumin loaded PLGA-poloxamer blend nanoparticles induce cell cycle arrest in mesothelioma cells.

    PubMed

    Mayol, Laura; Serri, Carla; Menale, Ciro; Crispi, Stefania; Piccolo, Maria Teresa; Mita, Luigi; Giarra, Simona; Forte, Maurizio; Saija, Antonina; Biondi, Marco; Mita, Damiano Gustavo

    2015-06-01

    The pharmacological potential of curcumin (CURC) is severely restricted because of its low water solubility/absorption, short half-life and poor bioavailability. To overcome these issues, CURC-loaded nanoparticles (NPs) were produced by a double emulsion technique. In particular, NPs were made up of an amphiphilic blend of poloxamers and PLGA to confer stealth properties to the NPs to take advantage of the enhanced permeability and retention (EPR) effect. Different surface properties of NPs made up of bare PLGA and PLGA/poloxamer blend were confirmed by the different interactions of these NPs with serum proteins and also by their ability to be internalized by mesothelioma cell line. The uptake of PLGA/poloxamer NPs induces a persistent block in G0/G1 phase of the cell cycle up to 72 h, thus overcoming the drug tolerance phenomenon, normally evidenced with free CURC. PMID:25794477

  8. Mechanism of curcumin-induced trypsin inhibition: Computational and experimental studies

    NASA Astrophysics Data System (ADS)

    Wang, Yan-Qing; Zhang, Hong-Mei; Kang, Yi-Jun; Gu, Yun-Lan; Cao, Jian

    2016-03-01

    In the present study, the experimental and theoretical methods were used to analyze the binding interaction of food dye, curcumin with trypsin. The results of fluorescence spectroscopic measurements indicated that curcumin binding resulted in the obviously intrinsic fluorescence quenching with the increase concentration of curcumin. This binding interaction is a spontaneous process with the estimated enthalpy and entropy changes being -15.70 kJ mol-1 and 40.25 J mol-1 K-1, respectively. Hydrogen bonds and hydrophobic forces played an important role in the complex formation between curcumin and trypsin. Moreover, curcumin could enter into the primary substrate-binding pocket and makes the activity of trypsin decrease remarkably with the increasing concentration of curcumin.

  9. Relief of Oxidative Stress Using Curcumin and Glutathione Functionalized ZnO Nanoparticles in HEK-293 Cell Line.

    PubMed

    Kumar, Amit; Zafaryab, Md; Umar, Ahmad; Rizvi, M M A; Fouad, H; Ansari, Z A; Ansari, S G

    2015-11-01

    To elucidate the effect of zinc oxide nanoparticles (ZnO-NPs) with different surface modifications in relieving the oxidative stress in cultured human embryonic kidney cells (HEK-293) following investigation was performed. Oxidative stress was artificially induced by hydrogen peroxide in HEK-293 cell culture and its management was studied. Alkyl amines modified ZnO-NPs with curcumin and reduced glutathione (GSH) functionalization was used in managing oxidative stress and had shown promising results. ZnO-NPs used in this study were synthesized via non-aqueous sol-gel method and FESEM characterisation showed them of spherical shape of about 20-50 nm size with amine, curcumin and GSH functionalization. UV-visible and FTIR spectroscopic characterizations confirmed functionalization of ZnO-NPs. Decrease in oxidative stress was found with the dose-dependent culture of HEK-293 cells with these functionalized ZnO-NPs. Cell viability and morphology, as observed using AFM and inverted microscope, was retained with the prescribed dosages of the functionalized nanoparticles while at higher dosages they caused cytotoxicity and death. Diethylamine (DEA) modified ZnO-NPs and their functionalization with GSH and curcumin were found more effective in managing oxidative stress in cells. Present study could help in designing economical and bio-compatible functionalized non-toxic nanoparticles designed for managing oxidative stress leading to possible therapeutical and medicinal uses. PMID:26554152

  10. Curcumin inhibits cell proliferation and promotes apoptosis in human osteoclastoma cell through MMP-9, NF-κB and JNK signaling pathways.

    PubMed

    Cao, Fujiang; Liu, Tao; Xu, Yunqiang; Xu, Dongdong; Feng, Shiqing

    2015-01-01

    Curcumin is a polyphenol compound extracted from ginger plant, turmeric, commonly used in a variety of food coloring and flavoring additives. Curcumin has many effects such as anti-inflammatory, anti-tumor, antioxidant and anti-microbial effects. However, the mechanism underlying the anti-cancer effect of curcumin on human osteoclastoma (Giant cell tumor, GCT) cells remains unclear. The objectives of this study were to determine the efficacy of curcumin on proliferation and apoptosis of GCT cells and its related mechanisms. In our study, cell viability, cellular apoptosis and caspase-3 activity of GCT cells were analyzed using 3.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry (FCM) assay and commercial kits, respectively. Next, MMP-9 gene expression quantity, NF-κB activity and JNK protein expression of GCT cells were tested with real-time polymerase chain reaction (RT-PCR), commercial kits and western blotting assay, respectively. Firstly, MMP-9, NF-κB and JNK inhibitors were added into GCT cells and which was researched the mechanism of curcumin on human GCT cells. In this study, the efficacy of curcumin reduced cell viability, induced cellular apoptosis and increased caspase-3 activity of GCT cells. Furthermore, curcumin inhibited the MMP-9 gene expression quantity and NF-κB activity, and activated JNK protein expression in GCT cells. Meanwhile, down-regulation of MMP-9 gene expression quantity and NF-κB activity could promote the anti-cancer effect of curcumin on cell viability of GCT cells. Interesting, down-regulation of JNK protein expression could also reversed the anti-cancer effect of curcumin on cell viability of GCT cells. Taken together, our results suggest that curcumin inhibits cell proliferation and promotes apoptosis in osteoclastoma cell through suppression of MMP-9 and NF-κB, and activation JNK signaling pathways. PMID:26261481

  11. [Preparation and anti-cancer activity in vitro of curcumin loaded mesoporous silica nanoparticle].

    PubMed

    He, Li-li; Gu, Jian

    2015-11-01

    This paper is to prepare curcumin (Cur) loaded mesoporous silica nanoparticle (Cur-MSN), evaluate its release behavior and anti-cancer activity in vitro. Mesoporous silica nanoparticle (MSN) was prepared by polymerization method and Cur-MSN was obtained using solvent evaporation method and impregnation centrifugation method. The preparation method was optimized using entrapment efficiency (EE) and loading efficiency (LE) as indexes. Cur-MSN was characterized with scanning electron microscope and its particle size and zeta potential were determined. Finally, in vitro release behavior in 0.2% SDS solution and its cell-killing effect on HeLa cells were also evaluated. The Cur-MSN prepared with process optimization method was round and uniform and exhibited typical mesoporous characterization. The mean particle size and Zeta potential of Cur-MSN were 75.8 nm and -30.1 mV, respectively. EE and LE of three batches of Cur-MSN were (72.55 ± 2.01)% and (16.21 ± 1.12)%, respectively. In vitro release behavior of Cur-MSN showed a sustained release profile with 83.5% cumulative release within 96 h. The killing effect of Cur-MSN on HeLa cells was dose-dependent with IC50 of 19.40 mg x L(-1), which was similar to that of Cur. PMID:27071254

  12. Gelucire-Based Nanoparticles for Curcumin Targeting to Oral Mucosa: Preparation, Characterization, and Antimicrobial Activity Assessment.

    PubMed

    Hazzah, Heba A; Farid, Ragwa M; Nasra, Maha M A; Hazzah, Walaa A; El-Massik, Magda A; Abdallah, Ossama Y

    2015-11-01

    The purpose of the study was to prepare and characterize curcumin (Cur) solid lipid nanoparticles (CurSLN) with a high-loading capacity and chemical stability for the treatment of oral mucosal infection. CurSLN were formulated using different lipids, namely, Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and poloxamer 407 as a surfactant. Formulae were evaluated for their entrapment efficiency, particle size, and ex vivo mucoadhesion test. Microbiological evaluation was carried out on six microorganisms, five of which are the most commonly affecting oral cavity in terms of determination of minimum inhibitory concentration (MIC), and minimum bactericidal concentration. Transmission electron microscopy was conducted for ultrathin section for Candida albicans-treated with formulated Cur. The results showed high entrapment efficiency and stability enhancement for Cur powder. Significant amount of Cur was retained onto the mucosal tissue indicating preferential mucosal uptake. CurSLN showed higher antimicrobial activity as compared with Cur raw material and chemically stabilized Cur where it showed MIC (0.185, 0.09375, 0.75, 3, 1.5, and 0.1875 mg/mL) against Staphylococcus aureus, Streptococcus mutans, Viridansstrept, Escherichia coli, Lactobacillus acidophilus, and Candida albicans, respectively. The prepared lipid nanoparticles maintained Cur chemical stability and microbiological activity. The lack of local antimicrobial therapeutics with minimum side effects augments the importance of studying natural products for this purpose. PMID:26202796

  13. Photocatalytic performance of Ag doped SnO2 nanoparticles modified with curcumin

    NASA Astrophysics Data System (ADS)

    Vignesh, K.; Hariharan, R.; Rajarajan, M.; Suganthi, A.

    2013-07-01

    Visible light active Ag doped SnO2 nanoparticles modified with curcumin (Cur-Ag-SnO2) have been prepared by a combined precipitation and chemical impregnation route. The optical properties, phase structures and morphologies of the as-prepared nanoparticles were characterized using UV-visible diffuse reflectance spectra (UV-vis-DRS), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). The surface area was measured by Brunauer. Emmett. Teller (B.E.T) analysis. Compared to bare SnO2, the surface modified photocatalysts (Ag-SnO2 and Cur-Ag-SnO2) showed a red shift in the visible region. The photocatalytic activity was monitored via the degradation of rose bengal (RB) dye and the results revealed that Cur-Ag-SnO2 shows better photocatalytic activity than that of Ag-SnO2 and SnO2. The superior photocatalytic activity of Cur-Ag-SnO2 could be attributed to the effective electron-hole separation by surface modification. The effect of photocatalyst concentration, initial dye concentration and electron scavenger on the photocatalytic activity was examined in detail. Furthermore, the antifungal activity of the photocatalysts and the reusability of Cur-Ag-SnO2 were tested.

  14. Curcumin inhibited HGF-induced EMT and angiogenesis through regulating c-Met dependent PI3K/Akt/mTOR signaling pathways in lung cancer

    PubMed Central

    Jiao, Demin; Wang, Jian; Lu, Wei; Tang, Xiali; Chen, Jun; Mou, Hao; Chen, Qing-yong

    2016-01-01

    The epithelial-mesenchymal transition (EMT) and angiogenesis have emerged as two pivotal events in cancer progression. Curcumin has been extensively studied in preclinical models and clinical trials of cancer prevention due to its favorable toxicity profile. However, the possible involvement of curcumin in the EMT and angiogenesis in lung cancer remains unclear. This study found that curcumin inhibited hepatocyte growth factor (HGF)-induced migration and EMT-related morphological changes in A549 and PC-9 cells. Moreover, pretreatment with curcumin blocked HGF-induced c-Met phosphorylation and downstream activation of Akt, mTOR, and S6. These effects mimicked that of c-Met inhibitor SU11274 or PI3 kinase inhibitor LY294002 or mTOR inhibitor rapamycin treatment. c-Met gene overexpression analysis further demonstrated that curcumin suppressed lung cancer cell EMT by inhibiting c-Met/Akt/mTOR signaling pathways. In human umbilical vein endothelial cells (HUVECs), we found that curcumin also significantly inhibited PI3K/Akt/mTOR signaling and induced apoptosis and reduced migration and tube formation of HGF-treated HUVEC. Finally, in the experimental mouse model, we showed that curcumin inhibited HGF-stimulated tumor growth and induced an increase in E-cadherin expression and a decrease in vimentin, CD34, and vascular endothelial growth factor (VEGF) expression. Collectively, these findings indicated that curcumin could inhibit HGF-promoted EMT and angiogenesis by targeting c-Met and blocking PI3K/Akt/mTOR pathways. PMID:27525306

  15. Curcumin and Boswellia serrata gum resin extract inhibit chikungunya and vesicular stomatitis virus infections in vitro.

    PubMed

    von Rhein, Christine; Weidner, Tatjana; Henß, Lisa; Martin, Judith; Weber, Christopher; Sliva, Katja; Schnierle, Barbara S

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes chikungunya fever and has infected millions of people mainly in developing countries. The associated disease is characterized by rash, high fever, and severe arthritis that can persist for years. CHIKV has adapted to Aedes albopictus, which also inhabits temperate regions including Europe and the United States of America. CHIKV has recently caused large outbreaks in Latin America. No treatment or licensed CHIKV vaccine exists. Traditional medicines are known to have anti-viral effects; therefore, we examined whether curcumin or Boswellia serrata gum resin extract have antiviral activity against CHIKV. Both compounds blocked entry of CHIKV Env-pseudotyped lentiviral vectors and inhibited CHIKV infection in vitro. In addition, vesicular stomatitis virus vector particles and viral infections were also inhibited to the same extent, indicating a broad antiviral activity. Although the bioavailability of these compounds is rather poor, they might be used as a lead structure to develop more effective antiviral drugs or might be used topically to prevent CHIKV spread in the skin after mosquito bites. PMID:26611396

  16. Dietary curcumin counteracts extracellular transthyretin deposition: insights on the mechanism of amyloid inhibition.

    PubMed

    Ferreira, Nelson; Santos, Sónia A O; Domingues, Maria Rosário M; Saraiva, Maria João; Almeida, Maria Rosário

    2013-01-01

    The transthyretin amyloidoses (ATTR) are devastating diseases characterized by progressive neuropathy and/or cardiomyopathy for which novel therapeutic strategies are needed. We have recently shown that curcumin (diferuloylmethane), the major bioactive polyphenol of turmeric, strongly suppresses TTR fibril formation in vitro, either by stabilization of TTR tetramer or by generating nonfibrillar small intermediates that are innocuous to cultured neuronal cells. In the present study, we aim to assess the effect of curcumin on TTR amyloidogenesis in vivo, using a well characterized mouse model for familial amyloidotic polyneuropathy (FAP). Mice were given 2% (w/w) dietary curcumin or control diet for a six week period. Curcumin supplementation resulted in micromolar steady-state levels in plasma as determined by LC/MS/MS. We show that curcumin binds selectively to the TTR thyroxine-binding sites of the tetramer over all the other plasma proteins. The effect on plasma TTR stability was determined by isoelectric focusing (IEF) and curcumin was found to significantly increase TTR tetramer resistance to dissociation. Most importantly, immunohistochemistry (IHC) analysis of mice tissues demonstrated that curcumin reduced TTR load in as much as 70% and lowered cytotoxicity associated with TTR aggregation by decreasing activation of death receptor Fas/CD95, endoplasmic reticulum (ER) chaperone BiP and 3-nitrotyrosine in tissues. Taken together, our results highlight the potential use of curcumin as a lead molecule for the prevention and treatment of TTR amyloidosis. PMID:23069388

  17. Curcumin inhibits interferon-{alpha} induced NF-{kappa}B and COX-2 in human A549 non-small cell lung cancer cells

    SciTech Connect

    Lee, Jeeyun |; Im, Young-Hyuck | E-mail: imyh@smc.samsung.co.kr; Jung, Hae Hyun; Kim, Joo Hyun; Park, Joon Oh |; Kim, Kihyun |; Kim, Won Seog |; Ahn, Jin Seok

    2005-08-26

    The A549 cells, non-small cell lung cancer cell line from human, were resistant to interferon (IFN)-{alpha} treatment. The IFN-{alpha}-treated A549 cells showed increase in protein expression levels of NF-{kappa}B and COX-2. IFN-{alpha} induced NF-{kappa}B binding activity within 30 min and this increased binding activity was markedly suppressed with inclusion of curcumin. Curcumin also inhibited IFN-{alpha}-induced COX-2 expression in A549 cells. Within 10 min, IFN-{alpha} rapidly induced the binding activity of a {gamma}-{sup 32}P-labeled consensus GAS oligonucleotide probe, which was profoundly reversed by curcumin. Taken together, IFN-{alpha}-induced activations of NF-{kappa}B and COX-2 were inhibited by the addition of curcumin in A549 cells.

  18. Curcumin combined with FAPαc vaccine elicits effective antitumor response by targeting indolamine-2,3-dioxygenase and inhibiting EMT induced by TNF-α in melanoma.

    PubMed

    Jiang, Guan-Min; Xie, Wan-Ying; Wang, Hong-Sheng; Du, Jun; Wu, Bai-Ping; Xu, Wei; Liu, Hui-Fang; Xiao, Ping; Liu, Zhi-Gang; Li, Hong-Yan; Liu, Shuang-Quan; Yin, Wen-Jun; Zhang, Qiu-Gui; Liang, Jian-Ping; Huang, Hong-Jun

    2015-09-22

    Fibroblast activation protein α (FAPα) is a potential target for cancer therapy. However, elimination of FAPα+ fibroblasts activates secretion of IFN-γ and TNF-α. IFN-γ can in turn induce expression indolamine-2,3-dioxygenase (IDO), thereby contributing to immunosuppression, while TNF-α can induce EMT. These two reactive effects would limit the efficacy of a tumor vaccine. We found that curcumin can inhibit IDO expression and TNF-α-induced EMT. Moreover, FAPαc vaccine and CpG combined with curcumin lavage inhibited tumor growth and prolonged the survival of mice implanted with melanoma cells. The combination of FAPαc vaccine, CpG and curcumin stimulated FAPα antibody production and CD8+ T cell-mediated killing of FAPα-expressing stromal cells without adverse reactive effects. We suggest a combination of curcumin and FAPαc vaccine for melanoma therapy. PMID:26305550

  19. Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway.

    PubMed

    Tiwari, Shashi Kant; Agarwal, Swati; Tripathi, Anurag; Chaturvedi, Rajnish Kumar

    2016-07-01

    Bisphenol A (BPA) is an environmental xenoestrogenic endocrine disruptor, utilized for production of consumer products, and exerts adverse effects on the developing nervous system. Recently, we found that BPA impairs the finely tuned dynamic processes of neurogenesis (generation of new neurons) in the hippocampus of the developing rat brain. Curcumin is a natural polyphenolic compound, which provides neuroprotection against various environmental neurotoxicants and in the cellular and animal models of neurodegenerative disorders. Here, we have assessed the neuroprotective efficacy of curcumin against BPA-mediated reduced neurogenesis and the underlying cellular and molecular mechanism(s). Both in vitro and in vivo studies showed that curcumin protects against BPA-induced hippocampal neurotoxicity. Curcumin protects against BPA-mediated reduced neural stem cells (NSC) proliferation and neuronal differentiation and enhanced neurodegeneration. Curcumin also enhances the expression/levels of neurogenic and the Wnt pathway genes/proteins, which were reduced due to BPA exposure in the hippocampus. Curcumin-mediated neuroprotection against BPA-induced neurotoxicity involved activation of the Wnt/β-catenin signaling pathway, which was confirmed by the use of Wnt specific activators (LiCl and GSK-3β siRNA) and inhibitor (Dkk-1). BPA-mediated increased β-catenin phosphorylation, decreased GSK-3β levels, and β-catenin nuclear translocation were significantly reversed by curcumin, leading to enhanced neurogenesis. Curcumin-induced protective effects on neurogenesis were blocked by Dkk-1 in NSC culture treated with BPA. Curcumin-mediated enhanced neurogenesis was correlated well with improved learning and memory in BPA-treated rats. Overall, our results conclude that curcumin provides neuroprotection against BPA-mediated impaired neurogenesis via activation of the Wnt/β-catenin signaling pathway. PMID:25963729

  20. Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles.

    PubMed

    Lakshmi, Yeruva Samrajya; Kumar, Prashant; Kishore, Golla; Bhaskar, C; Kondapi, Anand K

    2016-01-01

    We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40-70 nm size, with encapsulation efficiency of 63 ± 1.9% of Cur &61.5% ± 1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59 ± 1.34%; EFV: 58.4 ± 1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88-124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39-4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV + Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6-3.0 fold in terms of IL-6 and TNF-α in vaginal tissue and plasma compared to soluble EFV + Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV + Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV + Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV. PMID:27151598

  1. Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles

    PubMed Central

    Lakshmi, Yeruva Samrajya; Kumar, Prashant; Kishore, Golla; Bhaskar, C; Kondapi, Anand K

    2016-01-01

    We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40–70 nm size, with encapsulation efficiency of 63 ± 1.9% of Cur & 61.5% ± 1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59 ± 1.34%; EFV: 58.4 ± 1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88–124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39–4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV + Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6–3.0 fold in terms of IL-6 and TNF-α in vaginal tissue and plasma compared to soluble EFV + Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV + Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV + Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV. PMID:27151598

  2. Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling

    PubMed Central

    DU, YUEFENG; LONG, QINGZHI; ZHANG, LIN; SHI, YING; LIU, XIOAGANG; LI, XUDONG; GUAN, BIN; TIAN, YANCHAO; WANG, XINYANG; LI, LEI; HE, DALIN

    2015-01-01

    Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer. PMID:26499200

  3. Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling.

    PubMed

    Du, Yuefeng; Long, Qingzhi; Zhang, Lin; Shi, Ying; Liu, Xioagang; Li, Xudong; Guan, Bin; Tian, Yanchao; Wang, Xinyang; Li, Lei; He, Dalin

    2015-12-01

    Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer. PMID:26499200

  4. Curcumin attenuates cyclooxygenase-2 expression via inhibition of the NF-κB pathway in lipopolysaccharide-stimulated human gingival fibroblasts.

    PubMed

    Hu, Ping; Huang, Ping; Chen, Min Wei

    2013-05-01

    Porphyromonas gingivalis lipopolysaccharide (LPS) induces the expression of the cyclooxygenase-2 (COX-2), which contributes to the process of periodontitis. Curcumin, a constituent of turmeric, exhibits anti-inflammatory properties. We have investigated the anti-inflammatory effect of curcumin in human gingival fibroblasts (HGFs) stimulated by P. gingivalis LPS and its mechanism of action. HGFs pretreated with curcumin were stimulated by P. gingivalis LPS. COX-2 mRNA and protein expressions were analysed by real-time PCR and Western blot analysis. Activation of nuclear factor kappa B (NF-κB) was analysed by the NF-κB-dependent luciferase activity and electrophoretic mobility-shift assay (EMSA). Curcumin inhibited COX-2 mRNA and protein synthesis in LPS-stimulated HGFs in a dose-dependent manner. P. gingivalis LPS activated NF-κB-dependent transcription in HGFs, which were also downregulated by pretreatment with curcumin. Therefore, curcumin can inhibit P. gingivalis LPS-induced COX-2 expression, which may be due to the inhibition of the NF-κB pathway. PMID:23494805

  5. Pyridine analogues of curcumin exhibit high activity for inhibiting CWR-22Rv1 human prostate cancer cell growth and androgen receptor activation

    PubMed Central

    ZHOU, DAI-YING; ZHAO, SU-QING; DU, ZHI-YUN; ZHENG, XI; ZHANG, KUN

    2016-01-01

    The concentrations required for curcumin to exert its anticancer activity (IC50, 20 µM) are difficult to achieve in the blood plasma of patients, due to the low bioavailability of the compound. Therefore, much effort has been devoted to the development of curcumin analogues that exhibit stronger anticancer activity and a lower IC50 than curcumin. The present study investigated twelve pyridine analogues of curcumin, labeled as groups AN, BN, EN and FN, to determine their effects in CWR-22Rv1 human prostate cancer cells. The inhibitory effects of these compounds on testosterone (TT)-induced androgen receptor (AR) activity was determined by performing an AR-linked luciferase assay and by TT-induced expression of prostate-specific antigen. The results of the current study suggested that the FN group of analogues had the strongest inhibitory effect of growth on CWR-22Rv1 cultured cells, and were the most potent inhibitor of AR activity compared with curcumin, and the AN, BN and EN analogues. Thus, the results of the present study indicate the inhibition of the AR pathways as a potential mechanism for the anticancer effect of curcumin analogues in human prostate cancer cells. Furthermore, curcumin analogues with pyridine as a distal ring and tetrahydrothiopyran-4-one as a linker may be good candidates for the development of novel drugs for the treatment of prostate cancer, by targeting the AR signaling pathway. PMID:27313760

  6. Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway.

    PubMed

    Dai, Chongshan; Li, Daowen; Gong, Lijing; Xiao, Xilong; Tang, Shusheng

    2016-01-01

    Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications. PMID:27556439

  7. Selenium nanoparticles inhibit Staphylococcus aureus growth

    PubMed Central

    Tran, Phong A; Webster, Thomas J

    2011-01-01

    Staphylococcus aureus is a key bacterium commonly found in numerous infections. S. aureus infections are difficult to treat due to their biofilm formation and documented antibiotic resistance. While selenium has been used for a wide range of applications including anticancer applications, the effects of selenium nanoparticles on microorganisms remain largely unknown to date. The objective of this in vitro study was thus to examine the growth of S. aureus in the presence of selenium nanoparticles. Results of this study provided the first evidence of strongly inhibited growth of S. aureus in the presence of selenium nanoparticles after 3, 4, and 5 hours at 7.8, 15.5, and 31 μg/mL. The percentage of live bacteria also decreased in the presence of selenium nanoparticles. Therefore, this study suggests that selenium nanoparticles may be used to effectively prevent and treat S. aureus infections and thus should be further studied for such applications. PMID:21845045

  8. Poly(D,L-lactic acid)-glycerol-based nanoparticles for curcumin delivery.

    PubMed

    Yoon, In-Soo; Park, Ju-Hwan; Kang, Hyo Jin; Choe, Ji Hyeong; Goh, Min Su; Kim, Dae-Duk; Cho, Hyun-Jong

    2015-07-01

    Poly(D,L-lactic acid)-glycerol (PDLLA-G)-based nanoparticles (NPs) were fabricated for the intravenous delivery of curcumin (CUR). NPs with a mean diameter of approximately 200 nm, a narrow size distribution, and capable of efficient drug encapsulation were prepared using an emulsification-solvent evaporation method. The stability of NPs was verified in water, phosphate buffered saline (PBS), and serum after 24-h incubation. A sustained drug release pattern was observed, and the amount of CUR released in acidic media (pH 5.5) was higher than in media at physiological pH (pH 7.4). Blank NPs (without drug loading) did not exhibit severe cytotoxicity in MDA-MB-231 human breast adenocarcinoma cells. The in vitro anti-tumor efficacy of CUR-loaded NPs in MDA-MB-231 cells was comparable to that of a solution of CUR. Pharmacokinetic studies in rats showed that the in vivo clearance (CL) of CUR in the NP-treated group was lower than the group treated with CUR solution. Therefore, encapsulation of CUR in PDLLA-G NPs was shown to enable prolonged circulation of the drug in the blood stream and guarantee improved anticancer activity after intravenous injection. These biocompatible NPs could be an efficient nano-sized injectable formulation for CUR delivery. PMID:25900098

  9. Curcumin inhibits tumor epithelial-mesenchymal transition by downregulating the Wnt signaling pathway and upregulating NKD2 expression in colon cancer cells

    PubMed Central

    ZHANG, ZEWEI; CHEN, HAITAO; XU, CHAO; SONG, LU; HUANG, LULU; LAI, YUEBIAO; WANG, YUQI; CHEN, HANLU; GU, DANLIN; REN, LILI; YAO, QINGHUA

    2016-01-01

    Tumor invasion and metastasis are closely associated with epithelial-mesenchymal transition (EMT). EMT refers to epithelial cells under physiological and pathological conditions that are specific to mesenchymal transition. Curcumin inhibits EMT progression via Wnt signaling. The Wnt signaling pathway is a conservative EMT-related signaling pathway that is involved in the development of various tumors. In the present study, MTS assays were employed to analyze the proliferation of curcumin-treated cells. Naked cuticle homolog 2 (NKD2), chemokine receptor 4 (CXCR4) and antibodies associated with EMT were examined in SW620 colorectal cancer cell lines using western blot analysis and real-time qPCR. NKD2 small-interfering RNA (siRNA) and CXCR4 expression plasmid was synthesized and transfected into the colorectal cancer cell lines, and NKD2 and CXCR4 expression levels were detected. The results showed that curcumin significantly inhibited the proliferation of colorectal cancer cells and upregulated the expression of NKD2 in SW620 colorectal cancer cells and in the xenograft, resulting in the downregulation of key markers in the Wnt signaling. In addition, the progression of ETM was inhibited due to the overexpression of E-cadherin as well as the downregulation of vimentin. Curcumin also inhibited tumor metastasis by downregulating the expression of CXCR4 significantly. The results suggested involvement of the NKD2-Wnt-CXCR4 signaling pathway in colorectal cancer cells. In addition, curcumin is inhibit this signaling and the development of colorectal cancer. PMID:26985708

  10. Liposome encapsulated curcumin-difluorinated (CDF) inhibits the growth of cisplatin resistant head and neck cancer stem cells.

    PubMed

    Basak, Saroj K; Zinabadi, Alborz; Wu, Arthur W; Venkatesan, Natarajan; Duarte, Victor M; Kang, James J; Dalgard, Clifton L; Srivastava, Meera; Sarkar, Fazlul H; Wang, Marilene B; Srivatsan, Eri S

    2015-07-30

    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with 600,000 new cases every year worldwide. Although chemotherapeutics exist, five-year survival is only 50%. New strategies to overcome drug resistance are required to improve HNSCC treatment. Curcumin-difluorinated (CDF), a synthetic analog of curcumin, was packaged in liposomes and used to evaluate growth inhibition of cisplatin resistant HNSCC cell lines CCL-23R and UM-SCC-1R generated from the parental cell lines CCL-23 and UM-SCC-1 respectively. Growth inhibition in vitro and expression levels of the CD44 (cancer stem cell marker), cytokines, and growth factors were investigated after liposomal CDF treatment. The in vivo growth inhibitory effect of liposomal CDF was evaluated in the nude mice xenograft tumor model of UM-SCC-1R and the inhibition of CD44 was measured. Treatment of the resistant cell lines in vitro with liposomal CDF resulted in a statistically significant growth inhibition (p < 0.05). The nude mice xenograft study showed a statistically significant tumor growth inhibition of UM-SCC-1R cells and a reduction in the expression of CD44 (p < 0.05), indicating an inhibitory effect of liposomal CDF on CSCs. Our results demonstrate that delivery of CDF through liposomes may be an effective method for the treatment of cisplatin resistant HNSCC. PMID:26098778

  11. Xanthan gum stabilized PEGylated gold nanoparticles for improved delivery of curcumin in cancer

    NASA Astrophysics Data System (ADS)

    Swami Muddineti, Omkara; Kumari, Preeti; Ajjarapu, Srinivas; Manish Lakhani, Prit; Bahl, Rishabh; Ghosh, Balaram; Biswas, Swati

    2016-08-01

    In recent years, gold nanoparticles (AuNPs) have received immense interest in various biomedical applications including drug delivery, photothermal ablation of cancer and imaging agent for cancer diagnosis. However, the synthesis of AuNPs poses challenges due to the poor reproducibility and stability of the colloidal system. In the present work, we developed a one step, facile procedure for the synthesis of AuNPs from hydrogen tetrachloroaurate (III) hydrate (HAuCl4. 3H2O) by using ascorbic acid and xanthan gum (XG) as reducing agent and stabilizer, respectively. The effect of concentrations of HAuCl4, 3H2O, ascorbic acid and methoxy polyethylene glycol-thiol (mPEG800-SH) were optimized and it was observed that stable AuNPs were formed at concentrations of 0.25 mM, 50 μM and 1 mM for HAuCl4.3H2O, ascorbic acid, and mPEG800-SH, respectively. The XG stabilized, deep red wine colored AuNPs (XG-AuNPs) were obtained by drop-wise addition of aqueous solution of ascorbic acid (50 mM) and XG (1.5 mg ml‑1). Synthesized XG-AuNPs showed λmax at 540 nm and a mean hydrodynamic diameter of 80 ± 3 nm. PEGylation was performed with mPEG800-SH to obtain PEGylated XG-AuNPs (PX-AuNPs) and confirmed by Ellman’s assay. No significant shift observed in λmax and hydrodynamic diameter between XG-AuNPs and PX-AuNPs. Colloidal stability of PX-AuNPs was studied in normal saline, buffers within a pH range of 1.2–7.4, DMEM complete medium and in normal storage condition at 4 ˚C. Further, water soluble curcumin was prepared using PVP-K30 as solid dispersion and loaded on to PX-AuNPs (CPX-AuNPs), and evaluated for cellular uptake and cytotoxicity in Murine melanoma (B16F10) cells. Time and concentration dependent studies using CPX-AuNPs showed efficient uptake and decreased cell viability compared to free curcumin.

  12. Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

    PubMed Central

    Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

    2016-01-01

    Purpose Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Methods Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Results Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. Conclusion These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve

  13. Xanthan gum stabilized PEGylated gold nanoparticles for improved delivery of curcumin in cancer.

    PubMed

    Muddineti, Omkara Swami; Kumari, Preeti; Ajjarapu, Srinivas; Lakhani, Prit Manish; Bahl, Rishabh; Ghosh, Balaram; Biswas, Swati

    2016-08-12

    In recent years, gold nanoparticles (AuNPs) have received immense interest in various biomedical applications including drug delivery, photothermal ablation of cancer and imaging agent for cancer diagnosis. However, the synthesis of AuNPs poses challenges due to the poor reproducibility and stability of the colloidal system. In the present work, we developed a one step, facile procedure for the synthesis of AuNPs from hydrogen tetrachloroaurate (III) hydrate (HAuCl4. 3H2O) by using ascorbic acid and xanthan gum (XG) as reducing agent and stabilizer, respectively. The effect of concentrations of HAuCl4, 3H2O, ascorbic acid and methoxy polyethylene glycol-thiol (mPEG800-SH) were optimized and it was observed that stable AuNPs were formed at concentrations of 0.25 mM, 50 μM and 1 mM for HAuCl4.3H2O, ascorbic acid, and mPEG800-SH, respectively. The XG stabilized, deep red wine colored AuNPs (XG-AuNPs) were obtained by drop-wise addition of aqueous solution of ascorbic acid (50 mM) and XG (1.5 mg ml(-1)). Synthesized XG-AuNPs showed λmax at 540 nm and a mean hydrodynamic diameter of 80 ± 3 nm. PEGylation was performed with mPEG800-SH to obtain PEGylated XG-AuNPs (PX-AuNPs) and confirmed by Ellman's assay. No significant shift observed in λmax and hydrodynamic diameter between XG-AuNPs and PX-AuNPs. Colloidal stability of PX-AuNPs was studied in normal saline, buffers within a pH range of 1.2-7.4, DMEM complete medium and in normal storage condition at 4 ˚C. Further, water soluble curcumin was prepared using PVP-K30 as solid dispersion and loaded on to PX-AuNPs (CPX-AuNPs), and evaluated for cellular uptake and cytotoxicity in Murine melanoma (B16F10) cells. Time and concentration dependent studies using CPX-AuNPs showed efficient uptake and decreased cell viability compared to free curcumin. PMID:27348749

  14. Curcumin Inhibits The Adverse Effects of Sodium Arsenite in Mouse Epididymal Sperm

    PubMed Central

    Momeni, Hamid Reza; Eskandari, Najmeh

    2016-01-01

    Background The aim of this study was to investigate the effects of curcumin on epididy- mal sperm parameters in adult male Navel Medical Research Institute (NMRI) mice ex- posed to sodium arsenite. Materials and Methods In this experimental study, we divided the animals into four groups: control, sodium arsenite (5 mg/kg), curcumin (100 mg/kg) and curcumin+sodium arsenite. Exposures were performed by intraperitoneal injections for a 5-week period. After the exposure period, we recorded the animals’ body and left testes weights. The left caudal epididymis was used to count the sperm number and analyze motility, viability, morphological abnormalities, acrosome reaction, DNA integrity, and histone-protamine replacement in the spermatozoa. One-way analysis of variance (ANOVA) followed by the Tukey’s test was used to assess the statistical significance of the data with SPSS 16.0. P<0.05 was considered significant. Results Mice exposed to sodium arsenite showed a significant decrease in the num- ber, motility, viability, normal sperm morphology and acrosome integrity of spermato- zoa compared to the control group. In the curcumin+sodium arsenite group, curcumin significantly reversed these adverse effects to the point where they approximated the control. In addition, the application of curcumin alone had no significant difference in these parameters compared to the control and curcumin+sodium arsenite groups. However, we observed no significant differences in the body and the testis weight as well as the DNA integrity and histone-protamine replacement in the spermatozoa of the four groups. Conclusion Curcumin compensated for the toxic effects of sodium arsenite on a number of sperm parameters in adult mice. PMID:27441059

  15. Core-Shell Soy Protein-Soy Polysaccharide Complex (Nano)particles as Carriers for Improved Stability and Sustained Release of Curcumin.

    PubMed

    Chen, Fei-Ping; Ou, Shi-Yi; Tang, Chuan-He

    2016-06-22

    Using soy protein isolate (SPI) and soy-soluble polysaccharides (SSPS) as polymer matrixes, this study reported a novel process to fabricate unique core-shell complex (nano)particles to perform as carriers for curcumin (a typical poorly soluble bioactive). In the process, curcumin-SPI nanocomplexes were first formed at pH 7.0 and then coated by SSPS. At this pH, the core-shell complex was formed in a way the SPI nanoparticles might be incorporated into the interior of SSPS molecules without distinctly affecting the size and morphology of particles. The core-shell structure was distinctly changed by adjusting pH from 7.0 to 4.0. At pH 4.0, SSPS was strongly bound to the surface of highly aggregated SPI nanoparticles, and as a consequence, much larger complexes were formed. The bioaccessibility of curcumin in the SPI-curcumin complexes was unaffected by the SSPS coating. However, the core-shell complex formation greatly improved the thermal stability and controlled release properties of encapsulated curcumin. The improvement was much better at pH 4.0 than that at pH 7.0. All of the freeze-dried core-shell complex preparations exhibited good redispersion behavior. The findings provide a simple approach to fabricate food-grade delivery systems for improved water dispersion, heat stability, and even controlled release of poorly soluble bioactives. PMID:27243766

  16. Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer's disease mice using magnetic resonance imaging (MRI).

    PubMed

    Cheng, Kwok Kin; Chan, Pui Shan; Fan, Shujuan; Kwan, Siu Ming; Yeung, King Lun; Wáng, Yì-Xiáng J; Chow, Albert Hee Lum; Wu, Ed X; Baum, Larry

    2015-03-01

    Diagnosis of Alzheimer's disease (AD) can be performed with the assistance of amyloid imaging. The current method relies on positron emission tomography (PET), which is expensive and exposes people to radiation, undesirable features for a population screening method. Magnetic resonance imaging (MRI) is cheaper and is not radioactive. Our approach uses magnetic nanoparticles (MNPs) made of superparamagnetic iron oxide (SPIO) conjugated with curcumin, a natural compound that specifically binds to amyloid plaques. Coating of curcumin-conjugated MNPs with polyethylene glycol-polylactic acid block copolymer and polyvinylpyrrolidone by antisolvent precipitation in a multi-inlet vortex mixer produces stable and biocompatible curcumin magnetic nanoparticles (Cur-MNPs) with mean diameter <100 nm. These nanoparticles were visualized by transmission electron microscopy and atomic force microscopy, and their structure and chemistry were further characterized by X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and Fourier transform infrared spectroscopy. Cur-MNPs exhibited no cytotoxicity in either Madin-Darby canine kidney (MDCK) or differentiated human neuroblastoma cells (SH-SY5Y). The Papp of Cur-MNPs was 1.03 × 10(-6) cm/s in an in vitro blood-brain barrier (BBB) model. Amyloid plaques could be visualized in ex vivo T2*-weighted magnetic resonance imaging (MRI) of Tg2576 mouse brains after injection of Cur-MNPs, and no plaques could be found in non-transgenic mice. Immunohistochemical examination of the mouse brains revealed that Cur-MNPs were co-localized with amyloid plaques. Thus, Cur-MNPs have the potential for non-invasive diagnosis of AD using MRI. PMID:25617135

  17. Metabolic and pharmacokinetic studies of curcumin, demethoxycurcumin and bisdemethoxycurcumin in mice tumor after intragastric administration of nanoparticle formulations by liquid chromatography coupled with tandem mass spectrometry.

    PubMed

    Li, Rui; Qiao, Xue; Li, Qingyan; He, Rong; Ye, Min; Xiang, Cheng; Lin, Xionghao; Guo, Dean

    2011-09-15

    This paper aims to investigate the metabolism and pharmacokinetics of curcumin, demethoxycurcumin and bisdemethoxycurcumin in mice tumor. To improve water solubility, nanoparticle formulations were prepared as curcuminoids-loaded solid lipid nanoparticles (curcuminoids-SLNs) and curcumin-loaded solid lipid nanoparticles (curcumin-SLNs). After intragastric administration to tumor-bearing ICR mice, the plasma and tumor samples were analyzed by liquid chromatography with ion trap mass spectrometry. We discovered that curcuminoids were mainly present as glucuronides in plasma, whereas in free form in tumor tissue. A validated LC/MS/MS method was established to determine the three free curcuminoids in tumor homogenate. Samples were separated on a Zorbax SB-C(18) column, eluted with acetonitrile-water (containing 0.1% formic acid), and detected by TSQ Quantum triple quadrupole mass spectrometer in selected reaction monitoring mode. The method showed good linearity (r(2)=0.997-0.999) over wide dynamic ranges (2-6000 ng/mL). Variations within- and between-batch never exceeded 11.2% and 13.4%, respectively. The extraction recovery rates ranged from 78.3% to 87.7%. The pharmacokinetics of curcuminoids in mice tumor fit two-compartment model and first order elimination. For curcumin-SLNs group, the dosing of 250 mg/kg of curcumin resulted in AUC((0-48 h)) of 2285 ngh/mL and C(max) of 209 ng/mL. For curcuminoids-SLNs group, the dosing equivalent to 138 mg/kg of curcumin resulted in higher tumor concentrations (AUC=2811 ngh/mL, C(max)=285 ng/mL). It appeared that co-existing curcuminoids improved the bioavailability of curcumin. PMID:21856253

  18. Inhibition of NF-κB translocation by curcumin analogs induces G0/G1 arrest and downregulates thymidylate synthase in colorectal cancer.

    PubMed

    Rajitha, Balney; Belalcazar, Astrid; Nagaraju, Ganji Purnachandra; Shaib, Walid L; Snyder, James P; Shoji, Mamoru; Pattnaik, Subasini; Alam, Afroz; El-Rayes, Bassel F

    2016-04-10

    Cell cycle progression and DNA synthesis are essential steps in cancer cell growth and resistance. Thymidylate synthase (TS) is a therapeutic target for 5FU. Curcumin is a potent inhibitor of NF-κB. EF31 and UBS109 are potent synthetic analogues of curcumin. We tested the hypothesis that inhibition of NF-κB translocation by curcumin and its analogs EF31 and UBS109 can inhibit cell cycle progression and downregulate TS levels in colorectal cancer (CRC) cell lines. Two CRC cell lines (HCT116 and HT-29) were either untreated (control) or treated with IC50 concentrations of curcumin, EF31 UBS109 led to G0/G1 cell cycle arrest. Treatment with curcumin, EF31 or UBS109 inhibited NF-κB, downregulated survival pathways and inhibited cell cycle progression. Arrest in the G0/G1 phase was associated with downregulation of the transcription factor E2F-1 and its target gene TS. NF-κB over-expression induced E2F-1 and TS protein and mRNA levels in both cell lines. EF31 and UBS109 treatment significantly decreased tumor growth in compared to untreated tumors. EF31 and UBS109 are promising agents for the prevention and treatment of CRC. PMID:26850372

  19. Curcumin inhibits invasive capabilities through epithelial mesenchymal transition in breast cancer cell lines.

    PubMed

    Gallardo, Marcela; Calaf, Gloria M

    2016-09-01

    Curcumin (diferuloyl methane) is an antioxidant that exerts antiproliferative and apoptotic effects and has anti-invasive and anti-metastatic properties. Evidence strongly implicates that epithelial-mesenchymal transition (EMT) is involved in malignant progression affecting genes such as Slug, AXL and Twist1. These genes are abnormally expressed in many tumors and favor metastasis. The purpose of this study was to determine the potential effect of curcumin on EMT, migration and invasion. Triple-positive and triple-negative breast cancer cell lines for estrogen receptor (ER), progesterone receptor (PgR) and HER/neu were used: i) MCF-10F, a normal immortalized breast epithelial cell line (negative), ii) Tumor2, a malignant and tumorigenic cell line (positive) derived from Alpha5 cell line injected into the immunologically depressed mice and transformed by 60/60 cGy doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation and estrogen, and iii) a commercially available MDA-MB‑231 (negative). The effect of curcumin (30 µM for 48 h) was evaluated on expression of EMT-related genes by RT-qPCR. Results showed that curcumin decreased E-cadherin, N-cadherin, β-catenin, Slug, AXL, Twist1, Vimentin and Fibronectin protein expression, independently of the positivity of the markers in the cell lines. Curcumin also decreased migration and invasive capabilities in comparison to their own controls. It can be concluded that curcumin influenced biochemical changes associated with EMT-related genes that seems to promote such transition and are at the core of several signaling pathways that mediate the transition. Thus, it can be suggested that curcumin is able to prevent or delay cancer progression through the interruption of this process. PMID:27573203

  20. Curcumin Pyrazole and its derivative (N-(3-Nitrophenylpyrazole) Curcumin inhibit aggregation, disrupt fibrils and modulate toxicity of Wild type and Mutant α-Synuclein

    PubMed Central

    Ahsan, Nuzhat; Mishra, Satyendra; Jain, Manish Kumar; Surolia, Avadhesha; Gupta, Sarika

    2015-01-01

    Accumulating evidence suggests that deposition of neurotoxic α-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson’s disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties. This study focuses on the inhibitory effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin isoxazole and their derivatives against α-synuclein aggregation, fibrillization and toxicity. Employing biochemical, biophysical and cell based assays we discovered that curcumin pyrazole (3) and its derivative N-(3-Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only arresting fibrillization and disrupting preformed fibrils but also preventing formation of A11 conformation in the protein that imparts toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of α-synuclein. These two analogues of curcumin described here may therefore be useful therapeutic inhibitors for the treatment of α-synuclein amyloidosis and toxicity in Parkinson’s disease and other synucleinopathies. PMID:25985292

  1. Curcumin nanoparticles loaded hydrogels protects against aflatoxin B1-induced genotoxicity in rat liver.

    PubMed

    Abdel-Wahhab, Mosaad A; Salman, Asmaa S; Ibrahim, Mohamed I M; El-Kady, Ahmed A; Abdel-Aziem, Sekena H; Hassan, Nabila S; Waly, Ahmed I

    2016-08-01

    The current study aimed to evaluate the protective role of curcumin nanoparticles loaded hydrogels (Cur-NPs-Hgs) against AFB1-induced genotoxicity in rat liver. Animals were divided into 7 treatment groups and treated orally for 3 weeks as follow: the control group, the group treated with Hgs alone (0.5 ml/rat), the groups treated with low or high dose of Cur-NPs-Hgs (100 or 200 mg/kg b.w), the group treated with AFB1 (0.125 mg/kg b.w) and the groups treated with AFB1 plus the low or high dose of Cur-NPs-Hgs. Blood ant liver samples were collected for different biochemical, genetical, histological and histochemical analysis. The results revealed that the prepared Cur-NPs have nearly spherical shape with average size of 140 ± 20 nm and negative zeta potential value of 30.7 ± 2.57 mV. The in vivo results showed that treatment with AFB1 decreased the body weight accompanied biochemical, genotoxicity and histological disturbances. The combined treatment with AFB1 and Cur-Nps-Hgs at the two tested doses succeeded to induce a significant protection against AFB1. It could be concluded that Cur-NPs-Hgs is a promise candidate to protect against AFB1-induce liver damage in the high incidence area. Moreover, Hgs are excellent candidates as drug delivery system. PMID:27288928

  2. Novel curcumin-loaded human serum albumin nanoparticles surface functionalized with folate: characterization and in vitro/vivo evaluation.

    PubMed

    Song, Zhiwang; Lu, Yonglin; Zhang, Xia; Wang, Haiping; Han, Junyi; Dong, Chunyan

    2016-01-01

    Folate-conjugated, curcumin-loaded human serum albumin nanoparticles (F-CM-HSANPs) were obtained by the chemical conjugation of folate to the surface of the curcumin (CM)-loaded human serum albumin nanoparticles (NPs). The NPs were characterized by various parameters, including size, polydispersity, zeta potential, morphology, encapsulation efficiency, and drug release profile. The mean particle size of F-CM-HSANPs was 165.6±15.7 nm (polydispersity index <0.28), and the average encapsulation efficiency percentage and drug loading percentage of the F-CM-HSANPs were 88.7%±4.8% and 7.9%±0.4%, respectively. Applied in vitro, the CM NPs, after conjugation with folate, maintained sustained release, and a faster release of CM was more visibly observed than the unconjugated NPs. F-CM-HSANPs can prolong the retention time of CM significantly in vivo. However, after intravenous injection of F-CM-HSANPs, the pharmacokinetic parameters of CM were not significantly different from those of CM-loaded human serum albumin NPs. The improved antitumor activity of F-CM-HSANPs may be attributable to the protection of drug from enzymatic deactivation followed by the selective localization at the desired site. These results suggest that the intravenous injection of F-CM-HSANPs is likely to have an advantage in the current clinical CM formulation, because it does not require the use of a solubilization agent and it is better able to target the tumor tissue. PMID:27574403

  3. Novel curcumin-loaded human serum albumin nanoparticles surface functionalized with folate: characterization and in vitro/vivo evaluation

    PubMed Central

    Song, Zhiwang; Lu, Yonglin; Zhang, Xia; Wang, Haiping; Han, Junyi; Dong, Chunyan

    2016-01-01

    Folate-conjugated, curcumin-loaded human serum albumin nanoparticles (F-CM-HSANPs) were obtained by the chemical conjugation of folate to the surface of the curcumin (CM)-loaded human serum albumin nanoparticles (NPs). The NPs were characterized by various parameters, including size, polydispersity, zeta potential, morphology, encapsulation efficiency, and drug release profile. The mean particle size of F-CM-HSANPs was 165.6±15.7 nm (polydispersity index <0.28), and the average encapsulation efficiency percentage and drug loading percentage of the F-CM-HSANPs were 88.7%±4.8% and 7.9%±0.4%, respectively. Applied in vitro, the CM NPs, after conjugation with folate, maintained sustained release, and a faster release of CM was more visibly observed than the unconjugated NPs. F-CM-HSANPs can prolong the retention time of CM significantly in vivo. However, after intravenous injection of F-CM-HSANPs, the pharmacokinetic parameters of CM were not significantly different from those of CM-loaded human serum albumin NPs. The improved antitumor activity of F-CM-HSANPs may be attributable to the protection of drug from enzymatic deactivation followed by the selective localization at the desired site. These results suggest that the intravenous injection of F-CM-HSANPs is likely to have an advantage in the current clinical CM formulation, because it does not require the use of a solubilization agent and it is better able to target the tumor tissue. PMID:27574403

  4. The inhibition of PI3K and NFκB promoted curcumin-induced cell cycle arrest at G2/M via altering polyamine metabolism in Bcl-2 overexpressing MCF-7 breast cancer cells.

    PubMed

    Berrak, Özge; Akkoç, Yunus; Arısan, Elif Damla; Çoker-Gürkan, Ajda; Obakan-Yerlikaya, Pınar; Palavan-Ünsal, Narçin

    2016-02-01

    Bcl-2 protein has been contributed with number of genes which are involved in oncogenesis. Among the many targets of Bcl-2, NFκB have potential role in induction of cell cycle arrest. Curcumin has potential therapeutic effects against breast cancer through multiple signaling pathways. In this study, we investigated the role of curcumin in induction of cell cycle arrest via regulating of NFκB and polyamine biosynthesis in wt and Bcl-2+ MCF-7 cells. To examine the effect of curcumin on cell cycle regulatory proteins, PI3K/Akt, NFκB pathways and polyamine catabolism, we performed immunoblotting assay. In addition, cell cycle analysis was performed by flow cytometry. The results indicated that curcumin induced cell cycle arrest at G2/M phase by downregulation of cyclin B1 and Cdc2 and inhibited colony formation in MCF-7wt cells. However, Bcl-2 overexpression prevented the inhibition of cell cycle associated proteins after curcumin treatment. The combination of LY294002, PI3K inhibitor, and curcumin induced cell cycle arrest by decreasing CDK4, CDK2 and cyclin E2 in Bcl-2+ MCF-7 cells. Moreover, LY294002 further inhibited the phosphorylation of Akt in Bcl-2+ MCF-7 cells. Curcumin could suppress the nuclear transport of NFκB through decreasing the interaction of P-IκB-NFκB. The combination of wedelolactone, NFκB inhibitor, and curcumin acted different on SSAT expression in wt MCF-7 and Bcl-2+ MCF-7 cells. NFκB inhibition increased the SSAT after curcumin treatment in Bcl-2 overexpressed MCF-7 cells. Inhibition of NFκB activity as well as suppression of ROS generation with NAC resulted in the partial relief of cells from G2/M checkpoint after curcumin treatment in wt MCF-7 cells. In conclusion, the potential role of curcumin in induction of cell cycle arrest is related with NFκB-regulated polyamine biosynthesis. PMID:26796279

  5. Curcumin Inhibits Angiogenesis and Adipogenesis in Cell Culture System and in Mice Fed High Fat Diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Angiogenesis is necessary for the growth of adipose tissue. Dietary polyphenols may suppress growth of adipose tissue through their antiangiogenic activity and by modulating adipocyte metabolism. In the present study, we examined the effect of curcumin on angiogenesis and adipocyte development in a ...

  6. Structurally Modified Curcumin Analogs Inhibit STAT3 Phosphorylation and Promote Apoptosis of Human Renal Cell Carcinoma and Melanoma Cell Lines

    PubMed Central

    Bill, Matthew A.; Nicholas, Courtney; Mace, Thomas A.; Etter, Jonathan P.; Li, Chenglong; Schwartz, Eric B.; Fuchs, James R.; Young, Gregory S.; Lin, Li; Lin, Jiayuh; He, Lei; Phelps, Mitch; Li, Pui-Kai; Lesinski, Gregory B.

    2012-01-01

    The Janus kinase-2 (Jak2)-signal transducer and activator of transcription-3 (STAT3) pathway is critical for promoting an oncogenic and metastatic phenotype in several types of cancer including renal cell carcinoma (RCC) and melanoma. This study describes two small molecule inhibitors of the Jak2-STAT3 pathway, FLLL32 and its more soluble analog, FLLL62. These compounds are structurally distinct curcumin analogs that bind selectively to the SH2 domain of STAT3 to inhibit its phosphorylation and dimerization. We hypothesized that FLLL32 and FLLL62 would induce apoptosis in RCC and melanoma cells and display specificity for the Jak2-STAT3 pathway. FLLL32 and FLLL62 could inhibit STAT3 dimerization in vitro. These compounds reduced basal STAT3 phosphorylation (pSTAT3), and induced apoptosis in four separate human RCC cell lines and in human melanoma cell lines as determined by Annexin V/PI staining. Apoptosis was also confirmed by immunoblot analysis of caspase-3 processing and PARP cleavage. Pre-treatment of RCC and melanoma cell lines with FLLL32/62 did not inhibit IFN-γ-induced pSTAT1. In contrast to FLLL32, curcumin and FLLL62 reduced downstream STAT1-mediated gene expression of IRF1 as determined by Real Time PCR. FLLL32 and FLLL62 significantly reduced secretion of VEGF from RCC cell lines in a dose-dependent manner as determined by ELISA. Finally, each of these compounds inhibited in vitro generation of myeloid-derived suppressor cells. These data support further investigation of FLLL32 and FLLL62 as lead compounds for STAT3 inhibition in RCC and melanoma. PMID:22899991

  7. Structurally modified curcumin analogs inhibit STAT3 phosphorylation and promote apoptosis of human renal cell carcinoma and melanoma cell lines.

    PubMed

    Bill, Matthew A; Nicholas, Courtney; Mace, Thomas A; Etter, Jonathan P; Li, Chenglong; Schwartz, Eric B; Fuchs, James R; Young, Gregory S; Lin, Li; Lin, Jiayuh; He, Lei; Phelps, Mitch; Li, Pui-Kai; Lesinski, Gregory B

    2012-01-01

    The Janus kinase-2 (Jak2)-signal transducer and activator of transcription-3 (STAT3) pathway is critical for promoting an oncogenic and metastatic phenotype in several types of cancer including renal cell carcinoma (RCC) and melanoma. This study describes two small molecule inhibitors of the Jak2-STAT3 pathway, FLLL32 and its more soluble analog, FLLL62. These compounds are structurally distinct curcumin analogs that bind selectively to the SH2 domain of STAT3 to inhibit its phosphorylation and dimerization. We hypothesized that FLLL32 and FLLL62 would induce apoptosis in RCC and melanoma cells and display specificity for the Jak2-STAT3 pathway. FLLL32 and FLLL62 could inhibit STAT3 dimerization in vitro. These compounds reduced basal STAT3 phosphorylation (pSTAT3), and induced apoptosis in four separate human RCC cell lines and in human melanoma cell lines as determined by Annexin V/PI staining. Apoptosis was also confirmed by immunoblot analysis of caspase-3 processing and PARP cleavage. Pre-treatment of RCC and melanoma cell lines with FLLL32/62 did not inhibit IFN-γ-induced pSTAT1. In contrast to FLLL32, curcumin and FLLL62 reduced downstream STAT1-mediated gene expression of IRF1 as determined by Real Time PCR. FLLL32 and FLLL62 significantly reduced secretion of VEGF from RCC cell lines in a dose-dependent manner as determined by ELISA. Finally, each of these compounds inhibited in vitro generation of myeloid-derived suppressor cells. These data support further investigation of FLLL32 and FLLL62 as lead compounds for STAT3 inhibition in RCC and melanoma. PMID:22899991

  8. Anti-inflammatory and antioxidant effects of curcumin on acute lung injury in a rodent model of intestinal ischemia reperfusion by inhibiting the pathway of NF-Kb

    PubMed Central

    Fan, Zhe; Yao, Jihong; Li, Yang; Hu, Xiaowei; Shao, Huizhu; Tian, Xiaofeng

    2015-01-01

    Objective: To investigate the anti-inflammatory and antioxidant effect of curcumin on lung lesion induced by intestinal ischemia reperfusion injury (IIR). Methods: Rats were divided into four groups: sham, intestinal IIR (IIR), 1 mg/kg of curcumin treatment group (1 mg/kg), and 5 mg/kg of curcumin treatment group (5 mg/kg). Curcumin was given respectively (1 mg/kg and 5 mg/kg) following the above doses. IIR was produced by 1 h of intestinal ischemia followed by 2 h of reperfusion. Rats were sacrificed at the end of reperfusion and lung tissues were collected for biochemical and histopathological examination in 4 groups. Lung tissues histology and bronchoalveolar lavage fluid (BALF) protein were assayed. Serum IL-6, lung superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The expression level of NF-κB and ICAM-1 (including immunohistochemical analysis and western blot analysis) were also measured. Results: Lung tissue injury induced by IIR was obviously observed through pathology and BALF protein. MPO activity, IL-6 level and ICAM-1 expression were significantly increased with the elevation of NF-κB, simultaneously, SOD activity was decreased. With Treatment of curcumin, pathology and BALF protein of lung tissue were improved clearly. Inflammatory indexes (MPO activity, IL-6 level and ICAM-1) were improved and antioxidant index (SOD activity) was enhanced paralleled with NF-κB. Conclusion: Using curcumin effectively prevented IIR-induced lung injury. Anti-inflammatory and antioxidant effects of curcumin could be observed by inhibiting the pathway of NF-κB. PMID:26097529

  9. Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

    PubMed Central

    Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

    2015-01-01

    Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. PMID:26316750

  10. Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer

    NASA Astrophysics Data System (ADS)

    Zhang, Yumin; Yang, Cuihong; Wang, Weiwei; Liu, Jinjian; Liu, Qiang; Huang, Fan; Chu, Liping; Gao, Honglin; Li, Chen; Kong, Deling; Liu, Qian; Liu, Jianfeng

    2016-02-01

    Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff’s base reaction. The obtained prodrug conjugate could self-assemble in water at pH 7.4 into nanoparticles (PEG-DOX NPs) and encapsulate Cur into the core through hydrophobic interaction (PEG-DOX-Cur NPs). When the PEG-DOX-Cur NPs are internalized by tumor cells, the Schiff’s base linker between PEG and DOX would break in the acidic environment that is often observed in tumors, causing disassembling of the PEG-DOX-Cur NPs and releasing both DOX and Cur into the nuclei and cytoplasma of the tumor cells, respectively. Compared with free DOX, free Cur, free DOX-Cur combination, or PEG-DOX NPs, PEG-DOX-Cur NPs exhibited higher anti-tumor activity in vitro. In addition, the PEG-DOX-Cur NPs also showed prolonged blood circulation time, elevated local drug accumulation and increased tumor penetration. Enhanced anti-tumor activity was also observed from the PEG-DOX-Cur-treated animals, demonstrating better tumor inhibitory property of the NPs. Thus, the PEG-DOX-Cur prodrug nanoparticle system provides a simple yet efficient approach of drug delivery for chemotherapy.

  11. Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer

    PubMed Central

    Zhang, Yumin; Yang, Cuihong; Wang, Weiwei; Liu, Jinjian; Liu, Qiang; Huang, Fan; Chu, Liping; Gao, Honglin; Li, Chen; Kong, Deling; Liu, Qian; Liu, Jianfeng

    2016-01-01

    Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff’s base reaction. The obtained prodrug conjugate could self-assemble in water at pH 7.4 into nanoparticles (PEG-DOX NPs) and encapsulate Cur into the core through hydrophobic interaction (PEG-DOX-Cur NPs). When the PEG-DOX-Cur NPs are internalized by tumor cells, the Schiff’s base linker between PEG and DOX would break in the acidic environment that is often observed in tumors, causing disassembling of the PEG-DOX-Cur NPs and releasing both DOX and Cur into the nuclei and cytoplasma of the tumor cells, respectively. Compared with free DOX, free Cur, free DOX-Cur combination, or PEG-DOX NPs, PEG-DOX-Cur NPs exhibited higher anti-tumor activity in vitro. In addition, the PEG-DOX-Cur NPs also showed prolonged blood circulation time, elevated local drug accumulation and increased tumor penetration. Enhanced anti-tumor activity was also observed from the PEG-DOX-Cur-treated animals, demonstrating better tumor inhibitory property of the NPs. Thus, the PEG-DOX-Cur prodrug nanoparticle system provides a simple yet efficient approach of drug delivery for chemotherapy. PMID:26876480

  12. Core-shell microcapsules of solid lipid nanoparticles and mesoporous silica for enhanced oral delivery of curcumin.

    PubMed

    Kim, Sanghoon; Diab, Roudayna; Joubert, Olivier; Canilho, Nadia; Pasc, Andreea

    2016-04-01

    Newly designed microcapsules (MC) combining a core of solid lipid nanoparticle (SLN) and a mesoporous silica shell have been developed and explored as oral delivery system of curcumin (CU). CU-loaded MC (MC-CU) are 2μm sized and have a mesoporous silica shell of 0.3μm thickness with a wormlike structure as characterized by small angle X-ray scattering (SAXS), nitrogen adsorption/desorption and transmission electron microscopy (TEM) measurements. It was found that SLN acts as reservoir of curcumin while the mesoporous shell insures the protection and the controlled release of the drug. MC-CU displayed a pH-dependent in vitro release profile with marked drug retention at pH 2.8. Neutral red uptake assay together with confocal laser scanning microscopy (CLSM) showed a good cell tolerance to MC-CU at relatively high concentration of inert materials. Besides, the cell-uptake test revealed that fluorescent-MC were well internalized into Caco-2 cells, confirming the possibility to use MC for gut cells targeting. These findings suggest that organic core-silica shell microcapsules are promising drug delivery systems with enhanced bioavailability for poorly soluble drugs. PMID:26752213

  13. Gold Nanoparticles Inhibit Matrix Metalloproteases without Cytotoxicity.

    PubMed

    Hashimoto, M; Sasaki, J I; Yamaguchi, S; Kawai, K; Kawakami, H; Iwasaki, Y; Imazato, S

    2015-08-01

    Nanoparticles (NPs) are currently the focus of considerable attention for dental applications; however, their biological effects have not been fully elucidated. The long-term, slow release of matrix metalloproteases (MMPs) digests collagen fibrils within resin-dentin bonds. Therefore, MMP inhibitors can prolong the durability of resin-dentin bonds. However, there have been few reports evaluating the combined effect of MMP inhibition and the cytotoxic effects of NPs for dentin bonding. The aim of this study was to evaluate MMP inhibition and cytotoxic responses to gold (AuNPs) and platinum nanoparticles (PtNPs) stabilized by polyvinylpyrrolidone (PVP) in cultured murine macrophages (RAW264) by using MMP inhibition assays, measuring cell viability and inflammatory responses (quantitative reverse transcription polymerase chain reaction [RT-qPCR]), and conducting a micromorphological analysis by fluorescence and transmission electron microscopy. Cultured RAW264 cells were exposed to metal NPs at various concentrations (1, 10, 100, and 400 µg/mL). AuNPs and PtNPs markedly inhibited MMP-8 and MMP-9 activity. Although PtNPs were cytotoxic at high concentrations (100 and 400 µg/mL), no cytotoxic effects were observed for AuNPs at any concentration. Transmission electron microscopy images showed a significant nonrandom intercellular distribution for AuNPs and PtNPs, which were mostly observed to be localized in lysosomes but not in the nucleus. RT-qPCR analysis demonstrated inflammatory responses were not induced in RAW264 cells by AuNPs or PtNPs. The cytotoxicity of nanoparticles might depend on the core metal composition and arise from a "Trojan horse" effect; thus, MMP inhibition could be attributed to the surface charge of PVP, which forms the outer coating of NPs. The negative charge of the surface coating of PVP binds to Zn(2+) from the active center of MMPs by chelate binding and results in MMP inhibition. In summary, AuNPs are attractive NPs that effectively

  14. Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

    PubMed Central

    Santos, António M.; Lopes, Teresa; Oleastro, Mónica; Gato, Inês Vale; Floch, Pauline; Benejat, Lucie; Chaves, Paula; Pereira, Teresa; Seixas, Elsa; Machado, Jorge; Guerreiro, António S.

    2015-01-01

    Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available. PMID:25569625

  15. Curcumin inhibits gastric inflammation induced by Helicobacter pylori infection in a mouse model.

    PubMed

    Santos, António M; Lopes, Teresa; Oleastro, Mónica; Gato, Inês Vale; Floch, Pauline; Benejat, Lucie; Chaves, Paula; Pereira, Teresa; Seixas, Elsa; Machado, Jorge; Guerreiro, António S

    2015-01-01

    Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available. PMID:25569625

  16. Inhibition of cardiac oxidative and endoplasmic reticulum stress-mediated apoptosis by curcumin treatment contributes to protection against acute myocarditis.

    PubMed

    Mito, Sayaka; Thandavarayan, Rajarajan A; Ma, Meilei; Lakshmanan, Arunprasath; Suzuki, Kenji; Kodama, Makoto; Watanabe, Kenichi

    2011-10-01

    Curcumin is used anecdotally as an herb in traditional Indian and Chinese medicine. In the present study, the effects and possible mechanism of curcumin in experimental autoimmune myocarditis (EAM) rats were further investigated. They were divided randomly into a treatment and vehicle group, and orally administrated curcumin (50 mg/kg/day) and 1% gum arabic, respectively, for 3 weeks after myosin injection. The results showed that curcumin significantly suppressed the myocardial protein expression of inducible nitric oxide synthase (iNOS) and the catalytic subunit of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase. In addition, curcumin significantly decreased myocardial endoplasmic reticulum (ER) stress signaling proteins and improved cardiac function. Furthermore, curcumin significantly decreased the key regulators or inducers of apoptosis. In summary, our results indicate that curcumin has the potential to protect EAM by modulating cardiac oxidative and ER stress-mediated apoptosis, and provides a novel therapeutic strategy for autoimmune myocarditis. PMID:21781008

  17. Dimethoxy Curcumin Induces Apoptosis by Suppressing Survivin and Inhibits Invasion by Enhancing E-Cadherin in Colon Cancer Cells.

    PubMed

    Chen, Dong; Dai, Fang; Chen, Zhehang; Wang, Saisai; Cheng, Xiaobin; Sheng, Qinsong; Lin, Jianjiang; Chen, Wenbin

    2016-01-01

    BACKGROUND Dimethoxy curcumin (DMC) is a kind of lipophilic analog of curcumin with great improvement in chemical and metabolic stability. DMC has been studied in breast and renal cancer, but no research in colon cancer has been found yet. MATERIAL AND METHODS Two colon cancer cells (HT-29 and SW480) and one normal human colon mucosal epithelial cell (NCM460) were used in this study. We studied the effect of DMC on the proliferation in vitro and in vivo. Transwell migration assay was used to estimate the inhibition of DMC on invasion. Moreover, the expressions of PARP, caspase-3, survivin and E-cadherin were detected to uncover the related signaling pathways by western blotting assay both in vitro and in vivo. RESULTS DMC significantly inhibited the growth of colon cancer cells in dose-dependent manner; IC50 for DMC was calculated to be 43.4, 28.2 and 454.8µM on HT-29, SW480 and NCM460. DMC significantly increased the apoptosis in both HT-29 (p=0.0051) and SW480 (p=0.0013) cells in vitro, and significantly suppressed the growth of both cell lines in vivo. Moreover, DMC reduced the number of migrated cells in both HT-29 (p=0.007) and SW480 (p=0.004) cells. By western blotting analysis, the cleavage of pro-caspases-3 and PARP were clearly induced by DMC to their active form, while the expression of survivin was reduced and E-cadherin was enhanced in both cells in vitro and in vivo. CONCLUSIONS DMC may exert an effective anti-tumor effect in colon cancer cells by down-regulating survivin and upregulating E-cadherin. PMID:27614381

  18. Curcumin in inflammatory diseases.

    PubMed

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. PMID:23281076

  19. Interaction of metallic clusters with biologically active curcumin molecules

    NASA Astrophysics Data System (ADS)

    Gupta, Sanjeev K.; He, Haiying; Liu, Chunhui; Dutta, Ranu; Pandey, Ravindra

    2015-09-01

    We have investigated the interaction of subnano metallic Gd and Au clusters with curcumin, an important biomolecule having pharmacological activity. Gd clusters show different site preference to curcumin and much stronger interaction strength, in support of the successful synthesis of highly stable curcumin-coated Gd nanoparticles as reported recently. It can be attributed to significant charge transfer from the Gd cluster to curcumin together with a relatively strong hybridization of the Gd df-orbitals with curcumin p-orbitals. These results suggest that Gd nanoparticles can effectively be used as delivery carriers for curcumin at the cellular level for therapy and medical imaging applications.

  20. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis.

    PubMed

    Jain, S K; Gill, M S; Pawar, H S; Suresh, Sarasija

    2014-09-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01) alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin. PMID:25425755

  1. Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway.

    PubMed

    Mun, Se Hwan; Kim, Hyuk Soon; Kim, Jie Wan; Ko, Na Young; Kim, Do Kyun; Lee, Beob Yi; Kim, Bokyung; Won, Hyung Sik; Shin, Hwa-Sup; Han, Jeung-Whan; Lee, Hoi Young; Kim, Young Mi; Choi, Wahn Soo

    2009-09-01

    We investigated whether oral administration of curcumin suppressed type II collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway. PMID:19763044

  2. Inhibition of Autophagy Enhances Curcumin United light irradiation-induced Oxidative Stress and Tumor Growth Suppression in Human Melanoma Cells.

    PubMed

    Niu, Tianhui; Tian, Yan; Mei, Zhusong; Guo, Guangjin

    2016-01-01

    Malignant melanoma is the most aggressive form of skin carcinoma, which possesses fast propagating and highly invasive characteristics. Curcumin is a natural phenol compound that has various biological activities, such as anti-proliferative and apoptosis-accelerating impacts on tumor cells. Unfortunately, the therapeutical activities of Cur are severely hindered due to its extremely low bioavailability. In this study, a cooperative therapy of low concentration Cur combined with red united blue light irradiation was performed to inspect the synergistic effects on the apoptosis, proliferation and autophagy in human melanoma A375 cell. The results showed that red united blue light irradiation efficaciously synergized with Cur to trigger oxidative stress-mediated cell death, induce apoptosis and inhibit cell proliferation. Meanwhile, Western blotting revealed that combined disposure induced the formation of autophagosomes. Conversely, inhibition of the autophagy enhanced apoptosis, obstructed cell cycle arrest and induced reversible proliferation arrest to senescence. These findings suggest that Cur combined with red united blue light irradiation could generate photochemo-preventive effects via enhancing apoptosis and triggering autophagy, and pharmacological inhibition of autophagy convert reversible arrested cells to senescence, therefore reducing the possibility that damaged cells might escape programmed death. PMID:27502897

  3. Inhibition of Autophagy Enhances Curcumin United light irradiation-induced Oxidative Stress and Tumor Growth Suppression in Human Melanoma Cells

    PubMed Central

    Niu, Tianhui; Tian, Yan; Mei, Zhusong; Guo, Guangjin

    2016-01-01

    Malignant melanoma is the most aggressive form of skin carcinoma, which possesses fast propagating and highly invasive characteristics. Curcumin is a natural phenol compound that has various biological activities, such as anti-proliferative and apoptosis-accelerating impacts on tumor cells. Unfortunately, the therapeutical activities of Cur are severely hindered due to its extremely low bioavailability. In this study, a cooperative therapy of low concentration Cur combined with red united blue light irradiation was performed to inspect the synergistic effects on the apoptosis, proliferation and autophagy in human melanoma A375 cell. The results showed that red united blue light irradiation efficaciously synergized with Cur to trigger oxidative stress-mediated cell death, induce apoptosis and inhibit cell proliferation. Meanwhile, Western blotting revealed that combined disposure induced the formation of autophagosomes. Conversely, inhibition of the autophagy enhanced apoptosis, obstructed cell cycle arrest and induced reversible proliferation arrest to senescence. These findings suggest that Cur combined with red united blue light irradiation could generate photochemo-preventive effects via enhancing apoptosis and triggering autophagy, and pharmacological inhibition of autophagy convert reversible arrested cells to senescence, therefore reducing the possibility that damaged cells might escape programmed death. PMID:27502897

  4. Curcumin inhibits tumor epithelial‑mesenchymal transition by downregulating the Wnt signaling pathway and upregulating NKD2 expression in colon cancer cells.

    PubMed

    Zhang, Zewei; Chen, Haitao; Xu, Chao; Song, Lu; Huang, Lulu; Lai, Yuebiao; Wang, Yuqi; Chen, Hanlu; Gu, Danlin; Ren, Lili; Yao, Qinghua

    2016-05-01

    Tumor invasion and metastasis are closely associated with epithelial‑mesenchymal transition (EMT). EMT refers to epithelial cells under physiological and pathological conditions that are specific to mesenchymal transition. Curcumin inhibits EMT progression via Wnt signaling. The Wnt signaling pathway is a conservative EMT‑related signaling pathway that is involved in the development of various tumors. In the present study, MTS assays were employed to analyze the proliferation of curcumin‑treated cells. Naked cuticle homolog 2 (NKD2), chemokine receptor 4 (CXCR4) and antibodies associated with EMT were examined in SW620 colorectal cancer cell lines using western blot analysis and real‑time qPCR. NKD2 small‑interfering RNA (siRNA) and CXCR4 expression plasmid was synthesized and transfected into the colorectal cancer cell lines, and NKD2 and CXCR4 expression levels were detected. The results showed that curcumin significantly inhibited the proliferation of colorectal cancer cells and upregulated the expression of NKD2 in SW620 colorectal cancer cells and in the xenograft, resulting in the downregulation of key markers in the Wnt signaling. In addition, the progression of ETM was inhibited due to the overexpression of E‑cadherin as well as the downregulation of vimentin. Curcumin also inhibited tumor metastasis by downregulating the expression of CXCR4 significantly. The results suggested involvement of the NKD2‑Wnt‑CXCR4 signaling pathway in colorectal cancer cells. In addition, curcumin is inhibit this signaling and the development of colorectal cancer. PMID:26985708

  5. Development of curcumin nanocrystal: physical aspects.

    PubMed

    Rachmawati, Heni; Al Shaal, Loaye; Müller, Rainer H; Keck, Cornelia M

    2013-01-01

    Curcumin, a naturally occuring polyphenolic phytoconstituent, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). It is water insoluble under acidic or neutral conditions but dissolves in alkaline environment. In neutral or alkaline conditions, curcumin is highly unstable undergoing rapid hydrolytic degradation to feruloyl methane and ferulic acid. Thus, the use of curcumin is limited by its poor aqueous solubility in acidic or neutral conditions and instability in alkaline pH. In the present study, curcumin nanocrystals were prepared using high-pressure homogenization, to improve its solubility. Five different stabilizers [polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), sodium dodecyl sulfate (SDS), carboxymethylcellulose sodium salt] possessing different stabilization mechanism were investigated. The nanoparticles were characterized with regard to size, surface charge, shape and morphology, thermal property, and crystallinity. A short-term stability study was performed storing the differently stabilized nanoparticles at 4°C and room temperature. PVA, PVP, TPGS, and SDS successfully produced curcumin nanoparticle with the particle size in the range of 500-700 nm. PVA, PVP, and TPGS showed similar performance in preserving the curcumin nanosuspension stability. However, PVP is the most efficient polymer to stabilize curcumin nanoparticle. This study illustrates that the developed curcumin nanoparticle held great potential as a possible approach to improve the curcumin solubility then enhancing bioavailability. PMID:23047816

  6. Thermally responsive nanoparticle-encapsulated curcumin and its combination with mild hyperthermia for enhanced cancer cell destruction.

    PubMed

    Rao, Wei; Zhang, Wujie; Poventud-Fuentes, Izmarie; Wang, Yongchen; Lei, Yifeng; Agarwal, Pranay; Weekes, Benjamin; Li, Chenglong; Lu, Xiongbin; Yu, Jianhua; He, Xiaoming

    2014-02-01

    In this study, thermally responsive polymeric nanoparticle-encapsulated curcumin (nCCM) was prepared and characterized. The nCCM is ≈ 22 and 300 nm in diameter at 37 and 22 °C, respectively. The smaller size of the nCCM at 37 °C was found to significantly facilitate its uptake in vitro by human prostate adenocarcinoma PC-3 cancer cells. However, the intracellular nCCM decreases rapidly (rather than plateaus) after reaching its peak at ≈ 1.5 h during a 3-day incubation of the PC-3 cells with nCCM. Moreover, a mild hyperthermia (with negligible cytotoxicity alone) at 43 °C applied between 1 and 1.5 h during the 3-day incubation not only increases the peak uptake but also alters intracellular distribution of nCCM (facilitating its delivery into cell nuclei), which helps to retain a significantly much higher level of intracellular curcumin. These effects of mild hyperthermia could be due in part to the thermal responsiveness of the nCCM: they are more positively charged at 43 °C and can be more easily attracted to the negatively charged nuclear membrane to enter nuclei as a result of electrostatic interaction. Ultimately, a combination of the thermally responsive nCCM and mild hyperthermia significantly enhances the anticancer capability of nCCM, resulting in a more than 7-fold decrease in its inhibitory concentration to reduce cell viability to 50% (IC50). Further mechanistic studies suggest injury pathways associated with heat shock proteins 27 and 70 should contribute to the enhanced cancer cell destruction by inducing cell apoptosis and necrosis. Overall, this study demonstrates the potential of combining mild hyperthermia and thermally responsive nanodrugs such as nCCM for augmented cancer therapy. PMID:24516867

  7. Thermally Responsive Nanoparticle-Encapsulated Curcumin and Its Combination with Mild Hyperthermia for Enhanced Cancer Cell Destruction.

    PubMed

    Rao, Wei; Zhang, Wujie; Poventud-Fuentes, Izmarie; Wang, Yongchen; Lei, Yifeng; Agarwal, Pranay; Weekes, Benjamin; Li, Chenglong; Lu, Xiongbin; Yu, Jianhua; He, Xiaoming

    2013-10-26

    In this study, thermally responsive polymeric nanoparticle-encapsulated curcumin (nCCM) was prepared and characterized. The nCCM is ∼ 22 and 300 nm in diameter at 37 and 22 °C, respectively. The smaller size of the nCCM at 37 °C was found to significantly facilitate its uptake in vitro by human prostate adenocarcinoma PC-3 cancer cells. However, the intracellular nCCM decreases rapidly (rather than plateaus) after reaching its peak at ∼ 1.5 h during a 3-day incubation of the PC-3 cells with nCCM. Moreover, a mild hyperthermia (with negligible cytotoxicity alone) at 43 °C applied between 1 and 1.5 h during the 3-day incubation not only increases the peak uptake but also alters intracellular distribution of nCCM (facilitating its delivery into cell nuclei), which helps to retain a significantly much higher level of intracellular curcumin. These effects of the mild hyperthermia could be due in part to the thermal responsiveness of the nCCM: they are more positively charged at 43 °C and can be more easily attracted to the negatively charged nuclear membrane to enter nuclei as a result of electrostatic interaction. Ultimately, a combination of the thermally responsive nCCM and mild hyperthermia significantly enhances the anticancer capability of nCCM, resulting in a decrease of more than 7 times in its inhibitory concentration to reduce cell viability to 50% (IC50). Further mechanistic studies suggest injury pathways associated with heat shock protein (HSP) 27 and 70 should contribute to the enhanced cancer cell destruction by inducing cell apoptosis and necrosis. Taken together, this study demonstrates the potential of combining mild hyperthermia and thermally responsive nanodrugs such as nCCM for augmented cancer therapy. PMID:24513412

  8. Nanocomplexation between curcumin and soy protein isolate: influence on curcumin stability/bioaccessibility and in vitro protein digestibility.

    PubMed

    Chen, Fei-Ping; Li, Bian-Sheng; Tang, Chuan-He

    2015-04-01

    The complexation of nanoparticles in unheated and heated (at 75-95°) soy protein isolate (SPI) with curcumin and the effects on curcumin stability/bioaccessibility and in vitro protein digestibility were investigated. The nanoparticles did not display noticeable changes in size and morphology upon nanocomplexation with curcumin, except their surface hydrophobicity. The encapsulation efficiency of curcumin progressively decreased with increasing initial curcumin concentration in the dispersion, while the load amount linearly increased. The solubility of curcumin in water was enhanced by the complexation above 98000-fold (vs free curcumin in water). The formation of the nanocomplexes considerably improved the storage stability of curcumin. In vitro simulated digestion experiments indicated that the complexation also improved the bioaccessibility of curcumin; the bioaccessibility was greatly impaired by hydrolysis-induced protein aggregation. Addtionally, the nanocomplexation significantly improved the in vitro protein digestibility of both unheated and heated SPI. PMID:25779681

  9. Curcumin suppresses NTHi-induced CXCL5 expression via inhibition of positive IKKβ pathway and up-regulation of negative MKP-1 pathway.

    PubMed

    Konduru, Anuhya S; Lee, Byung-Cheol; Li, Jian-Dong

    2016-01-01

    Otitis media (OM) is the most common childhood bacterial infection, and leading cause of conductive hearing loss. Nontypeable Haemophilus influenzae (NTHi) is a major bacterial pathogen for OM. OM characterized by the presence of overactive inflammatory responses is due to the aberrant production of inflammatory mediators including C-X-C motif chemokine ligand 5 (CXCL5). The molecular mechanism underlying induction of CXCL5 by NTHi is unknown. Here we show that NTHi up-regulates CXCL5 expression by activating IKKβ-IκBα and p38 MAPK pathways via NF-κB nuclear translocation-dependent and -independent mechanism in middle ear epithelial cells. Current therapies for OM are ineffective due to the emergence of antibiotic-resistant NTHi strains and risk of side effects with prolonged use of immunosuppressant drugs. In this study, we show that curcumin, derived from Curcuma longa plant, long known for its medicinal properties, inhibited NTHi-induced CXCL5 expression in vitro and in vivo. Curcumin suppressed CXCL5 expression by direct inhibition of IKKβ phosphorylation, and inhibition of p38 MAPK via induction of negative regulator MKP-1. Thus, identification of curcumin as a potential therapeutic for treating OM is of particular translational significance due to the attractiveness of targeting overactive inflammation without significant adverse effects. PMID:27538525

  10. Curcumin suppresses NTHi-induced CXCL5 expression via inhibition of positive IKKβ pathway and up-regulation of negative MKP-1 pathway

    PubMed Central

    Konduru, Anuhya S.; Lee, Byung-Cheol; Li, Jian-Dong

    2016-01-01

    Otitis media (OM) is the most common childhood bacterial infection, and leading cause of conductive hearing loss. Nontypeable Haemophilus influenzae (NTHi) is a major bacterial pathogen for OM. OM characterized by the presence of overactive inflammatory responses is due to the aberrant production of inflammatory mediators including C-X-C motif chemokine ligand 5 (CXCL5). The molecular mechanism underlying induction of CXCL5 by NTHi is unknown. Here we show that NTHi up-regulates CXCL5 expression by activating IKKβ-IκBα and p38 MAPK pathways via NF-κB nuclear translocation-dependent and -independent mechanism in middle ear epithelial cells. Current therapies for OM are ineffective due to the emergence of antibiotic-resistant NTHi strains and risk of side effects with prolonged use of immunosuppressant drugs. In this study, we show that curcumin, derived from Curcuma longa plant, long known for its medicinal properties, inhibited NTHi-induced CXCL5 expression in vitro and in vivo. Curcumin suppressed CXCL5 expression by direct inhibition of IKKβ phosphorylation, and inhibition of p38 MAPK via induction of negative regulator MKP-1. Thus, identification of curcumin as a potential therapeutic for treating OM is of particular translational significance due to the attractiveness of targeting overactive inflammation without significant adverse effects. PMID:27538525

  11. A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition.

    PubMed

    Song, Ju-Xian; Sun, Yue-Ru; Peluso, Ivana; Zeng, Yu; Yu, Xing; Lu, Jia-Hong; Xu, Zheng; Wang, Ming-Zhong; Liu, Liang-Feng; Huang, Ying-Yu; Chen, Lei-Lei; Durairajan, Siva Sundara Kumar; Zhang, Hong-Jie; Zhou, Bo; Zhang, Hong-Qi; Lu, Aiping; Ballabio, Andrea; Medina, Diego L; Guo, Zhihong; Li, Min

    2016-08-01

    Autophagy dysfunction is a common feature in neurodegenerative disorders characterized by accumulation of toxic protein aggregates. Increasing evidence has demonstrated that activation of TFEB (transcription factor EB), a master regulator of autophagy and lysosomal biogenesis, can ameliorate neurotoxicity and rescue neurodegeneration in animal models. Currently known TFEB activators are mainly inhibitors of MTOR (mechanistic target of rapamycin [serine/threonine kinase]), which, as a master regulator of cell growth and metabolism, is involved in a wide range of biological functions. Thus, the identification of TFEB modulators acting without inhibiting the MTOR pathway would be preferred and probably less deleterious to cells. In this study, a synthesized curcumin derivative termed C1 is identified as a novel MTOR-independent activator of TFEB. Compound C1 specifically binds to TFEB at the N terminus and promotes TFEB nuclear translocation without inhibiting MTOR activity. By activating TFEB, C1 enhances autophagy and lysosome biogenesis in vitro and in vivo. Collectively, compound C1 is an orally effective activator of TFEB and is a potential therapeutic agent for the treatment of neurodegenerative diseases. PMID:27172265

  12. Curcumin is an in vivo inhibitor of angiogenesis.

    PubMed Central

    Arbiser, J. L.; Klauber, N.; Rohan, R.; van Leeuwen, R.; Huang, M. T.; Fisher, C.; Flynn, E.; Byers, H. R.

    1998-01-01

    BACKGROUND: Curcumin is a small-molecular-weight compound that is isolated from the commonly used spice turmeric. In animal models, curcumin and its derivatives have been shown to inhibit the progression of chemically induced colon and skin cancers. The genetic changes in carcinogenesis in these organs involve different genes, but curcumin is effective in preventing carcinogenesis in both organs. A possible explanation for this finding is that curcumin may inhibit angiogenesis. MATERIALS AND METHODS: Curcumin was tested for its ability to inhibit the proliferation of primary endothelial cells in the presence and absence of basic fibroblast growth factor (bFGF), as well as its ability to inhibit proliferation of an immortalized endothelial cell line. Curcumin and its derivatives were subsequently tested for their ability to inhibit bFGF-induced corneal neovascularization in the mouse cornea. Finally, curcumin was tested for its ability to inhibit phorbol ester-stimulated vascular endothelial growth factor (VEGF) mRNA production. RESULTS: Curcumin effectively inhibited endothelial cell proliferation in a dose-dependent manner. Curcumin and its derivatives demonstrated significant inhibition of bFGF-mediated corneal neovascularization in the mouse. Curcumin had no effect on phorbol ester-stimulated VEGF production. CONCLUSIONS: These results indicate that curcumin has direct antiangiogenic activity in vitro and in vivo. The activity of curcumin in inhibiting carcinogenesis in diverse organs such as the skin and colon may be mediated in part through angiogenesis inhibition. Images Fig. 2 PMID:10780880

  13. Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation.

    PubMed

    Clutterbuck, Abigail L; Mobasheri, Ali; Shakibaei, Mehdi; Allaway, David; Harris, Pat

    2009-08-01

    Osteoarthritis (OA) is a degenerative and inflammatory disease of synovial joints that is characterized by the loss of articular cartilage, for which there is increasing interest in natural remedies. Curcumin (diferuloylmethane) is the main polyphenol in the spice turmeric, derived from rhizomes of the plant Curcuma longa. Curcumin has potent chemopreventive properties and has been shown to inhibit nuclear factor kappaB-mediated inflammatory signaling in many cell types, including chondrocytes. In this study, normal articular cartilage was harvested from metacarpophalangeal and metatarsophalangeal joints of eight horses, euthanized for reasons other than research purposes, to establish an explant model mimicking the inflammatory events that occur in OA. Initially, cartilage explants (N= 8) were stimulated with increasing concentrations of the proinflammatory cytokine IL-1beta to select effective doses for inducing cartilage degeneration in the explant model. Separate cartilage explants were then cotreated with IL-1beta at either 10 ng/mL (n= 3) or 25 ng/mL (n= 3) and curcumin (0.1 micromol/L, 0.5 micromol/L, 1 micromol/L, 10 micromol/L, and 100 micromol/L). After 5 days, the percentage of glycosaminoglycan (GAG) release from the explants was assessed using a dimethylmethylene blue colorimetric assay. Curcumin (100 micromol/L) significantly reduced IL-1beta-stimulated GAG release in the explants by an average of 20% at 10 ng/mL and 27% at 25 ng/mL back to unstimulated control levels (P < 0.001). Our results suggest that this explant model effectively simulates the proinflammatory cytokine-mediated release of articular cartilage components seen in OA. Furthermore, the evidence suggests that the inflammatory cartilage explant model is useful for studying the effects of curcumin on inflammatory pathways and gene expression in IL-1beta-stimulated chondrocytes. PMID:19723086

  14. Plant-derived anticancer agents - curcumin in cancer prevention and treatment.

    PubMed

    Creţu, Elena; Trifan, Adriana; Vasincu, Al; Miron, Anca

    2012-01-01

    Nowadays cancer is still a major public health issue. Despite all the progresses made in cancer prevention, diagnosis and treatment, mortality by cancer is on the second place after the one caused by cardiovascular diseases. The high mortality and the increasing incidence of certain cancers (lung, prostate, colorectal) justify a growing interest for the identification of new pharmacological agents efficient in cancer prevention and treatment. In the last fifty years many plant-derived agents (vinblastine, vincristine, vindesine, paclitaxel, docetaxel, topotecan, irinotecan, elliptinium) played a major role in cancer treatment. Other very promising plant-derived anticancer agents (combrestatins, betulinic acid, roscovitine, purvalanols, indirubins) are in clinical or preclinical trials. Curcumin, a liposoluble polyphenolic pigment isolated from the rhizomes of Curcuma longa L. (Zingiberaceae), is another potential candidate for new anticancer drug development. Curcumin has been reported to influence many cell-signaling pathways involved in tumor initiation and proliferation. Curcumin inhibits COX-2 activity, cyclin D1 and MMPs overexpresion, NF-kB, STAT and TNF-alpha signaling pathways and regulates the expression of p53 tumor suppressing gene. Curcumin is well-tolerated but has a reduced systemic bioavailability. Polycurcumins (PCurc 8) and curcumin encapsulated in biodegradable polymeric nanoparticles (NanoCurc) showed higher bioavailability than curcumin together with a significant tumor growth inhibition in both in vitro and in vivo studies. BILITY. PMID:23700916

  15. Analysis of the Antiproliferative Effects of Curcumin and Nanocurcumin in MDA-MB231 as a Breast Cancer Cell Line

    PubMed Central

    Khosropanah, Mohammad Hossein; Dinarvand, Amin; Nezhadhosseini, Afsaneh; Haghighi, Alireza; Hashemi, Sima; Nirouzad, Fereidon; Khatamsaz, Sepideh; Entezari, Maliheh; Hashemi, Mehrdad; Dehghani, Hossein

    2016-01-01

    Cancer is one of the main causes of mortality in the world which appears by the effect of enviromental physico-chemical mutagen and carcinogen agents. The identification of new cytotoxic drug with low sid effects on immune system has developed as important area in new studies of immunopharmacology. Curcumin is a natural polyphenol with anti-oxidative, anti-inflammatory and anti-cancer properties. Its therapeutic potential is substantially hindered by the rather low water solubility and bioavailability, hence the need for suitable carriers. In this report we employed nanogel-based nanoparticle approach to improve upon its effectiveness. Myristic acid-chitosan (MA-chitosan) nanogels were prepared by the technique of self-assembly. Curcumin was loaded into the nanogels. The surface morphology of the prepared nanoparticles was determined using SEM and TEM. The other objective of this study was to examine the in vitro cytotoxic activity of cell death of curcumin and nanocurcumin on human breast adenocarcinoma cell line (MDA-MB231). Cytotoxicity and viability of curcumin and nanocurcumin were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. Proliferation of MDA-MB231 cells was significantly inhibited by curcumin and nanocurcumin in a concentration-dependent manner in defined times. There were significant differences in IC50 curcumin and nanocurcumin. curcumin -loaded nanoparticles proved more effective compared to TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the anticancer properties of curcumin -loaded nanoparticles. PMID:27610163

  16. Analysis of the Antiproliferative Effects of Curcumin and Nanocurcumin in MDA-MB231 as a Breast Cancer Cell Line.

    PubMed

    Khosropanah, Mohammad Hossein; Dinarvand, Amin; Nezhadhosseini, Afsaneh; Haghighi, Alireza; Hashemi, Sima; Nirouzad, Fereidon; Khatamsaz, Sepideh; Entezari, Maliheh; Hashemi, Mehrdad; Dehghani, Hossein

    2016-01-01

    Cancer is one of the main causes of mortality in the world which appears by the effect of enviromental physico-chemical mutagen and carcinogen agents. The identification of new cytotoxic drug with low sid effects on immune system has developed as important area in new studies of immunopharmacology. Curcumin is a natural polyphenol with anti-oxidative, anti-inflammatory and anti-cancer properties. Its therapeutic potential is substantially hindered by the rather low water solubility and bioavailability, hence the need for suitable carriers. In this report we employed nanogel-based nanoparticle approach to improve upon its effectiveness. Myristic acid-chitosan (MA-chitosan) nanogels were prepared by the technique of self-assembly. Curcumin was loaded into the nanogels. The surface morphology of the prepared nanoparticles was determined using SEM and TEM. The other objective of this study was to examine the in vitro cytotoxic activity of cell death of curcumin and nanocurcumin on human breast adenocarcinoma cell line (MDA-MB231). Cytotoxicity and viability of curcumin and nanocurcumin were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. Proliferation of MDA-MB231 cells was significantly inhibited by curcumin and nanocurcumin in a concentration-dependent manner in defined times. There were significant differences in IC50 curcumin and nanocurcumin. curcumin -loaded nanoparticles proved more effective compared to TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the anticancer properties of curcumin -loaded nanoparticles. PMID:27610163

  17. Curcumin mediates reversion of HGF-induced epithelial-mesenchymal transition via inhibition of c-Met expression in DU145 cells

    PubMed Central

    HU, HUI-JUN; LIN, XIAO-LONG; LIU, MI-HUA; FAN, XIAO-JUAN; ZOU, WEI-WEN

    2016-01-01

    The hepatocyte growth factor (HGF)/c-Met signaling pathway results in cancer cell scattering and invasion, and has been reported to participate in several types of cancer, including prostate and colorectal cancer. The downstream phosphorylation cascade of HGF, particularly the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT signaling pathway, regulates epithelial-mesenchymal transition (EMT). However, the mechanism by which these signaling pathways govern EMT, and whether certain kinases are able to respond to specific EMT effectors, remains to be elucidated. In the present study, an increase in the levels of vimentin, rather than co-regulation of certain EMT marker proteins, was observed in response to HGF-induced EMT in DU145 prostate cancer cells. In addition, it was observed that curcumin abrogated HGF-induced DU145 cell scattering and invasion. Furthermore, curcumin was able to effectively inhibit the HGF-induced increase in the levels of vimentin by downregulating the expression of phosphorylated c-Met, extracellular signal-regulated kinase and Snail. In conclusion, the results of the present study demonstrated that curcumin was able to reverse HGF-induced EMT, possibly by inhibiting c-Met expression in DU145 prostate cancer cells. PMID:26893768

  18. Bioavailability of curcumin and curcumin glucuronide in the central nervous system of mice after oral delivery of nano-curcumin.

    PubMed

    Szymusiak, Magdalena; Hu, Xiaoyu; Leon Plata, Paola A; Ciupinski, Paulina; Wang, Zaijie Jim; Liu, Ying

    2016-09-10

    Curcumin is a bioactive molecule extracted from Turmeric roots that has been recognized to possess a wide variety of important biological activities. Despite its great pharmacological activities, curcumin is highly hydrophobic, which results in poor bioavailability. We have formulated this hydrophobic compound into stable polymeric nanoparticles (nano-curcumin) to enhance its oral absorption. Pharmacokinetic analysis after oral delivery of nano-curcumin in mice demonstrated approximately 20-fold reduction in dose requirement when compared to unformulated curcumin to achieve comparable plasma and central nervous system (CNS) tissue concentrations. This investigation corroborated our previous study of curcumin functionality of attenuating opioid tolerance and dependence, which shows equivalent efficacy of low-dose (20mg/kg) nano-curcumin and high-dose (400mg/kg) pure curcumin in mice. Furthermore, the highly selective and validated liquid chromatography-mass spectrometry (LC-MS) method was developed to quantify curcumin glucuronide, the major metabolite of curcumin. The results suggest that the presence of curcumin in the CNS is essential for prevention and reversal of opioid tolerance and dependence. PMID:27426105

  19. Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways.

    PubMed

    Bortel, Nicola; Armeanu-Ebinger, Sorin; Schmid, Evi; Kirchner, Bettina; Frank, Jan; Kocher, Alexa; Schiborr, Christina; Warmann, Steven; Fuchs, Jörg; Ellerkamp, Verena

    2015-12-01

    In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC. PMID:26515460

  20. Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways

    PubMed Central

    Bortel, Nicola; Armeanu-Ebinger, Sorin; Schmid, Evi; Kirchner, Bettina; Frank, Jan; Kocher, Alexa; Schiborr, Christina; Warmann, Steven; Fuchs, Jörg; Ellerkamp, Verena

    2015-01-01

    In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC. PMID:26515460

  1. Co-delivery of camptothecin and curcumin by cationic polymeric nanoparticles for synergistic colon cancer combination chemotherapy†

    PubMed Central

    Xiao, Bo; Si, Xiaoying; Han, Moon Kwon; Viennois, Emilie; Zhang, Mingzhen; Merlin, Didier

    2015-01-01

    Nanoparticle (NP)-based combination chemotherapy has been proposed as a potent strategy for enhancing intracellular drug concentrations and achieving synergistic effects in colon cancer therapy. Here, we fabricated a series of chitosan-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs with various weight ratios of CPT to CUR. The resultant cationic spherical CPT/CUR-NPs had a desirable particle size (193–224 nm), relatively narrow size distribution, and slightly positive zeta-potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the study period with a slight, initial burst release. Subsequent cellular uptake experiments demonstrated that the introduction of chitosan to the NP surface markedly increased cellular-uptake efficiency compared with other drug formulations, and thus increased the intracellular drug concentrations. Importantly, the combined delivery of CPT and CUR in a single NP enhanced synergistic effects of the two drugs. Among the five cationic CPT/CUR-NPs tested, NPs with a CPT/CUR weight ratio of 4:1 showed the highest anticancer activity, resulting in a combination index of approximately 0.46. In summary, our study represents the first report of combinational application of CPT and CUR with a one-step–fabricated co-delivery system for effective colon cancer combination chemotherapy. PMID:26617985

  2. Green colorimetric recognition of trace sulfide ions in water samples using curcumin nanoparticle in micelle mediated system.

    PubMed

    Pourreza, Nahid; Golmohammadi, Hamed

    2014-02-01

    In this paper, green curcumin nanoparticles (CURNs) are introduced for colorimetric sensing of sulfide using micelle mediated cloud point extraction for the first time. CURNs are transferred into non-ionic surfactant phase and show strong surface plasmon absorption intensity. The extraction of CURNs to the surfactant rich phase is suppressed in the presence of Cu(2+) but upon addition of sulfide, the extraction of CURNs to the surfactant rich phase is increased again. This increase in the absorbance of surfactant rich phase is related to the sulfide concentration and was used as an analytical signal for the sensing of sulfide. The effect of chemical variables such as pH of the sample solution, concentration of Cu(2+), electrolyte and CURNs on the cloud point extraction was studied. Under optimum conditions, the change in absorption intensity was linearly proportional to the concentration of sulfide in the range of 0.5-200.0 ng mL(-1) with a detection limit of 0.4 ng mL(-1). The relative standard deviations for 10 replicate measurements of 20 ng mL(-1) and 175 ng mL(-1) of sulfide were 4.1% and 1.4% respectively. The method was successfully applied to the determination of sulfide in different water samples. PMID:24401402

  3. Silver_ nanoparticles inhibited erythrogenesis during zebrafish embryogenesis.

    PubMed

    Cui, Bei; Ren, Long; Xu, Qin-Han; Yin, Li-Yan; Zhou, Xin-Ying; Liu, Jing-Xia

    2016-08-01

    Silver_ nanoparticles (AgNPs), for their attractive antimicrobial properties, have become one of the most commercial nanomaterials used recently. AgNPs are reported to be toxic to blood cells of aquatic organisms and humans, however, few studies related to toxic effects of AgNPs in hematopoiesis using an in vivo model were available. Firstly, microarrays were applied to reveal transcriptional responses of zebrafish embryos to AgNPs at 24h post-fertilization (hpf)in this study, and hemoglobin genes were found to be down-regulated by AgNPs and to be enriched in the top 10 categories by Gene Ontology (GO) analysis. The reduced expressions of hemoglobin were further demonstrated by qRT-PCR detection, whole-mount in situ hybridization, and O-dianisidine staining at transcriptional and translational level. Next, the commitment of mesoderm, specification of hematopoietic progenitor cells and differentiation of erythroids were detected at different developmental stages in AgNPs-exposed embryos, and erythrogenesis were found to be inhibited by AgNPs in developmental-stage-specific and cell-specific manners. Finally, it was pointed out that AgNPs affected erythrogenesis mostly by their particles other than their releasing ions. PMID:27340786

  4. Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.

    PubMed

    Jancinová, Viera; Perecko, Tomás; Nosál, Radomír; Kostálová, Daniela; Bauerová, Katarína; Drábiková, Katarína

    2009-06-10

    Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane. PMID:19371737

  5. A Curcumin Derivative That Inhibits Vinyl Carbamate-Induced Lung Carcinogenesis via Activation of the Nrf2 Protective Response

    PubMed Central

    Shen, Tao; Jiang, Tao; Long, Min; Chen, Jun; Ren, Dong-Mei; Wong, Pak Kin

    2015-01-01

    Abstract Aims: Lung cancer has a high worldwide morbidity and mortality. The employment of chemopreventive agents is effective to reduce lung cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) mitigates insults from both exogenous and endogenous sources and thus has been verified as a target for chemoprevention. Curcumin has long been recognized as a chemopreventive agent, but poor bioavailability and weak Nrf2 induction have prohibited clinical application. Thus, we have developed new curcumin derivatives and tested their Nrf2 induction. Results: Based on curcumin, we synthesized curcumin analogs with five carbon linkages and established a structure–activity relationship for Nrf2 induction. Among these derivatives, bis[2-hydroxybenzylidene]acetone (BHBA) was one of the most potent Nrf2 inducers with minimal toxicity and improved pharmacological properties and was thus selected for further investigation. BHBA activated the Nrf2 pathway in the canonical Keap1-Cys151-dependent manner. Furthermore, BHBA was able to protect human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. More importantly, in an in vivo vinyl carbamate-induced lung cancer model in A/J mice, preadministration of BHBA significantly reduced lung adenocarcinoma, while curcumin failed to show any effects even at high doses. Innovation: The curcumin derivative, BHBA, is a potent inducer of Nrf2. It was demonstrated to protect against As(III) toxicity in lung epithelial cells in an Nrf2-dependent manner. Furthermore, compared with curcumin, BHBA displayed improved chemopreventive activities in a carcinogen-induced lung cancer model. Conclusion: Taken together, our results demonstrate that BHBA, a curcumin analog with improved Nrf2-activating and chemopreventive activities both in vitro and in vivo, could be developed into a chemoprotective pharmacological agent. Antioxid. Redox Signal. 23, 651–664. PMID:25891177

  6. Effect of polymer architecture on curcumin encapsulation and release from PEGylated polymer nanoparticles: Toward a drug delivery nano-platform to the CNS.

    PubMed

    Rabanel, Jean-Michel; Faivre, Jimmy; Paka, Ghislain Djiokeng; Ramassamy, Charles; Hildgen, Patrice; Banquy, Xavier

    2015-10-01

    We developed a nanoparticles (NPs) library from poly(ethylene glycol)-poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a "micelle-like" or "polymer nano-aggregate" structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to "polymer nano-aggregate" particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers. PMID:26409200

  7. Curcumin suppresses invasiveness and vasculogenic mimicry of squamous cell carcinoma of the larynx through the inhibition of JAK-2/STAT-3 signaling pathway.

    PubMed

    Hu, An; Huang, Jing-Juan; Jin, Xiao-Jie; Li, Ji-Ping; Tang, Yuan-Jia; Huang, Xin-Fang; Cui, Hui-Juan; Xu, Wei-Hua; Sun, Guang-Bin

    2015-01-01

    To determine the role of JAK-2/STAT-3 signaling pathway in invasion and vasculogenic mimicry of laryngeal squamous cell carcinoma. HEp-2 cells were treated with 1 or 10 μmol/L curcumin and AG490 (the inhibitor of JAK-2) for 48 h, the invasion and vasculogenic mimicry of tumor cells were tested with Transwell chamber test and tube formation experiment. RT-PCR was used to measure the expression of MMP-2 and VEGF. Western blot assay was employed to determine the expression of JAK-2, STAT3, p-STAT3, MMP-2 and VEGF. Compared to control group,there were less tumor cells permeating membrane and less formed tubes after curcumin or AG490 treatment, RT-PCR showed that the expression of MMP-2 and VEGF at mRNA level were decreased (P < 0.01). Western blotting indicated that the expression of JAK-2, p-STAT3, MMP-2 and VEGF at protein levels were decreased (P < 0.01), while that of STAT-3 protein had no difference among each group (P > 0.05). Immunofluorescence staining demonstrated that the expression of eNOS was down-regulated (P < 0.01). Curcumin and AG490 significantly inhibits invasion and vasculogenic mimicry of laryngeal squamous cell carcinoma in vitro, and JAK-2/STAT-3 signaling pathway promotes above processes. PMID:25628937

  8. Perspectives on New Synthetic Curcumin Analogs and their Potential Anticancer Properties

    PubMed Central

    Vyas, Alok; Dandawate, Prasad; Padhye, Subhash; Ahmad, Aamir; Sarkar, Fazlul

    2013-01-01

    Curcumin is the active component of dried rhizome of Curcuma longa, a perennial herb belonging to ginger family, cultivated extensively in south and southeastern tropical Asia. It is widely consumed in the Indian subcontinent, south Asia and Japan in traditional food recipes. Extensive research over last few decades has shown that curcumin is a potent anti-inflammatory agent with powerful therapeutic potential against a variety of cancers. It suppresses proliferation and metastasis of human tumors through regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases and other enzymes. It induces apoptotic cell death and also inhibits proliferation of cancer cells by cell cycle arrest. Pharmacokinetic data has shown that curcumin undergoes rapid metabolism leading to glucuronidation and sulfation in the liver and excretion in the feces, which accounts for its poor systemic bioavailability. The compound has, therefore, been formulated and administered using different drug delivery systems such as liposomes, micelles, polysaccharides, phospholipid complexes and nanoparticles that can overcome the limitation of bioavailability to some extent. Attempts to avoid rapid metabolism of curcumin until now have been met with limited success. This has prompted researchers to look for new synthetic curcumin analogs in order to overcome the drawbacks of limited bioavailability and rapid metabolism, and gain efficacy with reduced toxicity. In this review we provide a summarized account of novel synthetic curcumin formulations and analogs, and the recent progress in the field of cancer prevention and treatment. PMID:23116312

  9. Curcumin Ameliorates Reserpine-Induced Gastrointestinal Mucosal Lesions Through Inhibiting IκB-α/NF-κB Pathway and Regulating Expression of Vasoactive Intestinal Peptide and Gastrin in Rats.

    PubMed

    Long, Lingli; Wang, Jingnan; Chen, Ningning; Zheng, Shuhui; Shi, Lanying; Xu, Yuxia; Luo, Canqiao; Deng, Yubin

    2016-06-01

    The objective of our study was to investigate whether curcumin protects against reserpine-induced gastrointestinal mucosal lesions (GMLs) in rats and to explore the mechanism of curcumin's action. Sprague-Dawley rats were randomly divided into four groups: control group, reserpine-treated group, reserpine treatment group with curcumin at high dose (200 mg/kg), and reserpine treatment group with curcumin at low dose (100 mg/kg). Rats in reserpine-treated group were induced by intraperitoneally administered reserpine (0.5 mg/kg) for 28 days. TUNEL staining and hematoxylin and eosin staining were used to evaluate the apoptotic cells and morphologic changes. In addition, to explore the mechanism of curcumin in protecting GMLs, we used serum of experimental rats to assess the level of vasoactive intestinal peptide (VIP), gastrin, interleukin-6, interleukin-10, tumor necrosis factor-α and interferon-γ by ELISA and radioimmunoassay. The protein levels of NF-κB, p-IκB-α, IκB-α, Bcl-2, Bax, and cleaved-caspase-3 were examined by western blot analysis. Data were analyzed with SPSS 19.0 software package. Curcumin treatment prevented tissue damage and cell death in the reserpine-treated rats and effectively decreased inflammatory response and balanced the expression of VIP and gastrin in the reserpine-treated rats. NF-κB, p-IκB-α, Bax, and cleaved-caspase-3 were increased in the reserpine group, but the curcumin high-dose group inhibited them. Curcumin can target the IκB-α/NF-κB pathway to inhibit inflammatory response and regulate the level of VIP and gastrin in reserpine-induced GML rats. PMID:26872103

  10. miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and -2.

    PubMed

    Kronski, Emanuel; Fiori, Micol E; Barbieri, Ottavia; Astigiano, Simonetta; Mirisola, Valentina; Killian, Peter H; Bruno, Antonino; Pagani, Arianna; Rovera, Francesca; Pfeffer, Ulrich; Sommerhoff, Christian P; Noonan, Douglas M; Nerlich, Andreas G; Fontana, Laura; Bachmeier, Beatrice E

    2014-05-01

    Chronic inflammation is a major risk factor for the development and metastatic progression of cancer. We have previously reported that the chemopreventive polyphenol Curcumin inhibits the expression of the proinflammatory cytokines CXCL1 and -2 leading to diminished formation of breast and prostate cancer metastases. In the present study, we have analyzed the effects of Curcumin on miRNA expression and its correlation to the anti-tumorigenic properties of this natural occurring polyphenol. Using microarray miRNA expression analyses, we show here that Curcumin modulates the expression of a series of miRNAs, including miR181b, in metastatic breast cancer cells. Interestingly, we found that miR181b down-modulates CXCL1 and -2 through a direct binding to their 3'-UTR. Overexpression or inhibition of miR181b in metastatic breast cancer cells has a significant impact on CXCL1 and -2 and is required for the effect of Curcumin on these two cytokines. miR181b also mediates the effects of Curcumin on inhibition of proliferation and invasion as well as induction of apoptosis. Importantly, over-expression of miR181b in metastatic breast cancer cells inhibits metastasis formation in vivo in immunodeficient mice. Finally, we demonstrated that Curcumin up-regulates miR181b and down-regulates CXCL1 and -2 in cells isolated from several primary human breast cancers. Taken together, these data show that Curcumin provides a simple bridge to bring metastamir modulation into the clinic, placing it in a primary and tertiary preventive, as well as a therapeutic, setting. PMID:24484937

  11. Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

    PubMed Central

    Li, Jingjing; Chen, Tong; Deng, Feng; Wan, Jingyuan; Tang, Yalan; Yuan, Pei; Zhang, Liangke

    2015-01-01

    We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 μg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity. PMID:26346750

  12. Antioxidant activities of curcumin and ascorbyl dipalmitate nanoparticles and their activities after incorporation into cellulose-based packaging films.

    PubMed

    Sonkaew, Piyapong; Sane, Amporn; Suppakul, Panuwat

    2012-05-30

    Curcumin (Ccm) and ascorbyl dipalmitate (ADP) nanoparticles (NPs) with average sizes of ∼50 and ∼80 nm, respectively, were successfully produced by rapid expansion of subcritical solutions into liquid solvents (RESOLV). Pluronic F127 was employed as a stabilizer for both Ccm- and ADP-NPs in an aqueous receiving solution. Antioxidant activities of the Ccm-NPs and ADP-NPs were subsequently investigated using four assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ABTS radical cation decolorization, β-carotene bleaching, and ferric reducing antioxidant power. Ccm-NPs and ADP-NPs showed higher antioxidant activities than those of Ccm and ADP. Ccm-NPs yielded higher antioxidant activities than those of Ccm in ethanol and water (Ccm-EtOH and Ccm-H(2)O), respectively. ADP-NPs yielded lower antioxidant activities than that of ADP in ethanol (ADP-EtOH) but higher activities than that of ADP in water (ADP-H(2)O). Moreover, incorporation of Ccm-NPs and ADP-NPs into cellulose-based films indicated that Ccm-NPs and ADP-NPs significantly enhanced the antioxidant activities of Ccm and ADP (p < 0.05). Our results show that the environmentally benign supercritical CO(2) technique should be generally applicable to NP fabrication of other important bioactive ingredients, especially in liquid form. In addition, we suggest that Ccm-NPs and ADP-NPs can be used to reduce the dosage of Ccm and ADP and improve their bioavailability, and thus merit further investigation for antioxidant packaging film and coating applications. PMID:22583595

  13. A Novel Nanoparticle Drug Delivery System: The Anti-inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes

    PubMed Central

    Sun, Dongmei; Zhuang, Xiaoying; Xiang, Xiaoyu; Liu, Yuelong; Zhang, Shuangyin; Liu, Cunren; Barnes, Stephen; Grizzle, William; Miller, Donald; Zhang, Huang-Ge

    2010-01-01

    Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood. We show that the target specificity is determined by exosomes, and the improvement of curcumin activity is achieved by directing curcumin to inflammatory cells associated with therapeutic, but not toxic, effects. Furthermore, we validate the therapeutic relevance of this technique in a lipopolysaccharide (LPS)-induced septic shock mouse model. We further show that exosomes, but not lipid alone, are required for the enhanced anti-inflammatory activity of curcumin. The specificity of using exosomes as a drug carrier creates opportunities for treatments of many inflammation-related diseases without significant side effects due to innocent bystander or off-target effects. PMID:20571541

  14. Assessment of the relative performance of a confined impinging jets mixer and a multi-inlet vortex mixer for curcumin nanoparticle production.

    PubMed

    Chow, Shing Fung; Sun, Changquan Calvin; Chow, Albert Hee Lum

    2014-10-01

    The relative performance of two specially designed mixers for nanoparticle production, namely, two-stream confined impinging jets with dilution mixer (CIJ-D-M) and four-stream multi-inlet vortex mixer (MIVM), was evaluated using the model compound, curcumin (CUR), under defined conditions of varying mixing rate and organic solvent. In the absence of turbulent fluctuations, higher mixing rate tended to generate finer particles. Among the three water-miscible organic solvents tested, acetone afforded the smallest particle size and the narrowest particle size distribution. Both mixers were capable of reproducibly fabricating CUR nanoparticles with particle size below 100 nm and high encapsulation efficiency (>99.9%). Specifically, CIJ-D-M yielded nanoparticles with smaller size and polydispersity index while the particles obtained by the MIVM displayed better short-term stability. In addition, CIJ-D-M tended to produce a mixture of irregular nanoaggregates and primary nanoparticles while roughly spherical nanoparticles were generated with the MIVM. The observed particle size and morphological differences could be attributed to the differences in the configuration of the mixing chamber and the related mixing order. PMID:25016977

  15. The synthesis of poly(lactide)-vitamin E TPGS (PLA-TPGS) copolymer and its utilization to formulate a curcumin nanocarrier

    NASA Astrophysics Data System (ADS)

    Thu Ha, Phuong; Nguyet Tran, Thi Minh; Duong Pham, Hong; Huan Nguyen, Quang; Phuc Nguyen, Xuan

    2010-03-01

    Curcumin is a natural substance that exhibits the ability to inhibit and/or treat carcinogenesis in a variety of cell lines, but because of its poor solubility in water the treatment efficacy is limited. In this paper we report on the fabrication of self-assembled micelle nanoparticles loaded with a curcumin drug by use of a biocompatible copolymer of PLA-TPGS (d-a-tocopheryl polyethylene glycol 1000 succinate—vitamin E TPGS) conjugate. The polylactide (PLA)-TPGS copolymer synthesized by ring-opening polymerization was characterized by Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) techniques. The surface morphology of PLA-TPGS and curcumin loaded PLA-TPGS was determined by field emission scanning electron microscopy (FE-SEM). The absorption and fluorescence examinations indicated that due to micellar capsulation the intensity of both types of spectra increased by about 4 times in comparison with those of the free curcumin sample.

  16. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The growth of new blood vessels or angiogenesis is necessary for the growth of adipose tissue. Dietary polyphenols may suppress growth of adipose tissue through their antiangiogenic activity and by modulating adipocyte metabolism. In the present study, we examined the effect of curcumin, a polyphen...

  17. Curcumin, Silybin Phytosome(®) and α-R-Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production.

    PubMed

    Ali, Shimaa O; Darwish, Hebatallah A; Ismail, Nabila A

    2016-05-01

    Chronic hepatitis is recognized as a worldwide health problem that gradually progresses towards cirrhosis and hepatocellular carcinoma. Despite the large number of experiments using animal models for allergic hepatitis, it is still difficult to produce a picture of chronic hepatitis. Therefore, this study was conducted to introduce an animal model approximating to the mechanism of chronicity in human hepatitis. The study also aimed to examine the hepatoprotective effects of curcumin, silybin phytosome(®) and α-R-lipoic acid against thioacetamide (TAA)-induced chronic hepatitis in rat model. TAA was administered intraperitoneally at a dose of 200 mg/kg three times weekly for 4 weeks. At the end of this period, a group of rats was killed to assess the development of chronic hepatitis in comparison with their respective control group. TAA administration was then discontinued, and the remaining animals were subsequently allocated into four groups. Group 1 was left untreated, whereas groups 2-4 were allowed to receive daily oral doses of curcumin, silybin phytosome(®) or α-R-lipoic acid, respectively, for 7 weeks. Increases in hepatic levels of malondialdehyde associated with TAA administration were inhibited in groups receiving supplements. Furthermore, glutathione depletion, collagen deposition, macrophage activation and nuclear factor κappa-B expression as well as tumour necrosis factor-α and interleukin-6 levels were significantly decreased in response to supplements administration. Serological analysis of liver function and liver histopathological examination reinforced the results. The above evidence collectively indicates that the antioxidant and anti-inflammatory activities of curcumin, silybin phytosome(®) and α-R-lipoic acid may confer therapeutic efficacy against chronic hepatitis. PMID:26457982

  18. Gold Nanoparticles and Microwave Irradiation Inhibit Beta-Amyloid Amyloidogenesis

    NASA Astrophysics Data System (ADS)

    Araya, Eyleen; Olmedo, Ivonne; Bastus, Neus G.; Guerrero, Simón; Puntes, Víctor F.; Giralt, Ernest; Kogan, Marcelo J.

    2008-11-01

    Peptide-Gold nanoparticles selectively attached to β-amyloid protein (Aβ) amyloidogenic aggregates were irradiated with microwave. This treatment produces dramatic effects on the Aβ aggregates, inhibiting both the amyloidogenesis and the restoration of the amyloidogenic potential. This novel approach offers a new strategy to inhibit, locally and remotely, the amyloidogenic process, which could have application in Alzheimer’s disease therapy. We have studied the irradiation effect on the amyloidogenic process in the presence of conjugates peptide-nanoparticle by transmission electronic microscopy observations and by Thioflavine T assays to quantify the amount of fibrils in suspension. The amyloidogenic aggregates rather than the amyloid fibrils seem to be better targets for the treatment of the disease. Our results could contribute to the development of a new therapeutic strategy to inhibit the amyloidogenic process in Alzheimer’s disease.

  19. Phytotoxicity of nanoparticles: inhibition of seed germination and root growth.

    PubMed

    Lin, Daohui; Xing, Baoshan

    2007-11-01

    Plants need to be included to develop a comprehensive toxicity profile for nanoparticles. Effects of five types of nanoparticles (multi-walled carbon nanotube, aluminum, alumina, zinc, and zinc oxide) on seed germination and root growth of six higher plant species (radish, rape, ryegrass, lettuce, corn, and cucumber) were investigated. Seed germination was not affected except for the inhibition of nanoscale zinc (nano-Zn) on ryegrass and zinc oxide (nano-ZnO) on corn at 2000 mg/L. Inhibition on root growth varied greatly among nanoparticles and plants. Suspensions of 2000 mg/L nano-Zn or nano-ZnO practically terminated root elongation of the tested plant species. Fifty percent inhibitory concentrations (IC50) of nano-Zn and nano-ZnO were estimated to be near 50mg/L for radish, and about 20mg/L for rape and ryegrass. The inhibition occurred during the seed incubation process rather than seed soaking stage. These results are significant in terms of use and disposal of engineered nanoparticles. PMID:17374428

  20. Oral bioavailability of curcumin: problems and advancements.

    PubMed

    Liu, Weidong; Zhai, Yingjie; Heng, Xueyuan; Che, Feng Yuan; Chen, Wenjun; Sun, Dezhong; Zhai, Guangxi

    2016-09-01

    Curcumin is a natural compound of Curcuma longa L. and has shown many pharmacological activities such as anti-inflammatory, anti-oxidant in both preclinical and clinical studies. Moreover, curcumin has hepatoprotective, neuroprotective activities and protects against myocardial infarction. Particularly, curcumin has also demonstrated favorite anticancer efficacy. But limiting factors such as its extremely low oral bioavailability hampers its application as therapeutic agent. Therefore, many technologies have been developed and applied to overcome this limitation. This review described the main physicochemical properties of curcumin and summarized the recent studies in the design and development of oral delivery systems for curcumin to enhance the solubility and oral bioavailability, including liposomes, nanoparticles and polymeric micelles, phospholipid complexes, and microemulsions. PMID:26942997

  1. Can small hydrophobic gold nanoparticles inhibit β2-microglobulin fibrillation?

    NASA Astrophysics Data System (ADS)

    Brancolini, Giorgia; Toroz, Dimitrios; Corni, Stefano

    2014-06-01

    Inorganic nanoparticles stabilized by a shell of organic ligands can enhance or suppress the natural propensity of proteins to form fibrils. Functionalization facilitates targeted delivery of the nanoparticles to various cell types, bioimaging, drug delivery and other therapeutic and diagnostic applications. In this study, we provide a computational model of the effect of a prototypical thiol-protected gold nanoparticle, Au25L18- (L = S(CH2)2Ph) on the β2-microglobulin natural fibrillation propensity. To reveal the molecular basis of the protein-nanoparticle association process, we performed various simulations at multiple levels (Classical Molecular Dynamics and Brownian Dynamics) that cover multiple length- and timescales. The results provide a model of the ensemble of structures constituting the protein-gold nanoparticle complexes, and insights into the driving forces for the binding of β2-microglobulin to hydrophobic small size gold nanoparticles. We have found that the small nanoparticles can bind the protein to form persistent complexes. This binding of nanoparticles is able to block the active sites of domains from binding to another protein, thus leading to potential inhibition of the fibrillation activity. A comparison with the binding patches identified for the interaction of the protein with a known inhibitor of fibrillation, supports our conclusion.Inorganic nanoparticles stabilized by a shell of organic ligands can enhance or suppress the natural propensity of proteins to form fibrils. Functionalization facilitates targeted delivery of the nanoparticles to various cell types, bioimaging, drug delivery and other therapeutic and diagnostic applications. In this study, we provide a computational model of the effect of a prototypical thiol-protected gold nanoparticle, Au25L18- (L = S(CH2)2Ph) on the β2-microglobulin natural fibrillation propensity. To reveal the molecular basis of the protein-nanoparticle association process, we performed various

  2. Improved bioavailability of targeted Curcumin delivery efficiently regressed cardiac hypertrophy by modulating apoptotic load within cardiac microenvironment.

    PubMed

    Ray, Aramita; Rana, Santanu; Banerjee, Durba; Mitra, Arkadeep; Datta, Ritwik; Naskar, Shaon; Sarkar, Sagartirtha

    2016-01-01

    Cardiomyocyte apoptosis acts as a prime modulator of cardiac hypertrophy leading to heart failure, a major cause of human mortality worldwide. Recent therapeutic interventions have focussed on translational applications of diverse pharmaceutical regimes among which, Curcumin (from Curcuma longa) is known to have an anti-hypertrophic potential but with limited pharmacological efficacies due to low aqueous solubility and poor bioavailability. In this study, Curcumin encapsulated by carboxymethyl chitosan (CMC) nanoparticle conjugated to a myocyte specific homing peptide was successfully delivered in bioactive form to pathological myocardium for effective regression of cardiac hypertrophy in a rat (Rattus norvegicus) model. Targeted nanotization showed higher cardiac bioavailability of Curcumin at a low dose of 5 mg/kg body weight compared to free Curcumin at 35 mg/kg body weight. Moreover, Curcumin/CMC-peptide treatment during hypertrophy significantly improved cardiac function by downregulating expression of hypertrophy marker genes (ANF, β-MHC), apoptotic mediators (Bax, Cytochrome-c) and activity of apoptotic markers (Caspase 3 and PARP); whereas free Curcumin in much higher dose showed minimal improvement during compromised cardiac function. Targeted Curcumin treatment significantly lowered p53 expression and activation in diseased myocardium via inhibited interaction of p53 with p300-HAT. Thus attenuated acetylation of p53 facilitated p53 ubiquitination and reduced the apoptotic load in hypertrophied cardiomyocytes; thereby limiting cardiomyocytes' need to enter the regeneration cycle during hypertrophy. This study elucidates for the first time an efficient targeted delivery regimen for Curcumin and also attributes towards probable mechanistic insight into its therapeutic potential as a cardio-protective agent for regression of cardiac hypertrophy. PMID:26612707

  3. Curcumin: A new candidate for melanoma therapy?

    PubMed

    Mirzaei, Hamed; Naseri, Gholamreza; Rezaee, Ramin; Mohammadi, Mohsen; Banikazemi, Zarrin; Mirzaei, Hamid Reza; Salehi, Hossein; Peyvandi, Mostafa; Pawelek, John M; Sahebkar, Amirhossein

    2016-10-15

    Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g., BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin. PMID:27280688

  4. Layer-by-layer engineered nanocapsules of curcumin with improved cell activity.

    PubMed

    Kittitheeranun, Paveenuch; Sajomsang, Warayuth; Phanpee, Sarunya; Treetong, Alongkot; Wutikhun, Tuksadon; Suktham, Kunat; Puttipipatkhachorn, Satit; Ruktanonchai, Uracha Rungsardthong

    2015-08-15

    Nanocarriers based on electrostatic Layer-by-layer (LbL) assembly of CaCO3 nanoparticles (CaCO3 NPs) was investigated. These inorganic nanoparticles was used as templates to construct nanocapsules made from films based on two oppositely charged polyelectrolytes, poly(diallyldimethylammonium chloride), and poly (sodium 4-styrene-sulfonate sodium salt), followed by core dissolution. The naked CaCO3 NPs, CaCO3 NPs coated with the polyelectrolytes and hollow nanocapsules were found with hexagonal shape with average sizes of 350-400 nm. A reversal of the surface charge between positive to negative zeta potential values was found, confirming the adsorption of polyelectrolytes. The loading efficiency and release of curcumin were controlled by the hydrophobic interactions between the drug and the polyelectrolyte matrix of the hollow nanocapsules. The quantity of curcumin released from hollow nanocapsules was found to increase under acidic environments, which is a desirable for anti-cancer drug delivery. The hollow nanocapsules were found to localize in the cytoplasm and nucleus compartment of Hela cancer cells after 24 h of incubation. Hollow nanocapsules were non-toxic to human fibroblast cells. Furthermore, curcumin loaded hollow nanocapsules exhibited higher in vitro cell inhibition against Hela cells than that of free curcumin, suggesting that polyelectrolyte based-hollow nanocapsules can be utilized as new carriers for drug delivery. PMID:26143232

  5. Resveratrol and curcumin synergistically induces apoptosis in cigarette smoke condensate transformed breast epithelial cells through a p21(Waf1/Cip1) mediated inhibition of Hh-Gli signaling.

    PubMed

    Mohapatra, Purusottam; Satapathy, Shakti Ranjan; Siddharth, Sumit; Das, Dipon; Nayak, Anmada; Kundu, Chanakya Nath

    2015-09-01

    Combination therapy using two or more small molecule inhibitors of aberrant signaling cascade in aggressive breast cancers is a promising therapeutic strategy over traditional monotherapeutic approaches. Here, we have studied the synergistic mechanism of resveratrol and curcumin induced apoptosis using in vitro (cigarette smoke condensate mediated transformed breast epithelial cell, MCF-10A-Tr) and in vivo (tumor xenograft mice) model system. Resveratrol exposure increased the intracellular uptake of curcumin in a dose dependent manner and caused apoptosis in MCF-10A-Tr cells. Approximately, ten fold lower IC50 value was noted in cells treated with the combination of resveratrol (3μM) and curcumin (3μM) in comparison to 30μM of resveratrol or curcumin alone. Resveratrol+curcumin combination caused apoptosis by increasing Bax/Bcl-xL ratio, Cytochrome C release, cleaved product of PARP and caspase 3 in cells. Interestingly, this combination unaltered the protein expressions of WNT-TCF and Notch signaling components, β-catenin and cleaved notch-1 val1744, respectively. Furthermore, the combination also significantly decreased the intermediates of Hedgehog-Gli cascade including SMO, SHH, Gli-1, c-MYC, Cyclin-D1, etc. and increased the level of p21(Waf/Cip1) in vitro and in vivo. A significant reduction of Gli- promoter activity was noted in combinational drug treated cells in comparison to individual drug treatment. Un-alteration of the expressions of the above proteins and Gli1 promoter activity in p21(Waf/Cip1) knockout cells suggests this combination caused apoptosis through p21(Waf/Cip1). Thus, our findings revealed resveratrol and curcumin synergistically caused apoptosis in cigarette smoke induced breast cancer cells through p2(Waf/Cip1) mediated inhibition of Hedgehog-Gli cascade. PMID:26212257

  6. Curcumin Nanoformulation for Cervical Cancer Treatment

    PubMed Central

    Zaman, Mohd S.; Chauhan, Neeraj; Yallapu, Murali M.; Gara, Rishi K.; Maher, Diane M.; Kumari, Sonam; Sikander, Mohammed; Khan, Sheema; Zafar, Nadeem; Jaggi, Meena; Chauhan, Subhash C.

    2016-01-01

    Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based curcumin nanoparticle formulation (Nano-CUR). This study demonstrates that in comparison to free CUR, Nano-CUR effectively inhibits cell growth, induces apoptosis, and arrests the cell cycle in cervical cancer cell lines. Nano-CUR treatment modulated entities such as miRNAs, transcription factors, and proteins associated with carcinogenesis. Moreover, Nano-CUR effectively reduced the tumor burden in a pre-clinical orthotopic mouse model of cervical cancer by decreasing oncogenic miRNA-21, suppressing nuclear β-catenin, and abrogating expression of E6/E7 HPV oncoproteins including smoking compound benzo[a]pyrene (BaP) induced E6/E7 and IL-6 expression. These superior pre-clinical data suggest that Nano-CUR may be an effective therapeutic modality for cervical cancer. PMID:26837852

  7. Curcumin Ameliorates Ischemia-Induced Limb Injury Through Immunomodulation

    PubMed Central

    Liu, Yang; Chen, Lianyu; Shen, Yi; Tan, Tao; Xie, Nanzi; Luo, Ming; Li, Zhihong; Xie, Xiaoyun

    2016-01-01

    Background The prevalence of peripheral arterial disease (PAD) is increasing worldwide. Currently, there is no effective treatment for PAD. Curcumin is an ingredient of turmeric that has antioxidant, anti-inflammation, and anticancer properties. In the present study we investigated the potential effect of curcumin in protecting against ischemic limb injury. Material/Methods We used an established hindlimb ischemia mouse model in our study. Curcumin was administrated through intraperitoneal (I.P.) injection. Immunohistochemical staining and ELISA assays were performed. Treadmill training was used to evaluate skeletal muscle functions of animals. Results Our experiments using in vivo treadmill training showed that curcumin treatment improved the running capacity of animals after ischemic injury. Histological analysis revealed that curcumin treatment significantly reduced the skeletal muscle damage and fibrosis associated with ischemic injury. In order to determine the cellular and molecular mechanisms underlying curcumin-mediated tissue protection, immunohistochemical staining and ELISA assays were performed. The results showed that curcumin treatment led to less macrophage infiltration and less local inflammatory responses as demonstrated by decreasing TNF-α, IL-1, and IL-6 levels. Further immunofluorescent staining of tissue slides indicated that curcumin treatment inhibited the NF-κB signaling pathway. Finally, curcumin can inhibit NF-κB activation induced by LPS in macrophages. Conclusions Our study results show that curcumin treatment can ameliorate hindlimb injury following ischemic surgery, which suggests that curcumin could be used for PAD treatment. PMID:27302110

  8. Curcumin Ameliorates Ischemia-Induced Limb Injury Through Immunomodulation.

    PubMed

    Liu, Yang; Chen, Lianyu; Shen, Yi; Tan, Tao; Xie, Nanzi; Luo, Ming; Li, Zhihong; Xie, Xiaoyun

    2016-01-01

    BACKGROUND The prevalence of peripheral arterial disease (PAD) is increasing worldwide. Currently, there is no effective treatment for PAD. Curcumin is an ingredient of turmeric that has antioxidant, anti-inflammation, and anticancer properties. In the present study we investigated the potential effect of curcumin in protecting against ischemic limb injury. MATERIAL AND METHODS We used an established hindlimb ischemia mouse model in our study. Curcumin was administrated through intraperitoneal (I.P.) injection. Immunohistochemical staining and ELISA assays were performed. Treadmill training was used to evaluate skeletal muscle functions of animals. RESULTS Our experiments using in vivo treadmill training showed that curcumin treatment improved the running capacity of animals after ischemic injury. Histological analysis revealed that curcumin treatment significantly reduced the skeletal muscle damage and fibrosis associated with ischemic injury. In order to determine the cellular and molecular mechanisms underlying curcumin-mediated tissue protection, immunohistochemical staining and ELISA assays were performed. The results showed that curcumin treatment led to less macrophage infiltration and less local inflammatory responses as demonstrated by decreasing TNF-α, IL-1, and IL-6 levels. Further immunofluorescent staining of tissue slides indicated that curcumin treatment inhibited the NF-κB signaling pathway. Finally, curcumin can inhibit NF-kB activation induced by LPS in macrophages. CONCLUSIONS Our study results show that curcumin treatment can ameliorate hindlimb injury following ischemic surgery, which suggests that curcumin could be used for PAD treatment. PMID:27302110

  9. Supramolecular curcumin-barium prodrugs for formulating with ceramic particles.

    PubMed

    Kamalasanan, Kaladhar; Anupriya; Deepa, M K; Sharma, Chandra P

    2014-10-01

    A simple and stable curcumin-ceramic combined formulation was developed with an aim to improve curcumin stability and release profile in the presence of reactive ceramic particles for potential dental and orthopedic applications. For that, curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur) complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water-soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at 10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies revealed that, divalent Ba(2+) interacted predominantly through di-phenolic groups of curcumin to form an end-to-end complex resulted in supramolecular multimer. The overall crystallinity of the BaCur was lower than curcumin as per XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+) complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon loading into pluronic micelles the size was remaining in similar order of magnitude as per DLS and AFM studies. Stability of the curcumin was improved greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy. Loading of the supramloecular nanoparticles into pluronic micelles had further improved the stability of curcumin to approx. 70% in water. These BaCur supramolecule nanoparticles can be considered as a new class of prodrugs with improved solubility and stability. Subsequently, ceramic nanoparticles with varying chemical composition were prepared for changing the material surface reactivity in terms of the increase in, degradability, surface pH and protein adsorption. Further, these ceramic particles were combined with curcumin prodrug formulations and optimized the curcumin release

  10. New perspectives of curcumin in cancer prevention

    PubMed Central

    Park, Wungki; Amin, A.R.M Ruhul; Chen, Zhuo Georgia; Shin, Dong M.

    2013-01-01

    Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications. PMID:23466484

  11. MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

    SciTech Connect

    Yu, Teng; Ji, Jiang; Guo, Yong-li

    2013-11-08

    Highlights: •Curcumin activates MST1 in melanoma cells. •MST1 mediates curcumin-induced apoptosis of melanoma cells. •ROS production is involved in curcumin-induced MST1 activation. •MST1 mediates curcumin-induced JNK activation in melanoma cells. •MST1 mediates curcumin-induced Foxo3a nuclear translocation and Bim expression. -- Abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen species (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells.

  12. Targeting JNK by a New Curcumin Analog to Inhibit NF-kB-Mediated Expression of Cell Adhesion Molecules Attenuates Renal Macrophage Infiltration and Injury in Diabetic Mice

    PubMed Central

    Cai, Lu; Ren, Luqing; Tang, Longguang; Wang, Jingying; Zhao, Yunjie; Wang, Yonggang; Liu, Quan; Li, Xiaokun; Liang, Guang

    2013-01-01

    Macrophage infiltration contributes to the pathogenesis of diabetic renal injury. However, the regulatory mechanisms between macrophage infiltration and epithelial cell activation are still unclear. Our previous study found that C66, a novel curcumin analog, was able to inhibit inflammatory cytokine expression in vitro and in vivo. This study further elucidated whether C66 can prevent glucose-induced renal epithelial activation and inflammatory macrophage infiltration by a MAPK/NF-κB medicated mechanism. Our data show that pretreatment with C66 not only significantly reduced high glucose (HG)-induced over-expressions of VCAM-1, ICAM-1 and MCP-1, but also remarkably inhibited NF-κB activation, MAPKs phosphorylation, and subsequently macrophage adhesion in renal epithelial NRK-52E cells. Furthermore, we find that MAPKs, especially JNK, play important roles in HG-induced NF-κB activation, which regulates the over-expression of adhesion molecules in HG-stimulated NRK-52E cells. A molecular docking predicted that C66 may target JNK2, which leads to its anti-inflammatory actions. In vivo, administration of C66 or JNK special inhibitor SP600125 at 5 mg/kg markedly decreased diabetes-induced renal adhesion molecule expression, NF-κB activation, inflammatory cell infiltration, and pathological indexes in the kidneys of diabetic mice. These findings provide a perspective on the renoprotective effects of C66 in diabetes, and outline a novel therapeutic strategy of JNK inhibition for the treatment of diabetic nephropathy. PMID:24260158

  13. BDMC33, A Curcumin Derivative Suppresses Inflammatory Responses in Macrophage-Like Cellular System: Role of Inhibition in NF-κB and MAPK Signaling Pathways

    PubMed Central

    Lee, Ka-Heng; Chow, Yuh-Lit; Sharmili, Vidyadaran; Abas, Faridah; Alitheen, Noorjahan Banu Mohamed; Shaari, Khozirah; Israf, Daud Ahmad; Lajis, Nordin Haji; Syahida, Ahmad

    2012-01-01

    Our preliminary screening has shown that curcumin derivative BDMC33 [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] exerted promising nitric oxide inhibitory activity in activated macrophages. However, the molecular basis and mechanism for its pharmacological action is yet to be elucidated. The aim of this study was to investigate the anti-inflammatory properties of BDMC33 and elucidate its underlying mechanism action in macrophage cells. Our current study demonstrated that BDMC33 inhibits the secretion of major pro-inflammatory mediators in stimulated macrophages, and includes NO, TNF-α and IL-1β through interference in both nuclear factor kappaB (NF-κB) and mitogen activator protein kinase (MAPK) signaling cascade in IFN-γ/LPS-stimulated macrophages. Moreover, BDMC33 also interrupted LPS signaling through inhibiting the surface expression of CD-14 accessory molecules. In addition, the inhibitory action of BDMC33 not only restricted the macrophages cell (RAW264.7), but also inhibited the secretion of NO and TNF-α in IFN-γ/LPS-challenged microglial cells (BV-2). The experimental data suggests the inflammatory action of BDMC33 on activated macrophage-like cellular systems, which could be used as a future therapeutic agent in the management of chronic inflammatory diseases. PMID:22489138

  14. Curcumin suppresses migration and invasion of human endometrial carcinoma cells

    PubMed Central

    CHEN, QIAN; GAO, QING; CHEN, KUNLUN; WANG, YIDONG; CHEN, LIJUAN; LI, XU

    2015-01-01

    Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, following treatment with curcumin for 24 h, there was a decrease in the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in EC cells. Moreover, curcumin treatment significantly decreased the levels of the phosphorylated form of extracellular signal-regulated kinase (ERK) 1/2. MEK1 overexpression partially blocked the anti-metastatic effects of curcumin. Combined treatment with ERK inhibitor U0126 and curcumin resulted in a synergistic reduction in MMP-2/-9 expression; the invasive capabilities of HEC-1B cells were also inhibited. In conclusion, curcumin inhibits tumor cell migration and invasion by reducing the expression and activity of MMP-2/9 via the suppression of the ERK signaling pathway, suggesting that curcumin is a potential therapeutic agent for EC. PMID:26622667

  15. Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines.

    PubMed

    Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Yamin, Bohari M; Leong, Sze Wei; Abdul Bahari, Mohd Nazri; Lim, Sock Jin; Mohd Faudzi, Siti Munirah; Jalil, Juriyati; Abas, Faridah; Mohd Fauzi, Norsyahida; Ismail, Nor Hadiani; Jantan, Ibrahim; Lam, Kok Wai

    2016-05-15

    The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50=12.01μM and 8c, IC50=4.86μM) and U937 (8b, IC50=3.44μM and 8c, IC50=1.65μM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50=0.78μM and 15b, IC50=1.9μM while U937: 15a, IC50=0.95μM and 15b, IC50=0.92μM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-β, ERK, JNK2, p38α and p38β were performed using the conformation of 15a determined by single-crystal XRD. PMID:27040659

  16. The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae-induced NF-kappaB signaling, release of pro-inflammatory cytokines/chemokines and attenuates adhesion in late infection.

    PubMed

    Wessler, Silja; Muenzner, Petra; Meyer, Thomas F; Naumann, Michael

    2005-05-01

    Neisseria gonorrhoeae (Ngo) is a Gram-negative pathogenic bacterium responsible for an array of diseases ranging from urethritis to disseminated gonococcal infections. Early events in the establishment of infection involve interactions between Ngo and the mucosal epithelium, which induce a local inflammatory response. Here we analyzed the molecular mechanism involved in the Ngo-induced induction of the proinflammatory cytokines tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), and IL-8. We identified the immediate early response transcription factor nuclear factor kappaB (NF-kappaB) as a key molecule for the induction of cytokine release. Ngo-induced activation of direct upstream signaling molecules was demonstrated for IkappaB kinase alpha and beta (IKKalpha and IKKbeta) by phosphorylation of IkappaBalpha as a substrate and IKK autophosphorylation. Using dominant negative cDNAs encoding kinase-dead IKKalpha, IKKbeta, and NF-kappaB-inducing kinase (NIK), Ngo-induced NF-kappaB activity was significantly inhibited. Curcumin, the yellow pigment derived from Curcuma longa, inhibited IKKalpha, IKKbeta and NIK, indicating its strong potential to block NF-kappaB-mediated cytokine release and the innate immune response. In addition to the inhibition of Ngo-induced signaling, curcumin treatment of cells completely abolished the adherence of bacteria to cells in late infection, underlining the high potential of curcumin as an anti-microbial compound without cytotoxic side effects. PMID:15927892

  17. Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases.

    PubMed

    Zhuang, Xiao-Dong; Liao, Li-Zhen; Dong, Xiao-Bian; Hu, Xun; Guo, Yue; Du, Zhi-Min; Liao, Xin-Xue; Wang, Li-Chun

    2016-01-01

    This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice. PMID:26792980

  18. Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases

    PubMed Central

    Zhuang, Xiao-dong; Liao, Li-zhen; Dong, Xiao-bian; Hu, Xun; Guo, Yue; Du, Zhi-min; Liao, Xin-xue; Wang, Li-chun

    2016-01-01

    This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice. PMID:26792980

  19. Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl-2 through activation of autophagy in MCF-7 cells.

    PubMed

    Akkoç, Yunus; Berrak, Özge; Arısan, Elif Damla; Obakan, Pınar; Çoker-Gürkan, Ajda; Palavan-Ünsal, Narçin

    2015-04-01

    Curcumin is a natural anti-cancer agent derived from turmeric (Curcuma longa). Curcumin triggers intrinsic apoptotic cell death by activating mitochondrial permeabilization due to the altered expression of pro- and anti-apoptotic Bcl-2 family members. Phosphoinositol-3-kinase (PI3K) and Akt, key molecular players in the survival mechanism, have been shown to be associated with the Bcl-2 signaling cascade; therefore, evaluating the therapeutic efficiency of drugs that target both survival and the apoptosis mechanism has gained importance in cancer therapy. We found that Bcl-2 overexpression is a limiting factor for curcumin-induced apoptosis in highly metastatic MCF-7 breast cancer cells. Forced overexpression of Bcl-2 also blocked curcumin-induced autophagy in MCF-7 cells, through its inhibitory interactions with Beclin-1. Pre-treatment of PI3K inhibitor LY294002 enhanced curcumin-induced cell death, apoptosis, and autophagy via modulating the expression of Bcl-2 family members and autophagosome formation in MCF-7 breast cancer cells. Atg7 silencing further increased apoptotic potential of curcumin in the presence or absence of LY294002 in wt and Bcl-2+ MCF-7 cells. The findings of this study support the hypothesis that blocking the PI3K/Akt pathway may further increased curcumin-induced apoptosis and overcome forced Bcl-2 expression level mediated autophagic responses against curcumin treatment in MCF-7 cells. PMID:25960232

  20. Self-carried curcumin nanoparticles for in vitro and in vivo cancer therapy with real-time monitoring of drug release

    NASA Astrophysics Data System (ADS)

    Zhang, Jinfeng; Li, Shengliang; An, Fei-Fei; Liu, Juan; Jin, Shubin; Zhang, Jin-Chao; Wang, Paul C.; Zhang, Xiaohong; Lee, Chun-Sing; Liang, Xing-Jie

    2015-08-01

    The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically <10%) and reduce their potential systemic toxicity. Therefore, the development of alternative self-carried nanodrug delivery strategies without using inert carriers is highly desirable. In this study, we developed a self-carried curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environments with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescence ``OFF-ON'' activation and real-time monitoring of the Cur molecule release. In vitro and in vivo experiments clearly show that the therapeutic efficacy of the PEGylated Cur NPs is considerably better than that of free Cur. This self-carried strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and monitoring.The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically <10%) and reduce their potential systemic toxicity. Therefore, the development of alternative self-carried nanodrug delivery strategies without using inert carriers is highly desirable. In this study, we developed a self-carried curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding

  1. Curcumin nanoformulations: a future nanomedicine for cancer

    PubMed Central

    Yallapu, Murali M; Jaggi, Meena; Chauhan, Subhash C

    2011-01-01

    Curcumin, a natural diphenolic compound derived from turmeric Curcuma longa, has proven to be a modulator of intracellular signaling pathways that control cancer cell growth, inflammation, invasion, apoptosis and cell death, revealing its anticancer potential. In this review, we focus on the design and development of nanoparticles, self-assemblies, nanogels, liposomes and complex fabrication for sustained and efficient curcumin delivery. We also discuss the anticancer applications and clinical benefits of nanocurcumin formulations. Only a few novel multifunctional and composite nanosystem strategies offer simultaneous therapy as well as imaging characteristics. We also summarize the challenges to developing curcumin delivery platforms and up-to-date solutions for improving curcumin bioavailability and anticancer potential for therapy. PMID:21959306

  2. Nanotechnology-Applied Curcumin for Different Diseases Therapy

    PubMed Central

    Ghalandarlaki, Negar; Ashkani-Esfahani, Soheil

    2014-01-01

    Curcumin is a lipophilic molecule with an active ingredient in the herbal remedy and dietary spice turmeric. It is used by different folks for treatment of many diseases. Recent studies have discussed poor bioavailability of curcumin because of poor absorption, rapid metabolism, and rapid systemic elimination. Nanotechnology is an emerging field that is potentially changing the way we can treat diseases through drug delivery with curcumin. The recent investigations established several approaches to improve the bioavailability, to increase the plasma concentration, and to enhance the cellular permeability processes of curcumin. Several types of nanoparticles have been found to be suitable for the encapsulation or loading of curcumin to improve its therapeutic effects in different diseases. Nanoparticles such as liposomes, polymeric nanoparticles, micelles, nanogels, niosomes, cyclodextrins, dendrimers, silvers, and solid lipids are emerging as one of the useful alternatives that have been shown to deliver therapeutic concentrations of curcumin. This review shows that curcumin's therapeutic effects may increase to some extent in the presence of nanotechnology. The presented board of evidence focuses on the valuable special effects of curcumin on different diseases and candidates it for future clinical studies in the realm of these diseases. PMID:24995293

  3. Synthesis of biocompatible nanoparticle drug complexes for inhibition of mycobacteria

    NASA Astrophysics Data System (ADS)

    Bhave, Tejashree; Ghoderao, Prachi; Sanghavi, Sonali; Babrekar, Harshada; Bhoraskar, S. V.; Ganesan, V.; Kulkarni, Anjali

    2013-12-01

    Tuberculosis (TB) is one of the most critical infectious diseases affecting the world today. Current TB treatment involves six months long daily administration of four oral doses of antibiotics. Due to severe side effects and the long treatment, a patient's adherence is low and this results in relapse of symptoms causing an alarming increase in the prevalence of multi-drug resistant (MDR) TB. Hence, it is imperative to develop a new drug delivery technology wherein these effects can be reduced. Rifampicin (RIF) is one of the widely used anti-tubercular drugs (ATD). The present study discusses the development of biocompatible nanoparticle-RIF complexes with superior inhibitory activity against both Mycobacterium smegmatis (M. smegmatis) and Mycobacterium tuberculosis (M. tuberculosis). Iron oxide nanoparticles (NPs) synthesized by gas phase condensation and NP-RIF complexes were tested against M. smegmatis SN2 strain as well as M. tuberculosis H37Rv laboratory strain. These complexes showed significantly better inhibition of M. smegmatis SN2 strain at a much lower effective concentration (27.5 μg ml-1) as compared to neat RIF (125 μg ml-1). Similarly M. tuberculosis H37Rv laboratory strain was susceptible to both nanoparticle-RIF complex and neat RIF at a minimum inhibitory concentration of 0.22 and 1 μg ml-1, respectively. Further studies are underway to determine the efficacy of NPs-RIF complexes in clinical isolates of M. tuberculosis as well as MDR isolates.

  4. Inhibition of autophagy enhances the anticancer activity of silver nanoparticles

    PubMed Central

    Lin, Jun; Huang, Zhihai; Wu, Hao; Zhou, Wei; Jin, Peipei; Wei, Pengfei; Zhang, Yunjiao; Zheng, Fang; Zhang, Jiqian; Xu, Jing; Hu, Yi; Wang, Yanhong; Li, Yajuan; Gu, Ning; Wen, Longping

    2014-01-01

    Silver nanoparticles (Ag NPs) are cytotoxic to cancer cells and possess excellent potential as an antitumor agent. A variety of nanoparticles have been shown to induce autophagy, a critical cellular degradation process, and the elevated autophagy in most of these situations promotes cell death. Whether Ag NPs can induce autophagy and how it might affect the anticancer activity of Ag NPs has not been reported. Here we show that Ag NPs induced autophagy in cancer cells by activating the PtdIns3K signaling pathway. The autophagy induced by Ag NPs was characterized by enhanced autophagosome formation, normal cargo degradation, and no disruption of lysosomal function. Consistent with these properties, the autophagy induced by Ag NPs promoted cell survival, as inhibition of autophagy by either chemical inhibitors or ATG5 siRNA enhanced Ag NPs-elicited cancer cell killing. We further demonstrated that wortmannin, a widely used inhibitor of autophagy, significantly enhanced the antitumor effect of Ag NPs in the B16 mouse melanoma cell model. Our results revealed a novel biological activity of Ag NPs in inducing cytoprotective autophagy, and inhibition of autophagy may be a useful strategy for improving the efficacy of Ag NPs in anticancer therapy. PMID:25484080

  5. Inhibition of autophagy enhances the anticancer activity of silver nanoparticles.

    PubMed

    Lin, Jun; Huang, Zhihai; Wu, Hao; Zhou, Wei; Jin, Peipei; Wei, Pengfei; Zhang, Yunjiao; Zheng, Fang; Zhang, Jiqian; Xu, Jing; Hu, Yi; Wang, Yanhong; Li, Yajuan; Gu, Ning; Wen, Longping

    2014-01-01

    Silver nanoparticles (Ag NPs) are cytotoxic to cancer cells and possess excellent potential as an antitumor agent. A variety of nanoparticles have been shown to induce autophagy, a critical cellular degradation process, and the elevated autophagy in most of these situations promotes cell death. Whether Ag NPs can induce autophagy and how it might affect the anticancer activity of Ag NPs has not been reported. Here we show that Ag NPs induced autophagy in cancer cells by activating the PtdIns3K signaling pathway. The autophagy induced by Ag NPs was characterized by enhanced autophagosome formation, normal cargo degradation, and no disruption of lysosomal function. Consistent with these properties, the autophagy induced by Ag NPs promoted cell survival, as inhibition of autophagy by either chemical inhibitors or ATG5 siRNA enhanced Ag NPs-elicited cancer cell killing. We further demonstrated that wortmannin, a widely used inhibitor of autophagy, significantly enhanced the antitumor effect of Ag NPs in the B16 mouse melanoma cell model. Our results revealed a novel biological activity of Ag NPs in inducing cytoprotective autophagy, and inhibition of autophagy may be a useful strategy for improving the efficacy of Ag NPs in anticancer therapy. PMID:25484080

  6. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

    PubMed Central

    Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

    2014-01-01

    To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells. PMID:24591829

  7. Curcuma Contra Cancer? Curcumin and Hodgkin’s Lymphoma

    PubMed Central

    Kewitz, Stefanie; Volkmer, Ines; Staege, Martin S.

    2013-01-01

    Curcumin, a phytochemical isolated from curcuma plants which are used as coloring ingredient for the preparation of curry powder, has several activities which suggest that it might be an interesting drug for the treatment or prevention of cancer. Curcumin targets different pathways which are involved in the malignant phenotype of tumor cells, including the nuclear factor kappa B (NFKB) pathway. This pathway is deregulated in multiple tumor entities, including Hodgkin’s lymphoma (HL). Indeed, curcumin can inhibit growth of HL cell lines and increases the sensitivity of these cells for cisplatin. In this review we summarize curcumin activities with special focus on possible activities against HL cells. PMID:24665206

  8. Curcumin inhibits anchorage-independent growth of HT29 human colon cancer cells by targeting epigenetic restoration of the tumor suppressor gene DLEC1

    PubMed Central

    Guo, Yue; Shu, Limin; Zhang, Chengyue; Su, Zheng-Yuan; Kong, Ah-Ng Tony

    2015-01-01

    Colorectal cancer remains the most prevalent malignancy in humans. The impact of epigenetic alterations on the development of this complex disease is now being recognized. The dynamic and reversible nature of epigenetic modifications makes them a promising target in colorectal cancer chemoprevention and treatment. Curcumin (CUR), the major component in Curcuma longa, has been shown as a potent chemopreventive phytochemical that modulates various signaling pathways. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene with reduced transcriptional activity and promoter hypermethylation in various cancers, including colorectal cancer. In the present study, we aimed to investigate the inhibitory role of DLEC1 in anchorage-independent growth of the human colorectal adenocarcinoma HT29 cells and epigenetic regulation by CUR. Specifically, we found that CUR treatment inhibited colony formation of HT29 cells, whereas stable knockdown of DLEC1 using lentiviral short hairpin RNA vector increased cell proliferation and colony formation. Knockdown of DLEC1 in HT29 cells attenuated the ability of CUR to inhibit anchorage-independent growth. Methylation-specific polymerase chain reaction (MSP), bisulfite genomic sequencing, and methylated DNA immunoprecipitation revealed that CUR decreased CpG methylation of the DLEC1 promoter in HT29 cells after 5 days of treatment, corresponding to increased mRNA expression of DLEC1. Furthermore, CUR decreased the protein expression of DNA methyltransferases and subtypes of histone deacetylases (HDAC4, 5, 6, and 8). Taken together, our results suggest that the inhibitory effect of CUR on anchorage-independent growth of HT29 cells could, at least in part, involve the epigenetic demethylation and up-regulation of DLEC1. PMID:25640947

  9. The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity

    PubMed Central

    2010-01-01

    Background We characterized the biologic effects of a novel small molecule STAT3 pathway inhibitor that is derived from the natural product curcumin. We hypothesized this lead compound would specifically inhibit the STAT3 signaling pathway to induce apoptosis in melanoma cells. Results FLLL32 specifically reduced STAT3 phosphorylation at Tyr705 (pSTAT3) and induced apoptosis at micromolar amounts in human melanoma cell lines and primary melanoma cultures as determined by annexin V/propidium iodide staining and immunoblot analysis. FLLL32 treatment reduced expression of STAT3-target genes, induced caspase-dependent apoptosis, and reduced mitochondrial membrane potential. FLLL32 displayed specificity for STAT3 over other homologous STAT proteins. In contrast to other STAT3 pathway inhibitors (WP1066, JSI-124, Stattic), FLLL32 did not abrogate IFN-γ-induced pSTAT1 or downstream STAT1-mediated gene expression as determined by Real Time PCR. In addition, FLLL32 did not adversely affect the function or viability of immune cells from normal donors. In peripheral blood mononuclear cells (PBMCs), FLLL32 inhibited IL-6-induced pSTAT3 but did not reduce signaling in response to immunostimulatory cytokines (IFN-γ, IL 2). Treatment of PBMCs or natural killer (NK) cells with FLLL32 also did not decrease viability or granzyme b and IFN-γ production when cultured with K562 targets as compared to vehicle (DMSO). Conclusions These data suggest that FLLL32 represents a lead compound that could serve as a platform for further optimization to develop improved STAT3 specific inhibitors for melanoma therapy. PMID:20576164

  10. Combination of Tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species

    PubMed Central

    Sankpal, Umesh T.; Nagaraju, Ganji Purnachandra; Gottipolu, Sriharika R.; Hurtado, Myrna; Jordan, Christopher G.; Simecka, Jerry W.; Shoji, Mamoru; El-Rayes, Bassel; Basha, Riyaz

    2016-01-01

    Curcumin (Cur) has been extensively studied in several types of malignancies including colorectal cancer (CRC); however its clinical application is greatly affected by low bioavailability. Several strategies to improve the therapeutic response of Cur are being pursued, including its combination with small molecules and drugs. We investigated the therapeutic efficacy of Cur in combination with the small molecule tolfenamic acid (TA) in CRC cell lines. TA has been shown to inhibit the growth of human cancer cells in vitro and in vivo, via targeting the transcription factor specificity protein1 (Sp1) and suppressing survivin expression. CRC cell lines HCT116 and HT29 were treated with TA and/or Cur and cell viability was measured 24–72 hours post-treatment. While both agents caused a steady reduction in cell viability, following a clear dose/time-dependent response, the combination of TA+Cur showed higher growth inhibition when compared to either single agent. Effects on apoptosis were determined using flow cytometry (JC-1 staining to measure mitochondrial membrane potential), Western blot analysis (c-PARP expression) and caspase 3/7 activity. Reactive oxygen species (ROS) levels were measured by flow cytometry and the translocation of NF-kB into the nucleus was determined using immunofluorescence. Results showed that apoptotic markers and ROS activity were significantly upregulated following combination treatment, when compared to the individual agents. This was accompanied by decreased expression of Sp1, survivin and NF-kB translocation. The combination of TA+Cur was more effective in HCT116 cells than HT29 cells. These results demonstrate that TA may enhance the anti-proliferative efficacy of Cur in CRC cells. PMID:26672603

  11. Induction of oxidative stress and inhibition of superoxide dismutase expression in rat cerebral cortex and cerebellum by PTU-induced hypothyroidism and its reversal by curcumin.

    PubMed

    Jena, Srikanta; Anand, Chinmay; Chainy, Gagan Bihari Nityananda; Dandapat, Jagneshwar

    2012-08-01

    The present study was carried out to elucidate the effectiveness of curcumin in ameliorating the expression of superoxide dismutase (SOD) in cerebral cortex and cerebellum of rat brain under 6-propyl-2-thiouracil (PTU)-induced hypothyroidism. Induction of hypothyroidism in adult rats by PTU resulted in augmentation of lipid peroxidation (LPx), an index of oxidative stress in cerebellum but not in cerebral cortex. Curcumin-supplementation to PTU-treated (hypothyroid) rats showed significant reduction in the level of LPx in both the regions of brain. The decreased translated products (SOD1 and SOD2) and the unchanged activity of SOD in cerebral cortex of PTU-treated rats were increased on supplementation of curcumin to the hypothyroid rats. Declined translated products of SOD1 and SOD2 in cerebellum of PTU-treated rats were alleviated on administration of curcumin to hypothyroid rats. On the other hand, the decreased activity of SOD in cerebellum of PTU-treated rats was further declined on administration of curcumin to the hypothyroid rats. Results of the present investigation indicate that curcumin differentially modulates the expression of superoxide dismutase in rat brain cortex and cerebellum under PTU-induced hypothyroidism. PMID:22076484

  12. Curcumin and aging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Curcumin has been used commonly as a spice, food additive, and an herbal medicine worldwide. Known as a bioactive polyphenolic, curcumin has a broad range of beneficial properties to human health. Recently, active research on curcumin with respect to aging and related traits in model organisms has d...

  13. Antimicrobial activity of curcumin-loaded myristic acid microemulsions against Staphylococcus epidermidis.

    PubMed

    Liu, Chi-Hsien; Huang, Hsin-Ying

    2012-01-01

    The bactericidal properties of myristic acid and curcumin were revealed in a number of studies. However, whether curcumin-loaded myristic acid microemulsions can be used to inhibit Staphylococcus epidermidis, which causes nosocomial infections, has not been reported. Our aim was to develop curcumin-loaded myristic acid microemulsions to inhibit S. epidermidis on the skin. The interfacial tension, size distribution, and viscosity data of the microemulsions were characterized to elucidate the physicochemical properties of the curcumin microemulsions. Curcumin distribution in neonate pig skin was visualized using confocal laser scanning microscopy. Dermal curcumin accumulation (326 µg/g skin) and transdermal curcumin penetration (87 µg/cm(2)/d) were obtained with the microemulsions developed herein. Curcumin at the concentration of 0.86 µg/mL in the myristic acid microemulsion could inhibit 50% of the bacterial growth, which was 12 times more effective than curcumin dissolved in dimethyl sulfoxide (DMSO). The cocktail combination of myristic acid and curcumin in the microemulsion carrier synergistically inhibited the growth of S. epidermidis. The results we obtained highlight the potential of using curcumin-loaded microemulsions as an alternative treatment for S. epidermidis-associated diseases and acne vulgaris. PMID:22976319

  14. Curcumin inhibits apoptosis by regulating intracellular calcium release, reactive oxygen species and mitochondrial depolarization levels in SH-SY5Y neuronal cells.

    PubMed

    Uğuz, Abdülhadi Cihangir; Öz, Ahmi; Nazıroğlu, Mustafa

    2016-08-01

    Neurological diseases such as Alzheimer's and Parkinson's diseases are incurable progressive neurological disorders caused by the degeneration of neuronal cells and characterized by motor and non-motor symptoms. Curcumin, a turmeric product, is an anti-inflammatory agent and an effective reactive oxygen and nitrogen species scavenging molecule. Hydrogen peroxide (H2O2) is the main source of oxidative stress, which is claimed to be the major source of neurological disorders. Hence, in this study we aimed to investigate the effect of curcumin on Ca(2+) signaling, oxidative stress parameters, mitochondrial depolarization levels and caspase-3 and -9 activities that are induced by the H2O2 model of oxidative stress in SH-SY5Y neuronal cells. SH-SY5Y neuronal cells were divided into four groups namely, the control, curcumin, H2O2, and curcumin + H2O2 groups. The dose and duration of curcumin and H2O2 were determined from published data. The cells in the curcumin, H2O2, and curcumin + H2O2 groups were incubated for 24 h with 5 µM curcumin and 100 µM H2O2. Lipid peroxidation and cytosolic free Ca(2+) concentrations were higher in the H2O2 group than in the control group; however, their levels were lower in the curcumin and curcumin + H2O2 groups than in the H2O2 group alone. Reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) values were lower in the H2O2 group although they were higher in the curcumin and curcumin + H2O2 groups than in the H2O2 group. Caspase-3 activity was lower in the curcumin group than in the H2O2 group. In conclusion, curcumin strongly induced modulator effects on oxidative stress, intracellular Ca(2+) levels, and the caspase-3 and -9 values in an experimental oxidative stress model in SH-SY5Y cells. PMID:26608462

  15. Copper oxide nanoparticles inhibit the metabolic activity of Saccharomyces cerevisiae.

    PubMed

    Mashock, Michael J; Kappell, Anthony D; Hallaj, Nadia; Hristova, Krassimira R

    2016-01-01

    Copper oxide nanoparticles (CuO NPs) are used increasingly in industrial applications and consumer products and thus may pose risk to human and environmental health. The interaction of CuO NPs with complex media and the impact on cell metabolism when exposed to sublethal concentrations are largely unknown. In the present study, the short-term effects of 2 different sized manufactured CuO NPs on metabolic activity of Saccharomyces cerevisiae were studied. The role of released Cu(2+) during dissolution of NPs in the growth media and the CuO nanostructure were considered. Characterization showed that the 28 nm and 64 nm CuO NPs used in the present study have different primary diameter, similar hydrodynamic diameter, and significantly different concentrations of dissolved Cu(2+) ions in the growth media released from the same initial NP mass. Exposures to CuO NPs or the released Cu(2+) fraction, at doses that do not have impact on cell viability, showed significant inhibition on S. cerevisiae cellular metabolic activity. A greater CuO NP effect on the metabolic activity of S. cerevisiae growth under respiring conditions was observed. Under the tested conditions the observed metabolic inhibition from the NPs was not explained fully by the released Cu ions from the dissolving NPs. PMID:26178758

  16. Fabrication of nanocomposite particles using a two-solution mixing-type spray nozzle for use in an inhaled curcumin formulation.

    PubMed

    Taki, Moeko; Tagami, Tatsuaki; Fukushige, Kaori; Ozeki, Tetsuya

    2016-09-10

    A unique two-solution mixing-type spray nozzle is useful for producing nanocomposite particles (microparticles containing drug nanoparticles) in one step. The nanocomposite particles can prevent nanoparticle aggregation. Curcumin has many reported pharmacological effects. Curcumin was entrapped in mannitol microparticles using a spray dryer coupled with a two-solution mixing-type spray nozzle to prepare "curcumin nanocomposite particles" and the application of these particles for inhalation formulations was investigated. Spray drying conditions (flow rate, concentration and inlet temperature) affected the size of both the resulting curcumin nanocomposite particles and the curcumin nanoparticles in the nanocomposite particles. The aerosol performance of the curcumin nanocomposite particles changed depending on the spray drying conditions and several conditions provided better deposition compared with the curcumin original powder. The curcumin nanocomposite particles showed an improved dissolution profile of curcumin compared with the original powder. Furthermore, the curcumin nanocomposite particles showed a higher cytotoxic effect compared with the curcumin original powder towards three cancer cell lines. Curcumin nanocomposite particles containing curcumin nanoparticles show promise as an inhalation formulation for treating lung-related diseases including cancer. PMID:27374204

  17. The chemistry of curcumin: from extraction to therapeutic agent.

    PubMed

    Priyadarsini, Kavirayani Indira

    2014-01-01

    Curcumin, a pigment from turmeric, is one of the very few promising natural products that has been extensively investigated by researchers from both the biological and chemical point of view. While there are several reviews on the biological and pharmacological effects of curcumin, chemistry reviews are comparatively scarcer. In this article, an overview of different aspects of the unique chemistry research on curcumin will be discussed. These include methods for the extraction from turmeric, laboratory synthesis methods, chemical and photochemical degradation and the chemistry behind its metabolism. Additionally other chemical reactions that have biological relevance like nucleophilic addition reactions, and metal chelation will be discussed. Recent advances in the preparation of new curcumin nanoconjugates with metal and metal oxide nanoparticles will also be mentioned. Directions for future investigations to be undertaken in the chemistry of curcumin have also been suggested. PMID:25470276

  18. Photo-induced green synthesis and antimicrobial efficacy of poly (ɛ-caprolactone)/curcumin/grape leaf extract-silver hybrid nanoparticles.

    PubMed

    El-Sherbiny, Ibrahim M; El-Shibiny, Ayman; Salih, Ehab

    2016-07-01

    This study reports the photo-induced green synthesis and antimicrobial assessment of poly(ɛ-caprolactone)/curcumin/grape leaf extract-Ag hybrid nanoparticles (PCL/Cur/GLE-Ag NPs). PCL/Cur/GLE NPs were synthesized via emulsion-solvent evaporation in the presence of PVA as a capping agent, then used as active nano-supports for the green synthesis and stabilization of AgNPs on their surfaces. Both Cur and GLE were selected and incorporated into the PCL nano-supports due to their reported promising antimicrobial activity that would further enhance that of the synthesized AgNPs. The developed PCL/Cur/GLE NPs and PCL/Cur/GLE-Ag hybrid NPs were characterized using UV-visible spectrophotometry, high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). HRTEM images showed that the PCL/Cur/GLE NPs are monodispersed and spherical with size of about 270nm, and the AgNPs were formed mainly on their surfaces with average size in the range 10-30nm. The synthesized AgNPs were found to be crystalline as shown by XRD patterns with fcc phase oriented along the (111), (200), (220) and (311) planes. The antimicrobial characteristics of the newly developed NPs were investigated against gram-positive and gram-negative bacteria in addition to two fungal strains. The results demonstrated that the PCL/Cur/GLE-Ag hybrid NPs have a potential antimicrobial activity against pathogenic bacterial species and could be considered as an alternative antibacterial agent. PMID:27183490

  19. Folic acid functionalized long-circulating co-encapsulated docetaxel and curcumin solid lipid nanoparticles: In vitro evaluation, pharmacokinetic and biodistribution in rats.

    PubMed

    Pawar, Harish; Surapaneni, Sunil Kumar; Tikoo, Kulbhushan; Singh, Charan; Burman, Rohani; Gill, Manjinder Singh; Suresh, Sarasija

    2016-05-01

    The purpose of this study was to develop folic acid functionalized long-circulating co-encapsulated docetaxel (DTX) and curcumin (CRM) solid lipid nanoparticles (F-DC-SLN) to improve the pharmacokinetic and efficacy of DTX therapy. F-DC-SLN was prepared by hot melt-emulsification method and optimized by face centered-central composite design (FC-CCD). The SLN was characterized in terms of size and size distribution, drug entrapment efficiency and release profile. The cytotoxicity and cell uptake of the SLN formulations were evaluated in MCF-7 and MDA-MB-231 cell lines. The in vivo pharmacokinetic and biodistribution were studied in Wistar rats. F-DC-SLN exhibited 247.5 ± 3.40 nm particle size with 73.88 ± 1.08% entrapment efficiency and zeta potential of 14.53 ± 3.6 mV. Transmission electron microscopy (TEM) revealed spherical morphology of the SLN. Fluorescence microscopy confirmed the targeting efficacy of F-DC-SLN in MCF-7 cells. F-DC-SLN exhibited a significant increase in area under the curve (594.21 ± 64.34 versus 39.05 ± 7.41 μg/mL h) and mean residence time (31.14 ± 19.94 versus 7.24 ± 4.51 h) in comparison to Taxotere®. In addition, decreased DTX accumulation from F-DC-SLN in the heart and kidney in comparison to Taxotere may avoid to toxicity these vital organs. In conclusion, the F-DC-SLN improved the efficacy and pharmacokinetic profile of DTX exhibiting enhanced potential in optimizing breast cancer therapy. PMID:26878325

  20. Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice

    PubMed Central

    Thakkar, Arvind; Chenreddy, Sushma; Thio, Astrid; Khamas, Wael; Wang, Jeffrey; Prabhu, Sunil

    2016-01-01

    Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer. PMID:27499621

  1. Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice.

    PubMed

    Thakkar, Arvind; Chenreddy, Sushma; Thio, Astrid; Khamas, Wael; Wang, Jeffrey; Prabhu, Sunil

    2016-01-01

    Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer. PMID:27499621

  2. Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia

    SciTech Connect

    Rajasingh, Johnson; Raikwar, Himanshu P.; Muthian, Gladson; Johnson, Caroline; Bright, John J. . E-mail: jbright1@clarian.org

    2006-02-10

    Adult T cell leukemia is an aggressive and frequently fatal malignancy that expressess constitutively activated growth-signaling pathways in association with deregulated growth and resistance to apoptosis. Curcumin (diferuloylmethane) is a naturally occurring yellow pigment, isolated from the rhizomes of the plant Curcuma longa that has traditionally been used in the treatment of injury and inflammation. But the effect and mechanism of action of curcumin on T cell leukemia is not known. To investigate the antitumor activity of curcumin in T cell leukemia, we examined its effect on constitutive phosphorylation of JAK and STAT proteins, proliferation, and apoptosis in HTLV-I-transformed T cell lines. HTLV-I-transformed T cell leukemia lines, MT-2, HuT-102, and SLB-1, express constitutively phosphorylated JAK3, TYK2, STAT3, and STAT5 signaling proteins. In vitro treatment with curcumin induced a dose-dependent decrease in JAK and STAT phosphorylation resulting in the induction of growth-arrest and apoptosis in T cell leukemia. The induction of growth-arrest and apoptosis in association with the blockade of constitutively active JAK-STAT pathway suggests this be a mechanism by which curcumin induces antitumor activity in T cell leukemia.

  3. Novel delivery system for natural products: Nano-curcumin formulations

    PubMed Central

    Rahimi, Hamid Reza; Nedaeinia, Reza; Sepehri Shamloo, Alireza; Nikdoust, Shima; Kazemi Oskuee, Reza

    2016-01-01

    Objective: Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. Curcumin molecules have special intrinsic features that can target the intracellular enzymes, genome (DNA) and messengers (RNA). A wide range of studies have been conducted on the physicochemical traits and pharmacological effects of curcumin on different diseases like cardiovascular diseases, diabetes, cancer, rheumatoid arthritis, Alzheimer’s, inflammatory bowel disease (IBD), and even it has wound healing. Oral bioavailability of curcumin is rather poor, which would certainly put some boundaries in the employment of this drug. Materials and Methods: Bibliographical searches were performed using MEDLINE/ScienceDirect/OVID up to February 2015 using the following keywords (all fields): (“Curcumin” OR “Curcuma longa”) AND [(nanoparticles) OR (Nanomicelles) OR (micro emulsions) OR (liposome) OR (phospholipid). Results: Consequently, for any developments of curcumin in the future, analogues of curcumin that have better bioavailability or substitute formulations are needed crucially. Conclusion: These studies indicated that nanotechnology can formulate curcumin effectively, and this nano-formulated curcumin with a potent ability against various cancer cells, were represented to have better efficacy and bioavailability under in vivo conditions. PMID:27516979

  4. A magnetically drivable nanovehicle for curcumin with antioxidant capacity and MRI relaxation properties.

    PubMed

    Magro, Massimiliano; Campos, René; Baratella, Davide; Lima, Giuseppina; Holà, Katerina; Divoky, Clemens; Stollberger, Rudolf; Malina, Ondrej; Aparicio, Claudia; Zoppellaro, Giorgio; Zbořil, Radek; Vianello, Fabio

    2014-09-01

    Curcumin possesses wide-ranging anti-inflammatory and anti-cancer properties and its biological activity can be linked to its potent antioxidant capacity. Superparamagnetic maghemite (γ-Fe2 O3 ), called surface-active maghemite nanoparticles (SAMNs) were surface-modified with curcumin molecules, due to the presence of under-coordinated Fe(III) atoms on the nanoparticle surface. The so-obtained curcumin-modified SAMNs (SAMN@curcumin) had a mean size of 13±4 nm. SAMN@curcumin was characterized by transmission and scanning electron microscopy, UV/Vis, FTIR, and Mössbauer spectroscopy, X-ray powder diffraction, bulk susceptibility (SQUID), and relaxometry measurements (MRI imaging). The high negative contrast proclivity of SAMN@curcumin to act as potential contrast agent in MRI screenings was also tested. Moreover, the redox properties of bound curcumin were probed by electrochemistry. SAMN@curcumin was studied in the presence of different electroactive molecules, namely hydroquinone, NADH and ferrocyanide, to assess its redox behavior. Finally, SAMN@curcumin was electrochemically probed in the presence of hydrogen peroxide, demonstrating the stability and reactivity of bound curcumin. PMID:25079005

  5. Comparison of pharmaceutical nanoformulations for curcumin: Enhancement of aqueous solubility and carrier retention.

    PubMed

    Allijn, Iris E; Schiffelers, Raymond M; Storm, Gert

    2016-06-15

    Curcumin, originally used in traditional medicine and as a spice, is one of the most studied and most popular natural products of the past decade. It has been described to be an effective anti-inflammatory and anti-cancer drug and protects against chronic diseases such as rheumatoid arthritis and atherosclerosis. Despite these promising pharmacological properties, curcumin is also very lipophilic, which makes its formulation challenging. Ideally the nanocarrier should additionally also retain the encapsulated curcumin to provide target tissue accumulation. In this study we aimed to tackle this aqueous solubility and carrier retention challenge of curcumin by encapsulating curcumin in different nanoparticles. We successfully loaded LDL (30nm), polymeric micelles (80nm), liposomes (180nm) and Intralipid (280nm) with curcumin. The relative loading capacity was inversely related to the size of the particle. The stability for all formulations was determined in fetal bovine serum over a course of 24h. Although all curcumin-nanoparticles were stable in buffer solution, all leaked more than 70% of curcumin under physiological conditions. Altogether, tested nanoparticles do solve the aqueous insolubility problem of curcumin, however, because of their leaky nature, the challenge of carrier retention remains. PMID:27139142

  6. Synergistic Effect of Functionalized Nickel Nanoparticles and Quercetin on Inhibition of the SMMC-7721 Cells Proliferation

    NASA Astrophysics Data System (ADS)

    Guo, Dadong; Wu, Chunhui; Li, Jingyuan; Guo, Airong; Li, Qingning; Jiang, Hui; Chen, Baoan; Wang, Xuemei

    2009-12-01

    The effect of functionalized nickel (Ni) nanoparticles capped with positively charged tetraheptylammonium on cellular uptake of drug quercetin into hepatocellular carcinoma cells (SMMC-7721) has been explored in this study via microscopy and electrochemical characterization as well as MTT assay. Meanwhile, the influence of Ni nanoparticles and/or quercetin on cell proliferation has been further evaluated by the real-time cell electronic sensing (RT-CES) study. Our observations indicate that Ni nanoparticles could efficiently improve the permeability of cancer cell membrane, and remarkably enhance the accumulation of quercetin in SMMC-7721 cells, suggesting that Ni nanoparticles and quercetin would facilitate the synergistic effect on inhibiting proliferation of cancer cells.

  7. Inhibition Effects of Silver Nanoparticles against Powdery Mildews on Cucumber and Pumpkin.

    PubMed

    Lamsal, Kabir; Kim, Sang-Woo; Jung, Jin Hee; Kim, Yun Seok; Kim, Kyoung Su; Lee, Youn Su

    2011-03-01

    Powdery mildew is one of the most devastating diseases in cucurbits. Crop yield can decline as the disease severity increases. In this study, we evaluated the effect of silver nanoparticles against powdery mildew under different cultivation conditions in vitro and in vivo . Silver nanoparticles (WA-CV-WA13B) at various concentrations were applied before and after disease outbreak in plants to determine antifungal activities. In the field tests, the application of 100 ppm silver nanoparticles showed the highest inhibition rate for both before and after the outbreak of disease on cucumbers and pumpkins. Also, the application of 100 ppm silver nanoparticles showed maximum inhibition for the growth of fungal hyphae and conidial germination in in vivo tests. Scanning electron microscope results indicated that the silver nanoparticles caused detrimental effects on both mycelial growth and conidial germination. PMID:22783069

  8. Curcumin Reduces Amyloid Fibrillation of Prion Protein and Decreases Reactive Oxidative Stress

    PubMed Central

    Lin, Chi-Fen; Yu, Kun-Hua; Jheng, Cheng-Ping; Chung, Raymond; Lee, Cheng-I

    2013-01-01

    Misfolding and aggregation into amyloids of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. Various studies on curcumin demonstrate promise for the prevention of Alzheimer’s disease and inhibition of PrPres accumulation. To evaluate the effect of curcumin on amyloid fibrillation of prion protein, we first investigated the effect of curcumin on mouse prion protein (mPrP) in a cell-free system. Curcumin reduced the prion fibril formation significantly. Furthermore, we monitored the change in apoptosis and reactive oxygen species (ROS) level upon curcumin treatment in mouse neuroblastoma cells (N2a). Curcumin effectively rescues the cells from apoptosis and decreases the ROS level caused by subsequent co-incubation with prion amyloid fibrils. The assays in cell-free mPrP and in N2a cells of this work verified the promising effect of curcumin on the prevention of transmissible neurodegenerative diseases. PMID:25437204

  9. Effect of Curcumin Against Proteus mirabilis During Crystallization of Struvite from Artificial Urine.

    PubMed

    Prywer, Jolanta; Torzewska, Agnieszka

    2012-01-01

    We investigated the activity of curcumin against Proteus mirabilis and the struvite crystallization in relation to urinary stones formation. In order to evaluate an activity of curcumin we performed an in vitro experiment of struvite growth from artificial urine. The crystallization process was induced by Proteus mirabilis to mimic the real urinary tract infection, which usually leads to urinary stone formation. The results demonstrate that curcumin exhibits the effect against Proteus mirabilis inhibiting the activity of urease-an enzyme produced by these microorganisms. Addition of curcumin increases the induction time and decreases the efficiency of growth of struvite compared with the absence of curcumin. Interestingly, the addition of curcumin does not affect the crystal morphology and habit. In conclusion, curcumin has demonstrated its significant potential to be further investigated for its use in the case of struvite crystallization induced for the growth by Proteus mirabilis in relation to urinary stone formation. PMID:21808656

  10. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Gou, Maling; Men, Ke; Shi, Huashan; Xiang, Mingli; Zhang, Juan; Song, Jia; Long, Jianlin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, Zhiyong

    2011-04-01

    Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 +/- 0.011) with a mean particle size of 27.3 +/- 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 +/- 1.02%, and drug loading of 12.95 +/- 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t1/2 and AUC of curcuminin vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesisin vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cellsin vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg-1curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

  11. Synergistic effects of curcumin and bevacizumab on cell signaling pathways in hepatocellular carcinoma.

    PubMed

    Gao, Jian-Zhi; DU, Jing-Li; Wang, Yong-Ling; Li, Jia; Wei, Li-Xin; Guo, Ming-Zhou

    2015-01-01

    The aim of the present study was to explore the effects of curcumin in combination with bevacizumab on the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)/K-ras pathway in hepatocellular carcinoma. A total of 30 Sprague Dawley (SD) rats were randomly divided into five groups: Control, model, curcumin, VEGF blocker, and curcumin + VEGF blocker groups. The mRNA levels of VEGF and VEGFR in all groups were subsequently measured by quantitative reverse transcriptase-polymerase chain reaction and the protein expression of K-ras was detected by western blot analysis. Compared with the control group, the mRNA levels of VEGF and VEGFR were revealed to be significantly increased in the model, curcumin and VEGF blocker groups. The VEGF mRNA levels in the curcumin, VEGF blocker and curcumin + VEGF blocker groups were all decreased when compared with the model group. In addition, the VEGF mRNA levels in the curcumin + VEGF blocker group were significantly lower compared with the curcumin group (P<0.05). The VEGF mRNA levels in the curcumin, VEGF blocker and curcumin + VEGF blocker groups were decreased when compared with the model group (P=0.0001). No significant differences in VEGF mRNA levels were identified between the VEGF blocker and curcumin groups (P=0.863), whereas the VEGF mRNA levels in the curcumin + VEGF blocker group were significantly lower than that of the curcumin group (P=0.025). Curcumin and the VEGF blocker are each capable of inhibiting hepatocellular carcinoma progression by regulating the VEGF/VEGFR/K-ras pathway. The combination of the two compounds has a synergistic effect on the inhibition of the effects of the VEGF signaling pathways in hepatocellular carcinoma progression. PMID:25435978

  12. Synergistic effects of curcumin and bevacizumab on cell signaling pathways in hepatocellular carcinoma

    PubMed Central

    GAO, JIAN-ZHI; DU, JING-LI; WANG, YONG-LING; LI, JIA; WEI, LI-XIN; GUO, MING-ZHOU

    2015-01-01

    The aim of the present study was to explore the effects of curcumin in combination with bevacizumab on the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)/K-ras pathway in hepatocellular carcinoma. A total of 30 Sprague Dawley (SD) rats were randomly divided into five groups: Control, model, curcumin, VEGF blocker, and curcumin + VEGF blocker groups. The mRNA levels of VEGF and VEGFR in all groups were subsequently measured by quantitative reverse transcriptase-polymerase chain reaction and the protein expression of K-ras was detected by western blot analysis. Compared with the control group, the mRNA levels of VEGF and VEGFR were revealed to be significantly increased in the model, curcumin and VEGF blocker groups. The VEGF mRNA levels in the curcumin, VEGF blocker and curcumin + VEGF blocker groups were all decreased when compared with the model group. In addition, the VEGF mRNA levels in the curcumin + VEGF blocker group were significantly lower compared with the curcumin group (P<0.05). The VEGF mRNA levels in the curcumin, VEGF blocker and curcumin + VEGF blocker groups were decreased when compared with the model group (P=0.0001). No significant differences in VEGF mRNA levels were identified between the VEGF blocker and curcumin groups (P=0.863), whereas the VEGF mRNA levels in the curcumin + VEGF blocker group were significantly lower than that of the curcumin group (P=0.025). Curcumin and the VEGF blocker are each capable of inhibiting hepatocellular carcinoma progression by regulating the VEGF/VEGFR/K-ras pathway. The combination of the two compounds has a synergistic effect on the inhibition of the effects of the VEGF signaling pathways in hepatocellular carcinoma progression. PMID:25435978

  13. Curcumin Resource Database.

    PubMed

    Kumar, Anil; Chetia, Hasnahana; Sharma, Swagata; Kabiraj, Debajyoti; Talukdar, Narayan Chandra; Bora, Utpal

    2015-01-01

    Curcumin is one of the most intensively studied diarylheptanoid, Curcuma longa being its principal producer. This apart, a class of promising curcumin analogs has been generated in laboratories, aptly named as Curcuminoids which are showing huge potential in the fields of medicine, food technology, etc. The lack of a universal source of data on curcumin as well as curcuminoids has been felt by the curcumin research community for long. Hence, in an attempt to address this stumbling block, we have developed Curcumin Resource Database (CRDB) that aims to perform as a gateway-cum-repository to access all relevant data and related information on curcumin and its analogs. Currently, this database encompasses 1186 curcumin analogs, 195 molecular targets, 9075 peer reviewed publications, 489 patents and 176 varieties of C. longa obtained by extensive data mining and careful curation from numerous sources. Each data entry is identified by a unique CRDB ID (identifier). Furnished with a user-friendly web interface and in-built search engine, CRDB provides well-curated and cross-referenced information that are hyperlinked with external sources. CRDB is expected to be highly useful to the researchers working on structure as well as ligand-based molecular design of curcumin analogs. PMID:26220923

  14. Curcumin Resource Database

    PubMed Central

    Kumar, Anil; Chetia, Hasnahana; Sharma, Swagata; Kabiraj, Debajyoti; Talukdar, Narayan Chandra; Bora, Utpal

    2015-01-01

    Curcumin is one of the most intensively studied diarylheptanoid, Curcuma longa being its principal producer. This apart, a class of promising curcumin analogs has been generated in laboratories, aptly named as Curcuminoids which are showing huge potential in the fields of medicine, food technology, etc. The lack of a universal source of data on curcumin as well as curcuminoids has been felt by the curcumin research community for long. Hence, in an attempt to address this stumbling block, we have developed Curcumin Resource Database (CRDB) that aims to perform as a gateway-cum-repository to access all relevant data and related information on curcumin and its analogs. Currently, this database encompasses 1186 curcumin analogs, 195 molecular targets, 9075 peer reviewed publications, 489 patents and 176 varieties of C. longa obtained by extensive data mining and careful curation from numerous sources. Each data entry is identified by a unique CRDB ID (identifier). Furnished with a user-friendly web interface and in-built search engine, CRDB provides well-curated and cross-referenced information that are hyperlinked with external sources. CRDB is expected to be highly useful to the researchers working on structure as well as ligand-based molecular design of curcumin analogs. Database URL: http://www.crdb.in PMID:26220923

  15. Food additives such as sodium sulphite, sodium benzoate and curcumin inhibit leptin release in lipopolysaccharide-treated murine adipocytes in vitro.

    PubMed

    Ciardi, Christian; Jenny, Marcel; Tschoner, Alexander; Ueberall, Florian; Patsch, Josef; Pedrini, Michael; Ebenbichler, Christoph; Fuchs, Dietmar

    2012-03-01

    Obesity leads to the activation of pro-inflammatory pathways, resulting in a state of low-grade inflammation. Recently, several studies have shown that the exposure to lipopolysaccharide (LPS) could initiate and maintain a chronic state of low-grade inflammation in obese people. As the daily intake of food additives has increased substantially, the aim of the present study was to investigate a potential influence of food additives on the release of leptin, IL-6 and nitrite in the presence of LPS in murine adipocytes. Leptin, IL-6 and nitrite concentrations were analysed in the supernatants of murine 3T3-L1 adipocytes after co-incubation with LPS and the food preservatives, sodium sulphite (SS), sodium benzoate (SB) and the spice and colourant, curcumin, for 24 h. In addition, the kinetics of leptin secretion was analysed. A significant and dose-dependent decrease in leptin was observed after incubating the cells with SB and curcumin for 12 and 24 h, whereas SS decreased leptin concentrations after 24 h of treatment. Moreover, SS increased, while curcumin decreased LPS-stimulated secretion of IL-6, whereas SB had no such effect. None of the compounds that were investigated influenced nitrite production. The food additives SS, SB and curcumin affect the leptin release after co-incubation with LPS from cultured adipocytes in a dose- and time-dependent manner. Decreased leptin release during the consumption of nutrition-derived food additives could decrease the amount of circulating leptin to which the central nervous system is exposed and may therefore contribute to an obesogenic environment. PMID:21801469

  16. Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo

    PubMed Central

    Grodzik, Marta; Sawosz, Ewa; Wierzbicki, Mateusz; Orlowski, Piotr; Hotowy, Anna; Niemiec, Tomasz; Szmidt, Maciej; Mitura, Katarzyna; Chwalibog, André

    2011-01-01

    The objective of the study was to determine the effect of carbon nanoparticles produced by different methods on the growth of brain tumor and the development of blood vessels. Glioblastoma multiforme cells were cultured on the chorioallantoic membrane of chicken embryo and after 7 days of incubation, were treated with carbon nanoparticles administered in ovo to the tumor. Both types of nanoparticles significantly decreased tumor mass and volume, and vessel area. Quantitative real-time polymerase chain reaction analysis showed downregulated fibroblast growth factor-2 and vascular endothelial growth factor expression at the messenger ribonucleic acid level. The present results demonstrate antiangiogenic activity of carbon nanoparticles, making them potential factors for anticancer therapy. PMID:22162660

  17. Conundrum and therapeutic potential of curcumin in drug delivery.

    PubMed

    Kumar, Anil; Ahuja, Alka; Ali, Javed; Baboota, Sanjula

    2010-01-01

    Turmeric, the source of the polyphenolic active compound curcumin (diferuloylmethane), has been used extensively in traditional medicine since ancient times as a household remedy against various diseases, including hepatic disorders, cough, sinusitis, rheumatism, and biliary disorders. In the past few decades, a number of studies have been done on curcumin showing its potential role in treating inflammatory disorders, cardiovascular disease, cancer, AIDS, and neurological disorders. However, the main drawback associated with curcumin is its poor aqueous solubility and stability in gastrointestinal fluids, which leads to poor bioavailability. Multifarious novel drug-delivery approaches, including microemulsions, nanoemulsions, liposomes, solid lipid nanoparticles, microspheres, solid dispersion, polymeric nanoparticles, and self-microemulsifying drug-delivery systems have been used to enhance the bioavailability and tissue-targeting ability of curcumin. These attempts have revealed promising results for enhanced bioavailability and targeting to disease such as cancer, but more extensive research on tissue-targeting and stability-related issues is needed. Tissue targeting and enhanced bioavailability of curcumin using novel drug-delivery methods with minimum side effects will in the near future bring this promising natural product to the forefront of therapy for the treatment of human diseases such as cancer and cardiovascular ailments. We provide a detailed analysis of prominent research in the field of curcumin drug delivery with special emphasis on bioavailability-enhancement approaches and novel drug-delivery system approaches. PMID:20932240

  18. Antimicrobial activity of curcumin against Helicobacter pylori isolates from India and during infections in mice.

    PubMed

    De, Ronita; Kundu, Parag; Swarnakar, Snehasikta; Ramamurthy, T; Chowdhury, Abhijit; Nair, G Balakrish; Mukhopadhyay, Asish K

    2009-04-01

    Treatment failure is a major cause of concern for the Helicobacter pylori-related gastroduodenal diseases like gastritis, peptic ulcer, and gastric cancer. Curcumin, diferuloylmethane from turmeric, has recently been shown to arrest H. pylori growth. The antibacterial activity of curcumin against 65 clinical isolates of H. pylori in vitro and during protection against H. pylori infection in vivo was examined. The MIC of curcumin ranges from 5 microg/ml to 50 microg/ml, showing its effectiveness in inhibiting H. pylori growth in vitro irrespective of the genetic makeup of the strains. The nucleotide sequences of the aroE genes, encoding shikimate dehydrogenase, against which curcumin seems to act as a noncompetitive inhibitor, from H. pylori strains presenting differential curcumin MICs showed that curcumin-mediated growth inhibition of Indian H. pylori strains may not be always dependent on the shikimate pathway. The antimicrobial effect of curcumin in H. pylori-infected C57BL/6 mice and its efficacy in reducing the gastric damage due to infection were examined histologically. Curcumin showed immense therapeutic potential against H. pylori infection as it was highly effective in eradication of H. pylori from infected mice as well as in restoration of H. pylori-induced gastric damage. This study provides novel insights into the therapeutic effect of curcumin against H. pylori infection, suggesting its potential as an alternative therapy, and opens the way for further studies on identification of novel antimicrobial targets of curcumin. PMID:19204190

  19. Design and In Vitro Evaluation of a New Nano-Microparticulate System for Enhanced Aqueous-Phase Solubility of Curcumin

    PubMed Central

    Guzman-Villanueva, Diana; El-Sherbiny, Ibrahim M.; Herrera-Ruiz, Dea; Smyth, Hugh D. C.

    2013-01-01

    Curcumin, a yellow polyphenol derived from the turmeric Curcuma longa, has been associated with a diverse therapeutic potential including anti-inflammatory, antioxidant, antiviral, and anticancer properties. However, the poor aqueous solubility and low bioavailability of curcumin have limited its potential when administrated orally. In this study, curcumin was encapsulated in a series of novel nano-microparticulate systems developed to improve its aqueous solubility and stability. The nano-microparticulate systems are based entirely on biocompatible, biodegradable, and edible polymers including chitosan, alginate, and carrageenan. The particles were synthesized via ionotropic gelation. Encapsulating the curcumin into the hydrogel nanoparticles yielded a homogenous curcumin dispersion in aqueous solution compared to the free form of curcumin. Also, the in vitro release profile showed up to 95% release of curcumin from the developed nano-microparticulate systems after 9 hours in PBS at pH 7.4 when freeze-dried particles were used. PMID:23984402

  20. Nanoparticles of Selaginella doederleinii leaf extract inhibit human lung cancer cells A549

    NASA Astrophysics Data System (ADS)

    Syaefudin; Juniarti, A.; Rosiyana, L.; Setyani, A.; Khodijah, S.

    2016-01-01

    The aim of the present study is to evaluate cytotoxicity effect of nanoparticles of Selaginella doederleinii (S. doederleinii) leaves extract. S. doederleinii was extracted by maceration method using 70%(v/v) ethanol as solvent. Phytochemical content was analyzed qualitatively by using Harborne and Thin Layer Chromatography (TLC) methods. Nanoparticle extract was prepared by ionic gelation using chitosan as encapsulant agent. Anticancer activity was performed by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results showed that S. doederleinii contains of flavonoids. Nanoparticle of S. doederleinii leaves extract greatly inhibited A549 cells growth (cancer cells), with IC50 of 3% or 1020 μg/ml. These nanoparticles extract also inhibited the growth of Chang cells (normal cells), with IC50 of 4% or 1442 μg/ml. The effective concentration of nanoparticles extract which inhibits cancer cells without harming the normal cells is 0.5% or 167 μg/ml. Further studies are needed to obtain the concentration of nanoparticles extract which can selectively suppress cancer cells.

  1. In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles

    SciTech Connect

    Park, Margriet V.D.Z. Annema, Wijtske; Salvati, Anna; Lesniak, Anna; Elsaesser, Andreas; Barnes, Clifford; McKerr, George; Howard, C. Vyvyan; Lynch, Iseult; Dawson, Kenneth A.; Piersma, Aldert H.; Jong, Wim H. de

    2009-10-01

    While research into the potential toxic properties of nanomaterials is now increasing, the area of developmental toxicity has remained relatively uninvestigated. The embryonic stem cell test is an in vitro screening assay used to investigate the embryotoxic potential of chemicals by determining their ability to inhibit differentiation of embryonic stem cells into spontaneously contracting cardiomyocytes. Four well characterized silica nanoparticles of various sizes were used to investigate whether nanomaterials are capable of inhibition of differentiation in the embryonic stem cell test. Nanoparticle size distributions and dispersion characteristics were determined before and during incubation in the stem cell culture medium by means of transmission electron microscopy (TEM) and dynamic light scattering. Mouse embryonic stem cells were exposed to silica nanoparticles at concentrations ranging from 1 to 100 {mu}g/ml. The embryonic stem cell test detected a concentration dependent inhibition of differentiation of stem cells into contracting cardiomyocytes by two silica nanoparticles of primary size 10 (TEM 11) and 30 (TEM 34) nm while two other particles of primary size 80 (TEM 34) and 400 (TEM 248) nm had no effect up to the highest concentration tested. Inhibition of differentiation of stem cells occurred below cytotoxic concentrations, indicating a specific effect of the particles on the differentiation of the embryonic stem cells. The impaired differentiation of stem cells by such widely used particles warrants further investigation into the potential of these nanoparticles to migrate into the uterus, placenta and embryo and their possible effects on embryogenesis.

  2. Engineered polymer nanoparticles containing hydrophobic dipeptide for inhibition of amyloid-β fibrillation.

    PubMed

    Skaat, Hadas; Chen, Ravit; Grinberg, Igor; Margel, Shlomo

    2012-09-10

    Protein aggregation into amyloid fibrils is implicated in the pathogenesis of many neurodegenerative diseases. Engineered nanoparticles have emerged as a potential approach to alter the kinetics of protein fibrillation process. Yet, there are only a few reports describing the use of nanoparticles for inhibition of amyloid-β 40 (Aβ(40)) peptide aggregation, involved in Alzheimer's disease (AD). In the present study, we designed new uniform biocompatible amino-acid-based polymer nanoparticles containing hydrophobic dipeptides in the polymer side chains. The dipeptide residues were designed similarly to the hydrophobic core sequence of Aβ. Poly(N-acryloyl-L-phenylalanyl-L-phenylalanine methyl ester) (polyA-FF-ME) nanoparticles of 57 ± 6 nm were synthesized by dispersion polymerization of the monomer A-FF-ME in 2-methoxy ethanol, followed by precipitation of the obtained polymer in aqueous solution. Cell viability assay confirmed that no significant cytotoxic effect of the polyA-FF-ME nanoparticles on different human cell lines, e.g., PC-12 and SH-SY5Y, was observed. A significantly slow secondary structure transition from random coil to β-sheets during Aβ(40) fibril formation was observed in the presence of these nanoparticles, resulting in significant inhibition of Aβ(40) fibrillation kinetics. However, the polyA-FF-ME analogous nanoparticles containing the L-alanyl-L-alanine (AA) dipeptide in the polymer side groups, polyA-AA-ME nanoparticles, accelerate the Aβ(40) fibrillation kinetics. The polyA-FF-ME nanoparticles and the polyA-AA-ME nanoparticles may therefore contribute to a mechanistic understanding of the fibrillation process, leading to the development of therapeutic strategies against amyloid-related diseases. PMID:22897679

  3. Curcumin shows excellent therapeutic effect on psoriasis in mouse model.

    PubMed

    Kang, Di; Li, Bowen; Luo, Lei; Jiang, Wenbing; Lu, Qiumin; Rong, Mingqing; Lai, Ren

    2016-04-01

    Curcumin is an active herbal ingredient possessing surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. Recently, it has been reported to exhibit inhibitory activity on potassium channel subtype Kv1.3. As Kv1.3 channels are mainly expressed in T cells and play a key role in psoriasis, the effects of curcumin were investigated on inflammatory factors secretion in T cells and psoriasis developed in keratin (K) 14-vascular endothelial growth factor (VEGF) transgenic mouse model. Results showed that, 10 μM of curcumin significantly inhibited secretion of inflammatory factors including interleukin (IL)-17,IL-22, IFN-γ, IL-2, IL-8 and TNF-α in T cells by 30-60% in vitro. Notably, more than 50% of T cells proliferation was inhibited by application of 100 μM curcumin. Compared with severe psoriatic symptoms observed in the negative control mice, all psoriasis indexes including ear redness, weight, thickness and lymph node weight were significantly improved by oral application of curcumin in treatment mouse group. Histological examination indicated that curcumin had anti-inflammatory function in the experimental animals. More than 50% level of inflammatory factors including TNF-α, IFN-γ, IL-2, IL-12, IL-22 and IL-23 in mouse serum was decreased by curcumin treatment as well as cyclosporine. Compared with renal fibrosis observed in the mouse group treated by cyclosporine, no obvious side effect in mouse kidney was found after treated by curcumin. Taken together, curcumin, with high efficacy and safety, has a great potential to treat psoriasis. PMID:26826458

  4. Activation of microbubbles by low-intensity pulsed ultrasound enhances the cytotoxicity of curcumin involving apoptosis induction and cell motility inhibition in human breast cancer MDA-MB-231 cells.

    PubMed

    Li, Yixiang; Wang, Pan; Chen, Xiyang; Hu, Jianmin; Liu, Yichen; Wang, Xiaobing; Liu, Quanhong

    2016-11-01

    Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy. PMID:27245953

  5. Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells

    PubMed Central

    Montgomery, Amanda; Adeyeni, Temitope; San, KayKay; Heuertz, Rita M.; Ezekiel, Uthayashanker R.

    2016-01-01

    We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer. PMID:27390600

  6. Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells.

    PubMed

    Montgomery, Amanda; Adeyeni, Temitope; San, KayKay; Heuertz, Rita M; Ezekiel, Uthayashanker R

    2016-01-01

    We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer. PMID:27390600

  7. Unraveling Curcumin Degradation

    PubMed Central

    Gordon, Odaine N.; Luis, Paula B.; Sintim, Herman O.; Schneider, Claus

    2015-01-01

    Curcumin is a dietary anti-inflammatory and chemopreventive agent consisting of two methoxyphenol rings connected by a conjugated heptadienedione chain. Curcumin is unstable at physiological pH and rapidly degrades in an autoxidation reaction to a major bicyclopentadione product in which the 7-carbon chain has undergone oxygenation and double cyclization. Early degradation products (but not the final bicyclopentadione) mediate topoisomerase poisoning and possibly many other activities of curcumin, but it is not known how many and what autoxidation products are formed, nor their mechanism of formation. Here, using [14C2]curcumin as a tracer, seven novel autoxidation products, including two reaction intermediates, were isolated and identified using one- and two-dimensional NMR and mass spectrometry. The unusual spiroepoxide and vinylether reaction intermediates are precursors to the final bicyclopentadione product. A mechanism for the autoxidation of curcumin is proposed that accounts for the addition and exchange of oxygen that have been determined using 18O2 and H218O. Several of the by-products are formed from an endoperoxide intermediate via reactions that are well precedented in lipid peroxidation. The electrophilic spiroepoxide intermediate formed a stable adduct with N-acetylcysteine, suggesting that oxidative transformation is required for biological effects mediated by covalent adduction to protein thiols. The spontaneous autoxidation distinguishes curcumin among natural polyphenolic compounds of therapeutic interest; the formation of chemically diverse reactive and electrophilic products provides a novel paradigm for understanding the polypharmacological effects of curcumin. PMID:25564617

  8. Curcumin treatment provides protection against Trypanosoma cruzi infection

    PubMed Central

    Zhao, Dazhi; Weiss, Louis M.; Tanowitz, Herbert B.

    2013-01-01

    Trypanosoma cruzi, the etiologic agent of Chagas disease, causes an acute myocarditis and chronic cardiomyopathy. The current therapeutic agents for this disease are not always effective and often have severe side effects. Curcumin, a plant polyphenol, has demonstrated a wide range of potential therapeutic effects. In this study, we examined the effect of curcumin on T. cruzi infection in vitro and in vivo. Curcumin pretreatment of fibroblasts inhibited parasite invasion. Treatment reduced the expression of the low density lipoprotein receptor, which is involved in T. cruzi host cell invasion. Curcumin treatment of T. cruzi-infected CD1 mice reduced parasitemia and decreased the parasitism of infected heart tissue. This was associated with a significant reduction in macrophage infiltration and inflammation in both the heart and liver; moreover, curcumin-treated infected mice displayed a 100% survival rate in contrast to the 60% survival rate commonly observed in untreated infected mice. These data are consistent with curcumin modulating infection-induced changes in signaling pathways involved in inflammation, oxidative stress, and apoptosis. These data suggest that curcumin and its derivatives could be a suitable drug for the amelioration of chagasic heart disease. PMID:22215192

  9. Overdose Intake of Curcumin Initiates the Unbalanced State of Bodies.

    PubMed

    Qiu, Peiyu; Man, Shuli; Li, Jing; Liu, Jing; Zhang, Liming; Yu, Peng; Gao, Wenyuan

    2016-04-01

    Curcumin is the major active component of turmeric and widely used as a spice and coloring agent in food. However, its safety evaluation has been little investigated. To evaluate the 90-day subchronic toxicity of curcumin in rats, its general observation, clinical biochemistry, pathology, and metabolomics were evaluated. The results showed that curcumin induced liver injury through the generation of the overexpression of reactive oxygen species (ROS) and pro-inflammatory cytokines IL-6 and the decreases of the levels of antioxidant enzyme SOD and detoxified enzyme GST. Meanwhile, for the self-protection of rats, curcumin treatment activated the transcription of Nrf-2 and elevated the expression of HO-1 to reduce tissue damage. Furthermore, curcumin significantly increased key mRNA levels of HK2, PKM2, LDHA, CES, Cpt1, Cpt2, FASN, and ATP5b and decreased levels of GLUT2 and ACC1 to enhance glycolysis and inhibit lipid metabolism and TCA cycle. Therefore, overdose or long-term intake of curcumin could initiate the unbalanced state of bodies through oxidative stress, inflammation, and metabolic disorders, which induces liver injury. Intermittent administration of curcumin is necessary in our daily lives. PMID:26978516

  10. Enhanced dispersibility and bioactivity of curcumin by encapsulation in casein nanocapsules.

    PubMed

    Pan, Kang; Zhong, Qixin; Baek, Seung Joon

    2013-06-26

    In this work, a novel encapsulation method was studied by spray-drying a warm aqueous ethanol solution with codissolved sodium caseinate (NaCas) and lipophilic food components, using curcumin as a model compound. The encapsulation caused the loss of crystallinity of curcumin. After hydration of spray-dried powder and centrifugation, 137 μg/mL curcumin was dispersed in the transparent dispersion, which was 4 decades higher than its water solubility. Dynamic light scattering and atomic force microscopy results showed that curcumin-loaded casein nanoparticles were bigger than those of NaCas processed at encapsulation conditions but were smaller than those of the native NaCas. The increased nanoparticle dimension, together with fluorescence and FTIR spectroscopy results, suggested that curcumin was entrapped in the nanoparticle core through hydrophobic interactions. The curcumin encapsulated in casein nanoparticles had higher biological activity, as assessed by antioxidant and cell proliferation assays, than pristine curcumin, likely due to the improved dispersibility. This simple approach may be applied to encapsulate various lipophilic bioactive compounds. PMID:23734864

  11. Importance of the Direct Contact of Amorphous Solid Particles with the Surface of Monolayers for the Transepithelial Permeation of Curcumin.

    PubMed

    Kimura, Shunsuke; Kasatani, Sachiha; Tanaka, Megumi; Araki, Kaeko; Enomura, Masakazu; Moriyama, Kei; Inoue, Daisuke; Furubayashi, Tomoyuki; Tanaka, Akiko; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-02-01

    The amorphization has been generally known to improve the absorption and permeation of poorly water-soluble drugs through the enhancement of the solubility. The present study focused on the direct contact of amorphous solid particles with the surface of the membrane using curcumin as a model for water-insoluble drugs. Amorphous nanoparticles of curcumin (ANC) were prepared with antisolvent crystallization method using a microreactor. The solubility of curcumin from ANC was two orders of magnitude higher than that of crystalline curcumin (CC). However, the permeation of curcumin from the saturated solution of ANC was negligible. The transepithelial permeation of curcumin from ANC suspension was significantly increased as compared to CC suspension, while the permeation was unlikely correlated with the solubility, and the increase in the permeation was dependent on the total concentration of curcumin in ANC suspension. The absorptive transport of curcumin (from apical to basal, A to B) from ANC suspension was much higher than the secretory transport (from basal to apical, B to A). In vitro transport of curcumin through air-interface monolayers is large from ANC but negligible from CC particles. These findings suggest that the direct contact of ANC with the absorptive membrane can play an important role in the transport of curcumin from ANC suspension. The results of the study suggest that amorphous particles may be directly involved in the transepithlial permeation of curcumin. PMID:26656401

  12. Superoxide anion and proteasomal dysfunction contribute to curcumin-induced paraptosis of malignant breast cancer cells.

    PubMed

    Yoon, Mi Jin; Kim, Eun Hee; Lim, Jun Hee; Kwon, Taeg Kyu; Choi, Kyeong Sook

    2010-03-01

    Curcumin is considered a pharmacologically safe agent that may be useful in cancer chemoprevention and therapy. Here, we show for the first time that curcumin effectively induces paraptosis in malignant breast cancer cell lines, including MDA-MB-435S, MDA-MB-231, and Hs578T cells, by promoting vacuolation that results from swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). Inhibition of protein synthesis by cycloheximide blocked curcumin-induced vacuolation and subsequent cell death, indicating that protein synthesis is required for this process. The levels of AIP-1/Alix protein, a known inhibitor protein of paraptosis, were progressively downregulated in curcumin-treated malignant breast cancer cells, and AIP-1/Alix overexpression attenuated curcumin-induced death in these cells. ERK2 and JNK activation were positively associated with curcumin-induced cell death. Mitochondrial superoxide was shown to act as a critical early signal in curcumin-induced paraptosis, whereas proteasomal dysfunction was mainly responsible for the paraptotic changes associated with ER dilation. Notably, curcumin-induced paraptotic events were not observed in normal breast cells, including mammary epithelial cells and MCF-10A cells. Taken together, our findings on curcumin-induced paraptosis may provide novel insights into the mechanisms underlying the selective anti-cancer effects of curcumin against malignant cancer cells. PMID:20036734

  13. Structure activity relationship study of curcumin analogues toward the amyloid-beta aggregation inhibitor.

    PubMed

    Endo, Hitoshi; Nikaido, Yuri; Nakadate, Mamiko; Ise, Satomi; Konno, Hiroyuki

    2014-12-15

    Inhibition of the amyloid β aggregation process could possibly prevent the onset of Alzheimer's disease. In this article, we report a structure-activity relationship study of curcumin analogues for anti amyloid β aggregation activity. Compound 7, the ideal amyloid β aggregation inhibitor in vitro among synthesized curcumin analogues, has not only potent anti amyloid β aggregation effects, but also water solubility more than 160 times that of curcumin. In addition, new approaches to improve water solubility of curcumin-type compounds are proposed. PMID:25467149

  14. Interference with Akt signaling pathway contributes curcumin-induced adipocyte insulin resistance.

    PubMed

    Zhang, Deling; Zhang, Yemin; Ye, Mao; Ding, Youming; Tang, Zhao; Li, Mingxin; Zhou, Yu; Wang, Changhua

    2016-07-01

    Previous study has shown that curcumin directly or indirectly suppresses insulin signaling in 3T3-L1 adipocytes. However, the underlying mechanism remains unclear. Here we experimentally demonstrate that curcumin inhibited the ubiquitin-proteasome system (UPS) function, activated autophagy, and reduced protein levels of protein kinase B (Akt) in a dose- and time-dependent manner in 3T3-L1 adipocytes, accompanied with attenuation of insulin-stimulated Akt phosphorylation, plasma membrane translocation of glucose transporter type 4 (GLUT4), and glucose uptake. These in vitro inhibitory effects of curcumin on Akt protein expression and insulin action were reversed by pharmacological and genetic inhibition of autophagy but not by inhibition of the UPS and caspases. In addition, Akt reduction in adipose tissues of mice treated with curcumin could be recovered by administration of autophagy inhibitor bafilomycin A1 (BFA). This new finding provides a novel mechanism by which curcumin induces insulin resistance in adipocytes. PMID:27113027

  15. Renoprotective effect of the antioxidant curcumin: Recent findings☆

    PubMed Central

    Trujillo, Joyce; Chirino, Yolanda Irasema; Molina-Jijón, Eduardo; Andérica-Romero, Ana Cristina; Tapia, Edilia; Pedraza-Chaverrí, José

    2013-01-01

    For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury. PMID:24191240

  16. Synergistic radical scavenging potency of curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes.

    PubMed

    Aadinath, W; Bhushani, Anu; Anandharamakrishnan, C

    2016-07-01

    Curcumin is a highly potent nutraceutical associated with various health benefits. However, its hydrophobic nature affects its bioavailability and bioactivity, and limits nutraceutical applications. Drug-in-cyclodextrin-in-liposome has the ability to mask the hydrophobic nature of drug and achieve better encapsulation. Also, encapsulating iron oxide nanoparticles (IONPs) within liposomes endow additional beneficial functionalities of IONPs. In the present study, curcumin-β-cyclodextrin inclusion complex (IC) and IONPs were co-encapsulated within liposomes (curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes) to achieve the synergistic antioxidant potential of curcumin and IONPs. IC of curcumin-β-cyclodextrin was prepared by a simple rapid method and successful inclusion was confirmed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). Mean diameter of IONPs was found to be 180nm and X-ray diffraction pattern confirmed the formation of hematite nanoparticles. Band gap energy calculated using absorption spectra was 2.25eV, which falls in close proximity with the theoretically calculated values of hematite. Mean diameter of curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes was 67nm and encapsulation efficiency of curcumin was found to be 71%. Further, the co-encapsulated particles possessed significantly low IC50 value (64.7791μg/ml, p<0.01) compared to conventional curcumin liposome and IONPs, indicating its synergistically enhanced radical scavenging property. PMID:27127056

  17. Antioxidant and radical scavenging properties of curcumin.

    PubMed

    Ak, Tuba; Gülçin, Ilhami

    2008-07-10

    Curcumin (diferuoyl methane) is a phenolic compound and a major component of Curcuma longa L. In the present paper, we determined the antioxidant activity of curcumin by employing various in vitro antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH*) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD) radical scavenging activity, total antioxidant activity determination by ferric thiocyanate, total reducing ability determination by the Fe(3+)-Fe(2+) transformation method, superoxide anion radical scavenging by the riboflavin/methionine/illuminate system, hydrogen peroxide scavenging and ferrous ions (Fe(2+)) chelating activities. Curcumin inhibited 97.3% lipid peroxidation of linoleic acid emulsion at 15 microg/mL concentration (20 mM). On the other hand, butylated hydroxyanisole (BHA, 123 mM), butylated hydroxytoluene (BHT, 102 mM), alpha-tocopherol (51 mM) and trolox (90 mM) as standard antioxidants indicated inhibition of 95.4, 99.7, 84.6 and 95.6% on peroxidation of linoleic acid emulsion at 45 microg/mL concentration, respectively. In addition, curcumin had an effective DPPH* scavenging, ABTS*(+) scavenging, DMPD*(+) scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe(3+)) reducing power and ferrous ions (Fe(2+)) chelating activities. Also, BHA, BHT, alpha-tocopherol and trolox, were used as the reference antioxidant and radical scavenger compounds. According to the present study, curcumin can be used in the pharmacological and food industry because of these properties. PMID:18547552

  18. The targets of curcumin.

    PubMed

    Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

    2011-03-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

  19. Targets of curcumin

    PubMed Central

    Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

    2010-01-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

  20. Synthesis and Evaluation of the Anti-Oxidant Capacity of Curcumin Glucuronides, the Major Curcumin Metabolites

    PubMed Central

    Choudhury, Ambar K.; Raja, Suganya; Mahapatra, Sanjata; Nagabhushanam, Kalyanam; Majeed, Muhammed

    2015-01-01

    Curcumin metabolites namely curcumin monoglucuronide and curcumin diglucuronide were synthesized using an alternative synthetic approach. The anti-oxidant potential of these curcumin glucuronides was compared with that of curcumin using DPPH scavenging method and Oxygen Radical Absorbance Capacity (ORAC) assay. The results show that curcumin monoglucuronide exhibits 10 fold less anti-oxidant activity (DPPH method) and the anti-oxidant capacity of curcumin diglucuronide is highly attenuated compared to the anti-oxidant activity of curcumin. PMID:26783957

  1. A novel nanoparticle containing neuritin peptide with grp170 induces a CTL response to inhibit tumor growth.

    PubMed

    Yuan, Bangqing; Shen, Hanchao; Su, Tonggang; Lin, Li; Chen, Ting; Yang, Zhao

    2015-10-01

    Malignant glioma is among the most challenging of all cancers to treat successfully. Despite recent advances in surgery, radiotherapy and chemotherapy, current treatment regimens have only a marginal impact on patient survival. In this study, we constructed a novel nanoparticle containing neuritin peptide with grp170. The nanoparticle could elicit a neuritin-specific cytotoxic T lymphocyte response to lyse glioma cells in vitro. In addition, the nanoparticle could inhibit tumor growth and improve the lifespan of tumor-bearing mice in vivo. Taken together, the results demonstrated that the nanoparticle can inhibit tumor growth and represents a promising therapy for glioma. PMID:26290143

  2. Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes.

    PubMed

    Daverey, Amita; Agrawal, Sandeep K

    2016-10-01

    Oxidative stress plays a critical role in various neurodegenerative diseases, thus alleviating oxidative stress is a potential strategy for therapeutic intervention and/or prevention of neurodegenerative diseases. In the present study, alleviation of oxidative stress through curcumin is investigated in A172 (human glioblastoma cell line) and HA-sp (human astrocytes cell line derived from the spinal cord) astrocytes. H2O2 was used to induce oxidative stress in astrocytes (A172 and HA-sp). Data show that H2O2 induces activation of astrocytes in dose- and time-dependent manner as evident by increased expression of GFAP in A172 and HA-sp cells after 24 and 12h respectively. An upregulation of Prdx6 was also observed in A172 and HA-sp cells after 24h of H2O2 treatment as compared to untreated control. Our data also showed that curcumin inhibits oxidative stress-induced cytoskeleton disarrangement, and impedes the activation of astrocytes by inhibiting upregulation of GFAP, vimentin and Prdx6. In addition, we observed an inhibition of oxidative stress-induced inflammation, apoptosis and mitochondria fragmentation after curcumin treatment. Therefore, our results suggest that curcumin not only protects astrocytes from H2O2-induced oxidative stress but also reverses the mitochondrial damage and dysfunction induced by oxidative stress. This study also provides evidence for protective role of curcumin on astrocytes by showing its effects on attenuating reactive astrogliosis and inhibiting apoptosis. PMID:27423629

  3. Bismuth oxide aqueous colloidal nanoparticles inhibit Candida albicans growth and biofilm formation

    PubMed Central

    Hernandez-Delgadillo, Rene; Velasco-Arias, Donaji; Martinez-Sanmiguel, Juan Jose; Diaz, David; Zumeta-Dube, Inti; Arevalo-Niño, Katiushka; Cabral-Romero, Claudio

    2013-01-01

    Multiresistance among microorganisms to common antimicrobials has become one of the most significant concerns in modern medicine. Nanomaterials are a new alternative to successfully treat the multiresistant microorganisms. Nanostructured materials are used in many fields, including biological sciences and medicine. Recently, it was demonstrated that the bactericidal activity of zero-valent bismuth colloidal nanoparticles inhibited the growth of Streptococcus mutans; however the antimycotic potential of bismuth nanostructured derivatives has not yet been studied. The main objective of this investigation was to analyze the fungicidal activity of bismuth oxide nanoparticles against Candida albicans, and their antibiofilm capabilities. Our results showed that aqueous colloidal bismuth oxide nanoparticles displayed antimicrobial activity against C. albicans growth (reducing colony size by 85%) and a complete inhibition of biofilm formation. These results are better than those obtained with chlorhexidine, nystatin, and terbinafine, the most effective oral antiseptic and commercial antifungal agents. In this work, we also compared the antimycotic activities of bulk bismuth oxide and bismuth nitrate, the precursor metallic salt. These results suggest that bismuth oxide colloidal nanoparticles could be a very interesting candidate as a fungicidal agent to be incorporated into an oral antiseptic. Additionally, we determined the minimum inhibitory concentration for the synthesized aqueous colloidal Bi2O3 nanoparticles. PMID:23637533

  4. Short communication: inhibiting biofilm formation on paper towels through the use of selenium nanoparticles coatings.

    PubMed

    Wang, Qi; Webster, Thomas J

    2013-01-01

    Bacterial infections are commonly found on paper towels and other paper products, leading to the potential spread of bacteria and consequent health concerns. The objective of this in vitro study was to introduce antibacterial properties to standard paper towel surfaces by coating them with selenium nanoparticles. Scanning electron microscopy was used to measure the size and distribution of the selenium coatings on the paper towels. Atomic force microscopy was used to measure the surface roughness of paper towels before and after they were coated with selenium nanoparticles. The amount of selenium precipitated on the paper towels was measured by atomic absorption spectroscopy. In vitro bacterial studies with Staphylococcus aureus were conducted to assess the effectiveness of the selenium coating at inhibiting bacterial growth. Results showed that the selenium nanoparticles coated on the paper towel surface were well distributed with semispherical geometries about 50 nm in diameter. Most importantly, the selenium nanoparticle-coated paper towels inhibited S. aureus growth by 90% after 24 and 72 hours compared with the uncoated paper towels. Thus, the study showed that nanoparticle selenium-coated paper towels may lead to an increased eradication of bacteria in a wider range of clinical environments and in the food industry, thus improving human health. PMID:23378762

  5. Short communication: inhibiting biofilm formation on paper towels through the use of selenium nanoparticles coatings

    PubMed Central

    Wang, Qi; Webster, Thomas J

    2013-01-01

    Bacterial infections are commonly found on paper towels and other paper products, leading to the potential spread of bacteria and consequent health concerns. The objective of this in vitro study was to introduce antibacterial properties to standard paper towel surfaces by coating them with selenium nanoparticles. Scanning electron microscopy was used to measure the size and distribution of the selenium coatings on the paper towels. Atomic force microscopy was used to measure the surface roughness of paper towels before and after they were coated with selenium nanoparticles. The amount of selenium precipitated on the paper towels was measured by atomic absorption spectroscopy. In vitro bacterial studies with Staphylococcus aureus were conducted to assess the effectiveness of the selenium coating at inhibiting bacterial growth. Results showed that the selenium nanoparticles coated on the paper towel surface were well distributed with semispherical geometries about 50 nm in diameter. Most importantly, the selenium nanoparticle-coated paper towels inhibited S. aureus growth by 90% after 24 and 72 hours compared with the uncoated paper towels. Thus, the study showed that nanoparticle selenium-coated paper towels may lead to an increased eradication of bacteria in a wider range of clinical environments and in the food industry, thus improving human health. PMID:23378762

  6. "Clicked" sugar-curcumin conjugate: modulator of amyloid-β and tau peptide aggregation at ultralow concentrations.

    PubMed

    Dolai, Sukanta; Shi, Wei; Corbo, Christopher; Sun, Chong; Averick, Saadyah; Obeysekera, Dinali; Farid, Mina; Alonso, Alejandra; Banerjee, Probal; Raja, Krishnaswami

    2011-12-21

    The synthesis of a water/plasma soluble, noncytotoxic, "clicked" sugar-derivative of curcumin with amplified bioefficacy in modulating amyloid-β and tau peptide aggregation is presented. Curcumin inhibits amyloid-β and tau peptide aggregation at micromolar concentrations; the sugar-curcumin conjugate inhibits Aβ and tau peptide aggregation at concentrations as low as 8 nM and 0.1 nM, respectively. In comparison to curcumin, this conveniently synthesized Alzheimer's drug candidate is a more powerful antioxidant. PMID:22860163

  7. Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles.

    PubMed

    Bimbo, Luis M; Denisova, Oxana V; Mäkilä, Ermei; Kaasalainen, Martti; De Brabander, Jef K; Hirvonen, Jouni; Salonen, Jarno; Kakkola, Laura; Kainov, Denis; Santos, Hélder A

    2013-08-27

    Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi, SaliPhe inhibited IAV infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells. PMID:23889734

  8. Green synthesis of curcumin conjugated nanosilver for the applications in nucleic acid sensing and anti-bacterial activity.

    PubMed

    El Khoury, Elsy; Abiad, Mohamad; Kassaify, Zeina G; Patra, Digambara

    2015-03-01

    Silver nanoparticles (Ag NPs) are often synthesized by chemical and physical methods. Natural and non-toxic molecules are recently being replaced for nanoparticles preparation. In this paper we have used curcumin, which interacts with Ag+ and subsequently synthesizes silver nanoparticles. Further continuation of the reaction often makes aggregation and forms dark brown/black silver oxide. Presence of glycerol in the reaction mixture gives mono-disperse curcumin conjugated Ag NPs, which can be made stable by capping with polyvinylpyrolidone (PVP). XRD data confirm that curcumin conjugated Ag NPs are crystalline in nature with a mean crystalline size of 13.27 nm. The Ag NPs are spherical and in the range of 10-50 nm though their hydrodynamic radius is found to be higher, ∼294 nm, due to polyvinylpyrolidone capping and aggregation of nanoparticles in solution. The production of curcumin conjugated Ag NPs follows first order kinetics and the effect of curcumin concentration during formation of Ag NPs indicates a linear enhancement in the production of Ag NPs with an increase in concentration of curcumin. These curcumin conjugated silver nanoparticles show anti-bacterial activity and can successfully determine nucleic acid (DNA and RNA) in the concentration range 100-1000 ng/mL with a linear regression coefficient >0.997 using Resonance Rayleigh Scattering spectra. PMID:25687098

  9. Zn(II)-curcumin protects against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism.

    PubMed

    Yu, Chuan; Mei, Xue-Ting; Zheng, Yan-Ping; Xu, Dong-Hui

    2014-03-01

    Curcumin can chelate metal ions, forming metallocomplexes. We compared the effects of Zn(II)-curcumin with curcumin against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. Oral administration of Zn(II)-curcumin dose-dependently prevented the ethanol-induced elevation of serum malondialdehyde (MDA) content and reductions in glutathione level and superoxide dismutase (SOD) activity. Zn(II)-curcumin also inhibited ethanol-induced liver injury. Additionally, Zn(II)-curcumin dose-dependently inhibited hemorheological abnormalities, including the ethanol-induced elevation of whole blood viscosity, plasma viscosity, blood viscosity at corrected hematocrit (45%), erythrocyte aggregation index, erythrocyte rigidity index and hematocrit. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively elevated SOD activity, ameliorated liver injury and improved hemorheological variables. These results suggest that Zn(II)-curcumin protected the rats from ethanol-induced liver injury and hemorheological abnormalities via the synergistic effect of curcumin and zinc. PMID:24607687

  10. In Vitro Study on Antihypertensive and Antihypercholesterolemic Effects of a Curcumin Nanoemulsion

    PubMed Central

    Rachmawati, Heni; Soraya, Irene Surya; Kurniati, Neng Fisheri; Rahma, Annisa

    2016-01-01

    Atherosclerosis and hypertension can potentially progess into dangerous cardiovascular diseases such as myocardial infarction and stroke. Statins are widely used to lower cholesterol levels while antihypertensive agents such as captopril are widely prescribed to treat high blood pressure. Curcumin, a phenolic compound isolated from Curcuma domestica, has been proven effective for a broad spectrum of diseases, including hypertension and hypercholesterolemia. Therefore, curcumin is quite promising as an alternative therapeutic compound. Our previous studies have proven a significant increase in physical properties, bioavailability, and stability of curcumin when encapsulated in a nanoemulsion. The purpose of this study was to assess the ability of the nanoemulsion in enhancing curcumin activity as a antihypertensive and antihypercholesterolemic agent. The formulation and preparation method of the curcumin nanoemulsion have been developed in our previous study. Physical characterization was performed, including measurement of droplet size, polidispersity index, zeta potential, entrapment efficiency, and loading capacity. Antihypertensive activity of curcumin was evaluated by determining Angiotensin Converting Enzyme (ACE) inhibition in vitro. A substrate for ACE, hippuryl-L-histidyl-L-leucine was allowed to react with ACE, resulting in hippuric acid formation as the product. The degree of ACE inhibition by curcumin was represented by the amount of hippuric acid formed. Antihypercholesterolemic activity of curcumin was studied using the HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance which represents the oxidation of NADPH by the catalytic subunit of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in the presence of the substrate HMG-CoA. Curcumin is known to have no significant difference in inhibiting ACE compared to Captopril, but when it was incorporated in the self

  11. In Vitro Study on Antihypertensive and Antihypercholesterolemic Effects of a Curcumin Nanoemulsion.

    PubMed

    Rachmawati, Heni; Soraya, Irene Surya; Kurniati, Neng Fisheri; Rahma, Annisa

    2016-01-01

    Atherosclerosis and hypertension can potentially progess into dangerous cardiovascular diseases such as myocardial infarction and stroke. Statins are widely used to lower cholesterol levels while antihypertensive agents such as captopril are widely prescribed to treat high blood pressure. Curcumin, a phenolic compound isolated from Curcuma domestica, has been proven effective for a broad spectrum of diseases, including hypertension and hypercholesterolemia. Therefore, curcumin is quite promising as an alternative therapeutic compound. Our previous studies have proven a significant increase in physical properties, bioavailability, and stability of curcumin when encapsulated in a nanoemulsion. The purpose of this study was to assess the ability of the nanoemulsion in enhancing curcumin activity as a antihypertensive and antihypercholesterolemic agent. The formulation and preparation method of the curcumin nanoemulsion have been developed in our previous study. Physical characterization was performed, including measurement of droplet size, polidispersity index, zeta potential, entrapment efficiency, and loading capacity. Antihypertensive activity of curcumin was evaluated by determining Angiotensin Converting Enzyme (ACE) inhibition in vitro. A substrate for ACE, hippuryl-L-histidyl-L-leucine was allowed to react with ACE, resulting in hippuric acid formation as the product. The degree of ACE inhibition by curcumin was represented by the amount of hippuric acid formed. Antihypercholesterolemic activity of curcumin was studied using the HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance which represents the oxidation of NADPH by the catalytic subunit of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in the presence of the substrate HMG-CoA. Curcumin is known to have no significant difference in inhibiting ACE compared to Captopril, but when it was incorporated in the self

  12. Curcumin exerts antitumor effects in retinoblastoma cells by regulating the JNK and p38 MAPK pathways.

    PubMed

    Yu, Xiaoming; Zhong, Jingtao; Yan, Li; Li, Jie; Wang, Hui; Wen, Yan; Zhao, Yu

    2016-09-01

    Curcumin, a naturally occurring polyphenolic compound present in turmeric (Curcuma longa), exerts antitumor effects in various types of malignancy. However, the precise mechanisms responsible for the effects of curcumin on retinoblastoma (RB) cells have not been fully explored. In the present study, the molecular mechanisms by which curcumin exerts its anticancer effects in RB Y79 cells were investigated. The results showed that curcumin reduced cell viability in Y79 cells. Curcumin induced G1 phase arrest through downregulating the expression of cyclin D3 and cyclin-dependent kinase (CDK)2/6 and upregulating the expression of CDK inhibitor proteins p21 and p27. Curcumin-induced apoptosis of Y79 cells occurred through the activation of caspases-9/-3. Moreover, flow cytometric analysis showed that curcumin induced mitochondrial membrane potential (∆Ψm) collapse in Y79 cells. We also found that curcumin induced the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). JNK and p38 MAPK inhibitors significantly suppressed curcumin‑induced activation of caspases-9/-3 and inhibited the apoptosis of Y79 cells. Taken together, our results suggest that curcumin induced the apoptosis of Y79 cells through the activation of JNK and p38 MAPK pathways. These findings provide a novel treatment strategy for human RB. PMID:27432244

  13. Quantum Chemical and Docking Insights into Bioavailability Enhancement of Curcumin by Piperine in Pepper.

    PubMed

    Patil, Vaishali M; Das, Sukanya; Balasubramanian, Krishnan

    2016-05-26

    We combine quantum chemical and molecular docking techniques to provide new insights into how piperine molecule in various forms of pepper enhances bioavailability of a number of drugs including curcumin in turmeric for which it increases its bioavailability by a 20-fold. We have carried out docking studies of quantum chemically optimized piperine structure binding to curcumin, CYP3A4 in cytochrome P450, p-Glycoprotein and UDP-glucuronosyltransferase (UGT), the enzyme responsible for glucuronosylation, which increases the solubility of curcumin. All of these studies establish that piperine binds to multiple sites on the enzymes and also intercalates with curcumin forming a hydrogen bonded complex with curcumin. The conjugated network of double bonds and the presence of multiple charge centers of piperine offer optimal binding sites for piperine to bind to enzymes such as UDP-GDH, UGT, and CYP3A4. Piperine competes for curcumin's intermolecular hydrogen bonding and its stacking propensity by hydrogen bonding with enolic proton of curcumin. This facilitates its metabolic transport, thereby increasing its bioavailability both through intercalation into curcumin layers through intermolecular hydrogen bonding, and by inhibiting enzymes that cause glucuronosylation of curcumin. PMID:27111639

  14. Curcumin loaded mesoporous silica: an effective drug delivery system for cancer treatment.

    PubMed

    Kotcherlakota, Rajesh; Barui, Ayan Kumar; Prashar, Sanjiv; Fajardo, Mariano; Briones, David; Rodríguez-Diéguez, Antonio; Patra, Chitta Ranjan; Gómez-Ruiz, Santiago

    2016-03-01

    In the present study, we report the delivery of anti-cancer drug curcumin to cancer cells using mesoporous silica materials. A series of mesoporous silica material based drug delivery systems (S2, S4 and S6) were first designed and developed through the amine functionalization of KIT-6, MSU-2 and MCM-41 followed by the loading of curcumin. The curcumin loaded materials were characterized with several physico-chemical techniques and thoroughly screened on cancer cells to evaluate their in vitro drug delivery efficacy. All the curcumin loaded silica materials exhibited higher cellular uptake and inhibition of cancer cell viability compared to pristine curcumin. The effective internalization of curcumin in cancer cells through the mesoporous silica materials initiated the generation of intracellular reactive oxygen species and the down regulation of poly ADP ribose polymerase (PARP) enzyme levels compared to free curcumin leading to the activation of apoptosis. This study shows that the anti-cancer activity of curcumin can be potentiated by loading onto mesoporous silica materials. Therefore, we strongly believe that mesoporous silica based curcumin loaded drug delivery systems may have future potential applications for the treatment of cancers. PMID:26674254

  15. Capsaicin-Coated Silver Nanoparticles Inhibit Amyloid Fibril Formation of Serum Albumin.

    PubMed

    Anand, Bibin G; Dubey, Kriti; Shekhawat, Dolat Singh; Kar, Karunakar

    2016-06-21

    We have synthesized capsaicin-coated silver nanoparticles (AgNPs(Cap)) and have tested their anti-amyloid activity, considering serum albumin (BSA) as a model protein. We found that amyloid formation of BSA was strongly suppressed in the presence of AgNPs(Cap). However, isolated capsaicin and uncapped control nanoparticles did not show such an inhibition effect. Bioinformatics analysis reveals CH-π and H-bonding interactions between capsaicin and BSA in the formation of the protein-ligand complex. These results suggest the significance of surface functionalization of nanoparticles with capsaicin, which probably allows capsaicin to effectively interact with the key residues of the amyloidogenic core of BSA. PMID:27243335

  16. Curcumin AntiCancer Studies in Pancreatic Cancer.

    PubMed

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

    2016-01-01

    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

  17. Curcumin AntiCancer Studies in Pancreatic Cancer

    PubMed Central

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

    2016-01-01

    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

  18. Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

    PubMed Central

    Ghosh, Aparajita; Banerjee, Tanushree; Bhandary, Suman; Surolia, Avadhesha

    2014-01-01

    Aim The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results The nanopreparation was found to be non-toxic and had a particle size distribution of 20–50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration [IC50]: 0.5 μM) was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 μM). Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system. PMID:25484584

  19. Intranasal curcumin and its evaluation in murine model of asthma.

    PubMed

    Subhashini; Chauhan, Preeti S; Kumari, Sharda; Kumar, Jarajana Pradeep; Chawla, Ruchi; Dash, D; Singh, Mandavi; Singh, Rashmi

    2013-11-01

    Curcumin, a phytochemical present in turmeric, rhizome of Curcuma longa, has been shown to have a wide variety of pharmacological activities including anti-inflammatory, anti-allergic and anti-asthmatic properties. Curcumin is known for its low systemic bioavailability and rapid metabolization through oral route and has limited its applications. Over the recent decades, the interest in intranasal delivery as a non-invasive route for drugs has increased as target tissue for drug delivery since nasal mucosa offers numerous benefits. In this study, we evaluated intranasal curcumin following its absorption through nasal mucosa by a sensitive and validated high-performance liquid chromatography (HPLC) method for the determination of intranasal curcumin in mouse blood plasma and lung tissue. Intranasal curcumin has been detected in plasma after 15 min to 3 h at pharmacological dose (5 mg/kg, i.n.), which has shown anti-asthmatic potential by inhibiting bronchoconstriction and inflammatory cell recruitment to the lungs. At considerably lower doses has proved better than standard drug disodium cromoglycate (DSCG 50 mg/kg, i.p.) by affecting inflammatory cell infiltration and histamine release in mouse model of asthma. HPLC detection revealed that curcumin absorption in lungs has started after 30 min following intranasal administration and retained till 3h then declines. Present investigations suggest that intranasal curcumin (5.0 mg/kg, i.n.) has effectively being absorbed and detected in plasma and lungs both and suppressed airway inflammations at lower doses than the earlier doses used for detection (100-200 mg/kg, i.p.) for pharmacological studies (10-20 mg/kg, i.p.) in mouse model of asthma. Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops to prevent airway inflammations and bronchoconstrictions in asthma without any side effect. PMID:24021755

  20. Titanium oxide nanoparticle instillation induces inflammation and inhibits lung development in mice

    PubMed Central

    Stanishevsky, Andrei; Bulger, Arlene; Halloran, Brian; Steele, Chad; Vohra, Yogesh; Matalon, Sadis

    2013-01-01

    Nanoparticles are used in an increasing number of biomedical, industrial, and food applications, but their safety profiles in developing organisms, including the human fetus and infant, have not been evaluated. Titanium oxide (TiO2) nanoparticles, which are commonly used in cosmetics, sunscreens, paints, and food, have been shown to induce emphysema and lung inflammation in adult mice. We hypothesized that exposure of newborn mice to TiO2 would induce lung inflammation and inhibit lung development. C57BL/6 mice were exposed to TiO2 (anatase; 8–10 nm) nanoparticles by intranasal instillation as a single dose on postnatal day 4 (P4) or as three doses on postnatal days 4, 7, and 10 (each dose = 1 μg/g body wt). Measurements of lung function (compliance and resistance), development (morphometry), inflammation (histology; multiplex analysis of bronchoalveolar lavage fluid for cytokines; PCR array and multiplex analysis of lung homogenates for cytokines) was performed on postnatal day 14. It was observed that a single dose of TiO2 nanoparticles led to inflammatory cell influx, and multiple doses led to increased inflammation and inhibition of lung development without significant effects on lung function. Macrophages were noted to take up the TiO2 nanoparticles, followed by polymorphonuclear infiltrate. Multiple cytokines and matrix metalloproteinase-9 were increased in lung homogenates, and VEGF was reduced. These results suggest that exposure of the developing lung to nanoparticles may lead to ineffective clearance by macrophages and persistent inflammation with resulting effects on lung development and may possibly impact the risk of respiratory disorders in later life. PMID:23220372

  1. Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular responses.

    PubMed

    Aggarwal, Bharat B; Deb, Lokesh; Prasad, Sahdeo

    2015-01-01

    Curcumin (diferuloylmethane), a golden pigment from turmeric, has been linked with antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antidiabetic properties. Most of the these activities have been assigned to methoxy, hydroxyl, α,β-unsaturated carbonyl moiety or to diketone groups present in curcumin. One of the major metabolites of curcumin is tetrahydrocurcumin (THC), which lacks α,β-unsaturated carbonyl moiety and is white in color. Whether THC is superior to curcumin on a molecular level is unclear and thus is the focus of this review. Various studies suggest that curcumin is a more potent antioxidant than THC; curcumin (but not THC) can bind and inhibit numerous targets including DNA (cytosine-5)-methyltransferase-1, heme oxygenase-1, Nrf2, β-catenin, cyclooxygenase-2, NF-kappaB, inducible nitric oxide synthase, nitric oxide, amyloid plaques, reactive oxygen species, vascular endothelial growth factor, cyclin D1, glutathione, P300/CBP, 5-lipoxygenase, cytosolic phospholipase A2, prostaglandin E2, inhibitor of NF-kappaB kinase-1, -2, P38MAPK, p-Tau, tumor necrosis factor-α, forkhead box O3a, CRAC; curcumin can inhibit tumor cell growth and suppress cellular entry of viruses such as influenza A virus and hepatitis C virus much more effectively than THC; curcumin affects membrane mobility; and curcumin is also more effective than THC in suppressing phorbol-ester-induced tumor promotion. Other studies, however, suggest that THC is superior to curcumin for induction of GSH peroxidase, glutathione-S-transferase, NADPH: quinone reductase, and quenching of free radicals. Most studies have indicated that THC exhibits higher antioxidant activity, but curcumin exhibits both pro-oxidant and antioxidant properties. PMID:25547723

  2. Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels.

    PubMed

    Chen, Qijing; Tao, Jie; Hei, Hongya; Li, Fangping; Wang, Yunman; Peng, Wen; Zhang, Xuemei

    2015-01-01

    Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID:26672753

  3. Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels

    PubMed Central

    Hei, Hongya; Li, Fangping; Wang, Yunman; Peng, Wen; Zhang, Xuemei

    2015-01-01

    Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID:26672753

  4. Mo polyoxometalate nanoparticles inhibit tumor growth and vascular endothelial growth factor induced angiogenesis

    NASA Astrophysics Data System (ADS)

    Zheng, Wenjing; Yang, Licong; Liu, Ying; Qin, Xiuying; Zhou, Yanhui; Zhou, Yunshan; Liu, Jie

    2014-06-01

    Tumor growth depends on angiogenesis, which can furnish the oxygen and nutrients that proliferate tumor cells. Thus, blocking angiogenesis can be an effective strategy to inhibit tumor growth. In this work, three typical nanoparticles based on polyoxometalates (POMs) have been prepared; we investigated their capability as antitumor and anti-angiogenesis agents. We found that Mo POM nanoparticles, especially complex 3, inhibited the growth of human hepatocellular liver carcinoma cells (HepG2) through cellular reactive oxygen species levels’ elevation and mitochondrial membrane potential damage. Complex 3 also suppressed the proliferation, migration, and tube formation of endothelial cells in vitro and chicken chorioallantoic membrane development ex vivo. Furthermore, western blot analysis of cell signaling molecules indicated that Mo POMs blocked the vascular endothelial growth factor receptor 2-mediated ERK1/2 and AKT signaling pathways in endothelial cells. Using transmission electron microscopy, we demonstrated their cellular uptake and localization within the cytoplasm of HepG2 cells. These results indicate that, owing to the extraordinary physical and chemical properties, Mo POM nanoparticles can significantly inhibit tumor growth and angiogenesis, which makes them potential drug candidates in anticancer and anti-angiogenesis therapies.

  5. Zerovalent bismuth nanoparticles inhibit Streptococcus mutans growth and formation of biofilm

    PubMed Central

    Hernandez-Delgadillo, Rene; Velasco-Arias, Donaji; Diaz, David; Arevalo-Niño, Katiushka; Garza-Enriquez, Marianela; De la Garza-Ramos, Myriam A; Cabral-Romero, Claudio

    2012-01-01

    Background and methods Despite continuous efforts, the increasing prevalence of resistance among pathogenic bacteria to common antibiotics has become one of the most significant concerns in modern medicine. Nanostructured materials are used in many fields, including biological sciences and medicine. While some bismuth derivatives has been used in medicine to treat vomiting, nausea, diarrhea, and stomach pain, the biocidal activity of zerovalent bismuth nanoparticles has not yet been studied. The objective of this investigation was to analyze the antimicrobial activity of bismuth nanoparticles against oral bacteria and their antibiofilm capabilities. Results Our results showed that stable colloidal bismuth nanoparticles had 69% antimicrobial activity against Streptococcus mutans growth and achieved complete inhibition of biofilm formation. These results are similar to those obtained with chlorhexidine, the most commonly used oral antiseptic agent. The minimal inhibitory concentration of bismuth nanoparticles that interfered with S. mutans growth was 0.5 mM. Conclusion These results suggest that zerovalent bismuth nanoparticles could be an interesting antimicrobial agent to be incorporated into an oral antiseptic preparation. PMID:22619547

  6. ZnO nanoparticles inhibit Pseudomonas aeruginosa biofilm formation and virulence factor production.

    PubMed

    Lee, Jin-Hyung; Kim, Yong-Guy; Cho, Moo Hwan; Lee, Jintae

    2014-12-01

    The opportunistic pathogen Pseudomonas aeruginosa produces a variety of virulence factors, and biofilms of this bacterium are much more resistant to antibiotics than planktonic cells. Thirty-six metal ions have been investigated to identify antivirulence and antibiofilm metal ions. Zinc ions and ZnO nanoparticles were found to markedly inhibit biofilm formation and the production of pyocyanin, Pseudomonas quinolone signal (PQS), pyochelin, and hemolytic activity of P. aeruginosa without affecting the growth of planktonic cells. Transcriptome analyses showed that ZnO nanoparticles induce the zinc cation efflux pump czc operon and several important transcriptional regulators (porin gene opdT and type III repressor ptrA), but repress the pyocyanin-related phz operon, which explains observed phenotypic changes. A mutant study showed that the effects of ZnO nanoparticles on the control of pyocyanin production and biofilm formation require the czc regulator CzcR. In addition, ZnO nanoparticles markedly increased the cellular hydrophilicity of P. aeruginosa cells. Our results support that ZnO nanoparticles are potential antivirulence materials against recalcitrant P. aeruginosa infections and possibly other important pathogens. PMID:24958247

  7. Recent Advances of Curcumin and its Analogues in Breast Cancer Prevention and Treatment

    PubMed Central

    Mock, Charlotta D; Jordan, Brian C; Selvam, Chelliah

    2016-01-01

    More than 230,000 diagnosed cases of invasive breast cancer in women was estimated in 2014 and an expected 40,000 deaths attributed to the aggressive carcinoma. An effective approach to diminish the morbidity and mortality of breast cancer is the development of chemopreventive and chemotherapeutic agents. Nutraceuticals have demonstrated their ability to proficiently halt carcinogenesis. The administration of natural compounds able to effectively serve as chemoprevention and chemotherapeutics without causing harm or adverse effects is imperative. Curcumin derived from the rhizome of Curcuma longa L., is a common spice of India, used for centuries because of its medicinal properties. The main component of curcumin possesses a wide range of biological activities; anti-proliferative, anti-inflammatory, and apoptotic characteristics modulated through the inactivation of pathways such as EGK and Akt/mTOR. In addition, curcumin alters the expression of cytokines, transcription factors, and enzymes involved in cell vitality. The in vivo application of curcumin in breast cancer is hindered by its limited bioavailabiity. The synthesis of curcumin analogues and delivery via nanoparticles has demonstrated enhanced bioavailability of curcumin in the malignancy. This review focuses on recent developments in the use of curcumin, curcumin analogues, and novel delivery systems as a preventive and therapeutic method for breast cancer. PMID:27103993

  8. Curcumin suppresses the dynamic instability of microtubules, activates the mitotic checkpoint and induces apoptosis in MCF-7 cells.

    PubMed

    Banerjee, Mithu; Singh, Parminder; Panda, Dulal

    2010-08-01

    In this study, curcumin, a potential anticancer agent, was found to dampen the dynamic instability of individual microtubules in living MCF-7 cells. It strongly reduced the rate and extent of shortening states, and modestly reduced the rate and extent of growing states. In addition, curcumin decreased the fraction of time microtubules spent in the growing state and strongly increased the time microtubules spent in the pause state. Brief treatment with curcumin depolymerized mitotic microtubules, perturbed microtubule-kinetochore attachment and disturbed the mitotic spindle structure. Curcumin also perturbed the localization of the kinesin protein Eg5 and induced monopolar spindle formation. Further, curcumin increased the accumulation of Mad2 and BubR1 at the kinetochores, indicating that it activated the mitotic checkpoint. In addition, curcumin treatment increased the metaphase/anaphase ratio, indicating that it can delay mitotic progression from the metaphase to anaphase. We provide evidence suggesting that the affected cells underwent apoptosis via the p53-dependent apoptotic pathway. The results support the idea that kinetic stabilization of microtubule dynamics assists in the nuclear translocation of p53. Curcumin exerted additive effects when combined with vinblastine, a microtubule depolymerizing drug, whereas the combination of curcumin with paclitaxel, a microtubule-stabilizing drug, produced an antagonistic effect on the inhibition of MCF-7 cell proliferation. The results together suggested that curcumin inhibited MCF-7 cell proliferation by inhibiting the assembly dynamics of microtubules. PMID:20646066

  9. How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies

    PubMed Central

    Shen, Liang; Liu, Cui-Cui; An, Chun-Yan; Ji, Hong-Fang

    2016-01-01

    Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. However, its poor systemic bioavailability fails to explain the potent pharmacological effects and hinders its clinical application. Using experimental and theoretical approaches, we compared curcumin and its degradation products for its biological activities against Alzheimer’s disease (AD), including the superoxide anion radical (O2.–)-scavenging activity, Aβ fibrils (fAβ) formation-inhibiting activity, and enzymatic inhibition activity. We showed that compared to the parent compound curcumin, the degradation products mixture possessed higher O2.–-scavenging activity and stronger inhibition against fAβ formation. The docking simulations revealed that the bioactive degradation products should make important contribution to the experimentally observed enzymatic inhibition activities of curcumin. Given that curcumin is readily degraded under physiological condition, our findings strongly suggested that the degradation products should make important contribution to the diverse biological activities of curcumin. Our novel findings not only provide novel insights into the complex pharmacology of curcumin due to its poor bioavailability, but also open new avenues for developing therapeutic applications of this natural product. PMID:26887346

  10. Therapeutic roles of curcumin: lessons learned from clinical trials.

    PubMed

    Gupta, Subash C; Patchva, Sridevi; Aggarwal, Bharat B

    2013-01-01

    Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn's disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin's pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the

  11. Thrombin-inhibiting nanoparticles rapidly constitute versatile and detectable anticlotting surfaces

    NASA Astrophysics Data System (ADS)

    Wheatley Myerson, Jacob; He, Li; Allen, John Stacy; Williams, Todd; Lanza, Gregory; Tollefsen, Douglas; Caruthers, Shelton; Wickline, Samuel

    2014-09-01

    Restoring an antithrombotic surface to suppress ongoing thrombosis is an appealing strategy for treatment of acute cardiovascular disorders such as erosion of atherosclerotic plaque. An antithrombotic surface would present an alternative to systemic anticoagulation with attendant risks of bleeding. We have designed thrombin-targeted nanoparticles (NPs) that bind to sites of active clotting to extinguish local thrombin activity and inhibit platelet deposition while exhibiting only transient systemic anticoagulant effects. Perfluorocarbon nanoparticles (PFC NP) were functionalized with thrombin inhibitors (either D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone or bivalirudin) by covalent attachment of more than 15 000 inhibitors to each PFC NP. Fibrinopeptide A (FPA) ELISA demonstrated that thrombin-inhibiting NPs prevented cleavage of fibrinogen by both free and clot-bound thrombin. Magnetic resonance imaging (MRI) confirmed that a layer of thrombin-inhibiting NPs prevented growth of clots in vitro. Thrombin-inhibiting NPs were administered in vivo to C57BL6 mice subjected to laser injury of the carotid artery. NPs significantly delayed thrombotic occlusion of the artery, whereas an equivalent bolus of free inhibitor was ineffective. For thrombin-inhibiting NPs, only a short-lived (˜10 min) systemic effect on bleeding time was observed, despite prolonged clot inhibition. Imaging and quantification of in vivo antithrombotic NP layers was demonstrated by MRI of the PFC NP. 19F MRI confirmed colocalization of particles with arterial thrombi, and quantitative 19F spectroscopy demonstrated specific binding and retention of thrombin-inhibiting NPs in injured arteries. The ability to rapidly form and image a new antithrombotic surface in acute vascular syndromes while minimizing risks of bleeding would permit a safer method of passivating active lesions than current systemic anticoagulant regimes.

  12. CO-DELIVERY OF NATURAL METABOLIC INHIBITORS IN A SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM FOR IMPROVED ORAL BIOAVAILABILITY OF CURCUMIN

    PubMed Central

    Grill, Alex E.; Koniar, Brenda; Panyam, Jayanth

    2014-01-01

    In spite of its well-documented anticancer chemopreventive and therapeutic activity, the clinical development of curcumin has been limited by its poor oral bioavailability. Curcumin has low aqueous solubility and undergoes extensive first pass metabolism following oral dosing. We hypothesized that oral bioavailability of curcumin can be enhanced by increasing its absorption and decreasing its metabolic clearance simultaneously. To test this hypothesis, we formulated curcumin with naturally occurring UGT inhibitors (piperine, quercetin, tangeretin, and silibinin) in a self-microemulsifying drug delivery system (SMEDDS). Mouse liver microsome studies showed that silibinin and quercetin inhibited curcumin glucuronidation effectively. When dosed orally in mice, the SMEDDS containing curcumin alone increased curcumin glucuronide concentrations in plasma without significantly affecting parent drug concentration. Of the four inhibitors examined in vivo, silibinin significantly improved the Cmax (0.15 μM vs. 0.03 μM for curcumin SMEDDS) and the overall bioavailability (3.5-fold vs. curcumin SMEDDS) of curcumin. Previous studies have shown that silibinin has anticancer activity as well. Thus, co-delivery of silibinin with curcumin in SMEDDS represents a novel and promising approach to improve curcumin bioavailability. PMID:25422796

  13. Lipid Based Nanosystems for Curcumin: Past, Present and Future.

    PubMed

    Nayak, Aditya P; Mills, Tom; Norton, Ian

    2016-01-01

    Curcumin is one of the principle bioactive compounds used in the ayurvedic medicine system that has the history of over 5000 years for human use. Curcumin an "Indian Gold" is used to treat simple ailments like the common cold to severe life threatening diseases like cancer, and HIV. Though its contribution is immense for the health protection and disease prevention, its clinical use is limited due to its susceptible nature to alkaline pH, high temperature, presence of oxygen and light. Hence it becomes extremely difficult to maintain its bioactivity during processing, storage and consumption. Recent advancements in the application of nanotechnology to curcumin offer an opportunity to enhance its stability, bioactivity and to overcome its pharmacokinetic mismatch. This in turn helps to bridge the gaps that exist between its bench top research data to its clinical findings. Among the various types of nano/micro delivery systems, lipid based delivery systems are well studied and are the best suited delivery systems to enhance the stability and pharmacokinetic profile of curcumin both for pharma and the food application. In the current review, effort will be made to recapitulate the work done in the past to use lipid based delivery systems (liposomes, solid lipid nanoparticles, and emulsions) to enhance the application of curcumin for health promotion and disease prevention. Further, future prospects for the utilization of these lipid-based delivery systems will be discussed in detail. PMID:27306091

  14. Reactive Oxygen Species Mediated Bacterial Biofilm Inhibition via Zinc Oxide Nanoparticles and Their Statistical Determination

    PubMed Central

    Dwivedi, Sourabh; Wahab, Rizwan; Khan, Farheen; Mishra, Yogendra K.; Musarrat, Javed; Al-Khedhairy, Abdulaziz A.

    2014-01-01

    The formation of bacterial biofilm is a major challenge in clinical applications. The main aim of this study is to describe the synthesis, characterization and biocidal potential of zinc oxide nanoparticles (NPs) against bacterial strain Pseudomonas aeruginosa. These nanoparticles were synthesized via soft chemical solution process in a very short time and their structural properties have been investigated in detail by using X-ray diffraction and transmission electron microscopy measurements. In this work, the potential of synthesized ZnO-NPs (∼10–15 nm) has been assessed in-vitro inhibition of bacteria and the formation of their biofilms was observed using the tissue culture plate assays. The crystal violet staining on biofilm formation and its optical density revealed the effect on biofilm inhibition. The NPs at a concentration of 100 µg/mL significantly inhibited the growth of bacteria and biofilm formation. The biofilm inhibition by ZnO-NPs was also confirmed via bio-transmission electron microscopy (Bio-TEM). The Bio-TEM analysis of ZnO-NPs treated bacteria confirmed the deformation and damage of cells. The bacterial growth in presence of NPs concluded the bactericidal ability of NPs in a concentration dependent manner. It has been speculated that the antibacterial activity of NPs as a surface coating material, could be a feasible approach for controlling the pathogens. Additionally, the obtained bacterial solution data is also in agreement with the results from statistical analytical methods. PMID:25402188

  15. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK

    SciTech Connect

    Li, Ying; Li, Jia; Li, Shanshan; Li, Yi; Wang, Xiangxiang; Liu, Baolin; Fu, Qiang; Ma, Shiping

    2015-07-01

    Curcumin is a natural polyphenolic compound in Curcuma longa with beneficial effects on neuronal protection. This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essential for the suppression of ER stress. As a result, curcumin reduced TXNIP expression and inhibited NLRP3 inflammasome activation by downregulation of NLRP3 and cleaved caspase-1 induction, and thus reduced IL-1β secretion. Specific fluorescent probe and flow cytometry analysis showed that curcumin prevented mitochondrial malfunction and protected cell survival from glutamate neurotoxicity. Moreover, oral administration of curcumin reduced brain infarct volume and attenuated neuronal damage in rats subjected to middle cerebral artery occlusion. Immunohistochemistry showed that curcumin inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region. Together, these results showed that curcumin attenuated glutamate neurotoxicity by inhibiting ER stress-associated TXNIP/NLRP3 inflammasome activation via the regulation of AMPK, and thereby protected the hippocampus from ischemic insult. - Highlights: • Curcumin attenuates glutamate neurotoxicity in the hippocampus. • Curcumin suppresses ER stress in glutamate-induced hippocampus slices. • Curcumin inhibits TXNIP/NLRP3 inflammasome activation. • Regulation of AMPK by curcumin contributes to suppressing ER stress.

  16. Promoting tumor penetration of nanoparticles for cancer stem cell therapy by TGF-β signaling pathway inhibition.

    PubMed

    Zuo, Zu-Qi; Chen, Kai-Ge; Yu, Xiao-Yuan; Zhao, Gui; Shen, Song; Cao, Zhi-Ting; Luo, Ying-Li; Wang, Yu-Cai; Wang, Jun

    2016-03-01

    Cancer stem cells (CSCs), which hold a high capacity for self-renewal, play a central role in the development, metastasis, and recurrence of various malignancies. CSCs must be eradicated to cure instances of cancer; however, because they can reside far from tumor vessels, they are not easily targeted by drug agents carried by nanoparticle-based drug delivery systems. We herein demonstrate that promoting tumor penetration of nanoparticles by transforming growth factor β (TGF-β) signaling pathway inhibition facilitates CSC therapy. In our study, we observed that although nanoparticles carrying siRNA targeting the oncogene polo-like kinase 1 (Plk1) efficiently killed breast CSCs derived from MDA-MB-231 cells in vitro, this intervention enriched CSCs in the residual tumor tissue following systemic treatment. However, inhibition of the TGF-β signaling pathway with LY364947, an inhibitor of TGF-β type I receptor, promoted the penetration of nanoparticles in tumor tissue, significantly ameliorating the intratumoral distribution of nanoparticles in MDA-MB-231 xenografts and further leading to enhanced internalization of nanoparticles by CSCs. As a result, synergistic treatment with a nanoparticle drug delivery system and LY364947 inhibited tumor growth and reduced the proportion of CSCs in vivo. This study suggests that enhanced tumor penetration of drug-carrying nanoparticles can enhance CSCs clearance in vivo and consequently provide superior anti-tumor effects. PMID:26751819

  17. CRM1 is a cellular target of curcumin: new insights for the myriad of biological effects of an ancient spice.

    PubMed

    Niu, Mingshan; Wu, Sijin; Mao, Lei; Yang, Yongliang

    2013-10-01

    Curcumin is the major constituent of turmeric plant, an ancient spice widely used in Indian cuisine and traditional herbal medicine. Recently, the potential medical use of curcumin as anti-cancer and anti-inflammatory agent has set off an upsurge in research into the mechanism for its broad biological effects. We showed that CRM1, an important nuclear exportin, is a cellular target of curcumin by serious experimental and theoretical investigation. Using a nuclear export functional assay, we observed a clear and rapid shift of cargo proteins from a cytoplasmic localization to the nucleus when treated with curcumin or its structural analogue dibenzylideneacetone (DBA). We demonstrated that curcumin could specifically target the conserved Cys(528) of CRM1 through mass spectrometric analysis and in vivo experiments. Furthermore, computational modeling has revealed that curcumin could be correctly docked into the hydrophobic pocket of CRM1 judged from shape complementarity and putative molecular interactions. The Michael acceptor moiety on curcumin is within the appropriate distance to enable Michael reaction with Cys residue of CRM1. More importantly, we showed that nuclear retention of FOXO1 could be observed in the presence of Leptomycin B (LMB) or curcumin whereas in cells expressing the CRM1-Cys(528) mutant, only a cytoplasmic localization was observed. The inhibition of nuclear traffic by curcumin may account for its myriad of biological effects, particularly for its therapeutic properties in cancer and inflammatory diseases. Our findings may have important implications for further clinical investigation of curcumin. PMID:23829533

  18. Influence of cosolvents, ionic strength and the method of sample preparation on the solubilization of curcumin by Pluronics and HP-gamma-cyclodextrin. Studies of curcumin and curcuminoids, XLIV.

    PubMed

    Singh, R; Kristensen, S; Tønnesen, H H

    2012-02-01

    Curcumin was solubilized by Pluronics and the concentration of dissolved curcumin seemed to be related to the number of propylene oxide units in the Pluronic polymer. All Pluronics showed a maximum solubilizing capacity at a certain curcumin: Pluronic molar ratio and exceeding this molar ratio resulted in precipitation of curcumin when following the samples for 356 hours. PEG 400 could to a certain extent stabilize the supersaturated samples, while ethanol physically destabilized the samples. Ionic strength did not influence the solubilization of curcumin by the Pluronics. Supersaturation and precipitation inhibition caused a higher concentration of curcumin in samples prepared by SEM compared to samples prepared by SFM (i.e. the thermodynamic solubility). PMID:22512083

  19. Controlled release of curcumin from curcumin-loaded nanomicelles to prevent peritendinous adhesion during Achilles tendon healing in rats

    PubMed Central

    Zhang, Weizhong; Li, Xuanyi; Comes Franchini, Mauro; Xu, Ke; Locatelli, Erica; Martin, Robert C; Monaco, Ilaria; Li, Yan; Cui, Shusen

    2016-01-01

    We introduced curcumin-loaded nanomicelles into a tendon-healing model to evaluate their effects on tendon healing and adhesion. Three groups consisting of 36 rats underwent rupture and repair of the Achilles tendon. The treatment group received an injection of curcumin-loaded nanomicelles (gold nanorods [GNRs]-1/curcumin in polymeric nanomicelles [curc@PMs] at a dosage of 0.44 mg curcumin/kg in 0.1 mL saline) into the surgical site and exposed to laser postoperatively at weeks 1, 2, and 3, for three times 10 seconds each, on the surgical site in the rats that underwent tendon rupture and repair, while the other two groups received 0.44 mg curcumin/kg in 0.1 mL saline and 0.1 mL of saline, respectively. The specimens were harvested at 4 weeks and subjected to biomechanical and histological evaluation. The scoring results of tendon adhesion indicated that GNRs-1/curc@PMs group was in the lowest grade of peritendinous adhesions compared to the other groups. Histological assessment further confirmed the preventive effect of GNRs-1/curc@PMs on tendon adhesion. These findings indicated greater tendon strength with less adhesion in the group treated with GNRs-1/curc@PMs combined with laser exposure, and that nanoparticle-based therapy may be applied to prevent adhesion in clinical patients. PMID:27382278

  20. Curcumin enhances poly(ADP-ribose) polymerase inhibitor sensitivity to chemotherapy in breast cancer cells.

    PubMed

    Choi, Young Eun; Park, Eunmi

    2015-12-01

    Poly(ADP-ribose) polymerase (PARP) inhibitor has shown promising responses in homologous recombination (HR) repair-deficient cancer cells. More specifically, targeting HR pathway in combination with PARP inhibitor has been an effective chemotherapy strategy by so far. Curcumin has been recognized as anticancer agents for several types of cancers. Here, we demonstrate that curcumin inhibits a critical step in HR pathway, Rad51 foci formation, and accumulates γ-H2AX levels in MDA-MB-231 breast cancer cells. Curcumin also directly reduces HR and induces cell death with cotreatment of PARP inhibitor in MDA-MB-231 breast cancer cells. Moreover, curcumin, when combined with ABT-888, could effectively delayed breast tumor formation in vivo. Our study indicates that cotreatment of curcumin and PARP inhibitor might be useful for the combination chemotherapy for aggressive breast cancer treatment as a natural bioactive compound. PMID:26350251

  1. Curcumin: a natural substance with potential efficacy in Alzheimer’s disease

    PubMed Central

    Potter, Pamela E

    2013-01-01

    Curcumin is a component of turmeric, a spice used in many types of cooking. Epidemiological evidence suggesting that populations that eat food with a substantial amount of curcumin were at lower risk of Alzheimer’s disease (AD) led to the idea that this compound might have a neuroprotective effect. Curcumin has substantial antioxidant and anti-inflammatory effects, and is being used as a potential preventative agent or treatment for many types of cancer. There is evidence to suggest that the addition of curcumin to cultured neuronal cells decreases brain inflammation and protects against β-amyloid-induced neurotoxicity. Curcumin also protects against toxicity when β-amyloid is administered to produce animal models of AD. Curcumin decreases β-amyloid formation from amyloid precursor protein, and also inhibits aggregation of β-amyloid into pleated sheets. Studies in transgenic mice with overproduction of β-amyloid demonstrate a neuroprotective effect of curcumin as well. Cognitive function was also improved in these animal models. Clinical trials of curcumin in AD have not been very promising. It is possible that this is due to poor oral bioavailability of curcumin in humans, and thus several approaches are being developed to improve delivery systems or to create analogs that will mimic the neuroprotective effects and easily reach the brain. The lack of efficacy of curcumin in humans with AD may also result from treating for too short a time or starting treatment too late in the course of the disease, where substantial neuronal death has already occurred and cannot be reversed. Curcumin may be beneficial in protecting against development or progression of AD if taken over the long term and started before symptoms of AD become apparent. PMID:27186134

  2. Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells.

    PubMed

    Du, Qin; Hu, Bing; An, Hong-Mei; Shen, Ke-Ping; Xu, Ling; Deng, Shan; Wei, Meng-Meng

    2013-05-01

    Hepatocellular carcinoma remains one of the most prevalent malignancies worldwide. Curcuma aromatica and Polygonum cuspidatum are one of the commonly used paired-herbs for liver cancer treatment. Curcumin and resveratrol are the major anticancer constituents of Curcuma aromatica and Polygonum cuspidatum, respectively. Curcumin and resveratrol have been found to exhibit a synergistic anticancer effect in colon cancer. However, the combined effect of curcumin and resveratrol against hepatocellular carcinoma remains unknown. In the present study, we evaluated the combined effects of curcumin and resveratrol in hepatocellular carcinoma Hepa1-6 cells. The results showed that curcumin and resveratrol significantly inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner. The combination treatment of curcumin and resveratrol elicited a synergistic antiproliferative effect in Hepa1-6 cells. The apoptosis of Hepa1-6 cells induced by the combination treatment with curcumin and resveratrol was accompanied by caspase-3, -8 and -9 activation, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. Combination of curcumin and resveratrol upregulated intracellular reactive oxygen species (ROS) levels in Hepa1-6 cells. The ROS scavenger, NAC, partially attenuated the apoptosis and caspase activation induced by the combination treatment of curcumin and resveratrol. In addition, the combination of curcumin and resveratrol downregulated XIAP and survivin expression. These data suggest that the combination treatment of curcumin and resveratrol is a promising novel anticancer strategy for liver cancer. The present study also provides new insights into the effective mechanism of paired-herbs in traditional Chinese medicine. PMID:23446753

  3. Efficient inhibition of ovarian cancer by degradable nanoparticle-delivered survivin T34A gene

    PubMed Central

    Luo, Li; Du, Ting; Zhang, Jiumeng; Zhao, Wei; Cheng, Hao; Yang, Yuping; Wu, Yujiao; Wang, Chunmei; Men, Ke; Gou, Maling

    2016-01-01

    Gene therapy has promising applications in ovarian cancer therapy. Blocking the function of the survivin protein could lead to the growth inhibition of cancer cells. Herein, we used degradable heparin–polyethyleneimine (HPEI) nanoparticles to deliver a dominant-negative human survivin T34A (hs-T34A) gene to treat ovarian cancer. HPEI nanoparticles were characterized and were found to have a dynamic diameter of 66±4.5 nm and a zeta potential of 27.1±1.87 mV. The constructed hs-T34A gene expression plasmid could be effectively delivered into SKOV3 ovarian carcinoma cells by HPEI nanoparticles with low cytotoxicity. Intraperitoneal administration of HPEI/hs-T34A complexes could markedly inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. Moreover, according to our results, apparent apoptosis of cancer cells was observed both in vitro and in vivo. Taken together, the prepared HPEI/hs-T34A formulation showed potential applications in ovarian cancer gene therapy. PMID:26893558

  4. Efficient inhibition of ovarian cancer by degradable nanoparticle-delivered survivin T34A gene.

    PubMed

    Luo, Li; Du, Ting; Zhang, Jiumeng; Zhao, Wei; Cheng, Hao; Yang, Yuping; Wu, Yujiao; Wang, Chunmei; Men, Ke; Gou, Maling

    2016-01-01

    Gene therapy has promising applications in ovarian cancer therapy. Blocking the function of the survivin protein could lead to the growth inhibition of cancer cells. Herein, we used degradable heparin-polyethyleneimine (HPEI) nanoparticles to deliver a dominant-negative human survivin T34A (hs-T34A) gene to treat ovarian cancer. HPEI nanoparticles were characterized and were found to have a dynamic diameter of 66±4.5 nm and a zeta potential of 27.1±1.87 mV. The constructed hs-T34A gene expression plasmid could be effectively delivered into SKOV3 ovarian carcinoma cells by HPEI nanoparticles with low cytotoxicity. Intraperitoneal administration of HPEI/hs-T34A complexes could markedly inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. Moreover, according to our results, apparent apoptosis of cancer cells was observed both in vitro and in vivo. Taken together, the prepared HPEI/hs-T34A formulation showed potential applications in ovarian cancer gene therapy. PMID:26893558

  5. Curcumin Protects Neonatal Rat Cardiomyocytes against High Glucose-Induced Apoptosis via PI3K/Akt Signalling Pathway

    PubMed Central

    Yu, Wei; Zha, Wenliang; Ke, Zhiqiang; Min, Qing; Li, Cairong; Sun, Huirong; Liu, Chao

    2016-01-01

    The function of curcumin on NADPH oxidase-related ROS production and cardiac apoptosis, together with the modulation of protein signalling pathways, was investigated in cardiomyocytes. Primary cultures of neonatal rat cardiomyocytes were exposed to 30 mmol/L high glucose with or without curcumin. Cell viability, apoptosis, superoxide formation, the expression of NADPH oxidase subunits, and potential regulatory molecules, Akt and GSK-3β, were assessed in cardiomyocytes. Cardiomyocytes exposure to high glucose led to an increase in both cell apoptosis and intracellular ROS levels, which were strongly prevented by curcumin treatment (10 μM). In addition, treatment with curcumin remarkably suppressed the increased activity of Rac1, as well as the enhanced expression of gp91phox and p47phox induced by high glucose. Lipid peroxidation and SOD were reversed in the presence of curcumin. Furthermore, curcumin treatment markedly inhibited the reduced Bcl-2/Bax ratio elicited by high glucose exposure. Moreover, curcumin significantly increased Akt and GSK-3β phosphorylation in cardiomyocytes treated with high glucose. In addition, LY294002 blocked the effects of curcumin on cardiomyocytes exposure to high glucose. In conclusion, these results demonstrated that curcumin attenuated high glucose-induced cardiomyocyte apoptosis by inhibiting NADPH-mediated oxidative stress and this protective effect is most likely mediated by PI3K/Akt-related signalling pathway. PMID:26989696

  6. Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

    PubMed

    Waghela, Bhargav N; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M; Pathak, Chandramani

    2015-01-01

    Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

  7. Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application.

    PubMed

    Kalita, Himani; Prashanth Kumar, B N; Konar, Suraj; Tantubay, Sangeeta; Kr Mahto, Madhusudan; Mandal, Mahitosh; Pathak, Amita

    2016-03-01

    The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~48 nm and 206.51 m(2)/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin. PMID:26706510

  8. Metal complexes of curcumin for cellular imaging, targeting, and photoinduced anticancer activity.

    PubMed

    Banerjee, Samya; Chakravarty, Akhil R

    2015-07-21

    Curcumin is a polyphenolic species. As an active ingredient of turmeric, it is well-known for its traditional medicinal properties. The therapeutic values include antioxidant, anti-inflammatory, antiseptic, and anticancer activity with the last being primarily due to inhibition of the transcription factor NF-κB besides affecting several biological pathways to arrest tumor growth and its progression. Curcumin with all these positive qualities has only remained a potential candidate for cancer treatment over the years without seeing any proper usage because of its hydrolytic instability involving the diketo moiety in a cellular medium and its poor bioavailability. The situation has changed considerably in recent years with the observation that curcumin in monoanionic form could be stabilized on binding to a metal ion. The reports from our group and other groups have shown that curcumin in the metal-bound form retains its therapeutic potential. This has opened up new avenues to develop curcumin-based metal complexes as anticancer agents. Zinc(II) complexes of curcumin are shown to be stable in a cellular medium. They display moderate cytotoxicity against prostate cancer and neuroblastoma cell lines. A similar stabilization and cytotoxic effect is reported for (arene)ruthenium(II) complexes of curcumin against a variety of cell lines. The half-sandwich 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane (RAPTA)-type ruthenium(II) complexes of curcumin are shown to be promising cytotoxic agents with low micromolar concentrations for a series of cancer cell lines. In a different approach, cobalt(III) complexes of curcumin are used for its cellular delivery in hypoxic tumor cells using intracellular agents that reduce the metal and release curcumin as a cytotoxin. Utilizing the photophysical and photochemical properties of the curcumin dye, we have designed and synthesized photoactive curcumin metal complexes that are used for cellular imaging by fluorescence microscopy and

  9. Intrathecal curcumin attenuates pain hypersensitivity and decreases spinal neuroinflammation in rat model of monoarthritis.

    PubMed

    Chen, Jun-Jie; Dai, Lin; Zhao, Lin-Xia; Zhu, Xiang; Cao, Su; Gao, Yong-Jing

    2015-01-01

    Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund's adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain. PMID:25988362

  10. Expression profile of genes regulated by curcumin in Y79 retinoblastoma cells.

    PubMed

    Sreenivasan, Seethalakshmi; Thirumalai, Karthiyaini; Krishnakumar, Subramanian

    2012-01-01

    Curcumin, a well-known chemopreventive agent from turmeric, inhibits the expression of several oncogenes and cell proliferation genes in tumor cells. This study aims to understand the precise molecular mechanism by which curcumin exerts its effects on retinoblastoma cells, by performing whole genome microarray analysis to determine the gene expression profiles altered by curcumin treatment. Curcumin suppressed cell viability and altered the cell cycle of retinoblastoma cells. We identified 903 downregulated genes and 1,319 upregulated genes when compared with the control cells after treatment with 20 μM curcumin concentration for 48 h. These genes were grouped into respective functional categories according to their biological function. We found that curcumin regulated the expression of genes that are involved in the regulation of apoptosis, tumor suppressor, cell-cycle arrest, transcription factor, and angiogenesis. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to validate the results of genome array, and the results were consistent with the obtained data. In conclusion, treatment of curcumin affects the expression of genes involved in various cellular functions and plays an important role in tumor metastasis and apoptosis. Thus, curcumin might be an effective chemopreventive agent for retinoblastoma cancer. PMID:22489823

  11. Activation of PPARγ/P53 signaling is required for curcumin to induce hepatic stellate cell senescence

    PubMed Central

    Jin, H; Lian, N; Zhang, F; Chen, L; Chen, Q; Lu, C; Bian, M; Shao, J; Wu, L; Zheng, S

    2016-01-01

    Activation of quiescent hepatic stellate cells (HSCs) is the major event in hepatic fibrogenesis, along with enhancement of cell proliferation and overproduction of extracellular matrix. Although inhibition of cell proliferation and induction of apoptosis are potential strategies to block the activation of HSCs, a better understanding of the senescence of activated HSCs can provide a new therapeutic strategy for prevention and treatment of liver fibrosis. The antioxidant curcumin, a phytochemical from turmeric, has been shown to suppress HSC activation in vitro and in vivo. The current work was aimed to evaluate the effect of curcumin on senescence of activated HSCs and to elucidate the underlying mechanisms. In this study, curcumin promoted the expression of senescence marker Hmga1 in rat fibrotic liver. In addition, curcumin increased the number of senescence-associated β-galactosidase-positive HSCs in vitro. At the same time, curcumin induced HSC senescence by elevating the expression of senescence markers P16, P21 and Hmga1, concomitant with reduced abundance of HSC activation markers α-smooth muscle actin and α1(I)-procollagen in cultured HSCs. Moreover, curcumin affected the cell cycle and telomerase activity. We further demonstrated that P53 pharmacological inhibitor pifithrin-α (PFT-α) or transfection with P53 siRNA abrogated the curcumin-induced HSC senescence in vitro. Meanwhile, curcumin disruption of P53 leading to increased senescence of activated HSCs was further verified in vivo. Further studies indicated that curcumin promoted the expression of P53 through a PPARγ activation-dependent mechanism. Moreover, promoting PPARγ transactivating activity by a PPARγ agonist 15d-PGJ2 markedly enhanced curcumin induction of senescence of activated HSCs. However, the PPARγ antagonist PD68235 eliminated curcumin induction of HSC senescence. Taken together, our results provided a novel insight into the mechanisms underlying curcumin inhibition of HSC

  12. Activation of PPARγ/P53 signaling is required for curcumin to induce hepatic stellate cell senescence.

    PubMed

    Jin, H; Lian, N; Zhang, F; Chen, L; Chen, Q; Lu, C; Bian, M; Shao, J; Wu, L; Zheng, S

    2016-01-01

    Activation of quiescent hepatic stellate cells (HSCs) is the major event in hepatic fibrogenesis, along with enhancement of cell proliferation and overproduction of extracellular matrix. Although inhibition of cell proliferation and induction of apoptosis are potential strategies to block the activation of HSCs, a better understanding of the senescence of activated HSCs can provide a new therapeutic strategy for prevention and treatment of liver fibrosis. The antioxidant curcumin, a phytochemical from turmeric, has been shown to suppress HSC activation in vitro and in vivo. The current work was aimed to evaluate the effect of curcumin on senescence of activated HSCs and to elucidate the underlying mechanisms. In this study, curcumin promoted the expression of senescence marker Hmga1 in rat fibrotic liver. In addition, curcumin increased the number of senescence-associated β-galactosidase-positive HSCs in vitro. At the same time, curcumin induced HSC senescence by elevating the expression of senescence markers P16, P21 and Hmga1, concomitant with reduced abundance of HSC activation markers α-smooth muscle actin and α1(I)-procollagen in cultured HSCs. Moreover, curcumin affected the cell cycle and telomerase activity. We further demonstrated that P53 pharmacological inhibitor pifithrin-α (PFT-α) or transfection with P53 siRNA abrogated the curcumin-induced HSC senescence in vitro. Meanwhile, curcumin disruption of P53 leading to increased senescence of activated HSCs was further verified in vivo. Further studies indicated that curcumin promoted the expression of P53 through a PPARγ activation-dependent mechanism. Moreover, promoting PPARγ transactivating activity by a PPARγ agonist 15d-PGJ2 markedly enhanced curcumin induction of senescence of activated HSCs. However, the PPARγ antagonist PD68235 eliminated curcumin induction of HSC senescence. Taken together, our results provided a novel insight into the mechanisms underlying curcumin inhibition of HSC

  13. Silver nanoparticles inhibit fish gill cell proliferation in protein-free culture medium.

    PubMed

    Yue, Yang; Behra, Renata; Sigg, Laura; Schirmer, Kristin

    2016-10-01

    While short-term exposures of vertebrate cells, such as from fish, can be performed in defined, serum-free media, long-term cultures generally require addition of growth factors and proteins, normally supplied with a serum supplement. However, proteins are known to alter nanoparticle properties by binding to nanoparticles. Therefore, in order to be able to study nanoparticle-cell interactions for extended periods, the rainbow trout (Oncorhynchus mykiss) gill cell line, RTgill-W1, was adapted to proliferate in a commercial, serum-free medium, InVitrus VP-6. The newly adapted cell strain was named RTgill-W1-pf (protein free). These cells proliferate at a speed similar to the RTgill-W1 cells cultured in a fully supplemented medium containing 5% fetal bovine serum. As well, they were successfully cryopreserved in liquid nitrogen and fully recovered after thawing. Yet, senescence set in after about 10 passages in InVitrus VP-6 medium, revealing that this medium cannot fully support long-term culture of the RTgill-W1 strain. The RTgill-W1-pf cell line was subsequently applied to investigate the effect of silver nanoparticles (AgNP) on cell proliferation over a period of 12 days. Indeed, cell proliferation was inhibited by 10 μM AgNP. This effect correlated with high levels of silver being associated with the cells. The new cell line, RTgill-W1-pf, can serve as a unique representation of the gill cell-environment interface, offering novel opportunities to study nanoparticle-cell interactions without serum protein interference. PMID:27030289

  14. Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis.

    PubMed

    Wang, Yuji; Tang, Jingcheng; Zhu, Haimei; Jiang, Xueyun; Liu, Jiawang; Xu, Wenyun; Ma, Haiping; Feng, Qiqi; Wu, Jianhui; Zhao, Ming; Peng, Shiqi

    2015-01-01

    The hot water extract of Rabdosia rubescens was traditionally used as an antithrombotic medicine. To explore its antithrombotic utility and mechanism, we carried out a series of in vitro and in vivo assays in this study. In vitro platelet aggregation assay showed that the half maximal inhibitory concentration values of aqueous extract of R. rubescens leaves (AERL) inhibiting platelet aggregation induced by thrombin, arachidonic acid, adenosine diphosphate, and platelet-activating factor ranged from 0.12 mg/mL to 1.43 mg/mL. The minimal effective oral dose of AERL inhibiting the rats from forming thrombus was 25 mg/kg. Both in vitro and in vivo actions were correlated with AERL concentration-dependently inhibiting sP-selectin release. In water, AERL formed nanoparticles, and their size depended on the concentration. Docking the five nucleotides, 21 phenolic acids, and four diterpenoids identified by high-performance liquid chromatography-photodiode array detector/(-)electrospray ionization-tandem mass spectrometry analysis into the active site of P-selectin, rosmarinic acid was predicted to be the antithrombotic ingredient of AERL. In flow cytometry analysis, 1 μM of rosmarinic acid effectively inhibited sP-selectin release in arachidonic acid-activated platelets. In a rat model, 5 mg/kg of oral rosmarinic acid effectively inhibited thrombosis. PMID:26604756

  15. Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis

    PubMed Central

    Wang, Yuji; Tang, Jingcheng; Zhu, Haimei; Jiang, Xueyun; Liu, Jiawang; Xu, Wenyun; Ma, Haiping; Feng, Qiqi; Wu, Jianhui; Zhao, Ming; Peng, Shiqi

    2015-01-01

    The hot water extract of Rabdosia rubescens was traditionally used as an antithrombotic medicine. To explore its antithrombotic utility and mechanism, we carried out a series of in vitro and in vivo assays in this study. In vitro platelet aggregation assay showed that the half maximal inhibitory concentration values of aqueous extract of R. rubescens leaves (AERL) inhibiting platelet aggregation induced by thrombin, arachidonic acid, adenosine diphosphate, and platelet-activating factor ranged from 0.12 mg/mL to 1.43 mg/mL. The minimal effective oral dose of AERL inhibiting the rats from forming thrombus was 25 mg/kg. Both in vitro and in vivo actions were correlated with AERL concentration-dependently inhibiting sP-selectin release. In water, AERL formed nanoparticles, and their size depended on the concentration. Docking the five nucleotides, 21 phenolic acids, and four diterpenoids identified by high-performance liquid chromatography–photodiode array detector/(−)electrospray ionization-tandem mass spectrometry analysis into the active site of P-selectin, rosmarinic acid was predicted to be the antithrombotic ingredient of AERL. In flow cytometry analysis, 1 μM of rosmarinic acid effectively inhibited sP-selectin release in arachidonic acid-activated platelets. In a rat model, 5 mg/kg of oral rosmarinic acid effectively inhibited thrombosis. PMID:26604756

  16. Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy.

    PubMed

    Ramasamy, Thamil Selvee; Ayob, Ain Zubaidah; Myint, Hsu Hsu Lynn; Thiagarajah, Sharmanee; Amini, Farahnaz

    2015-01-01

    Colorectal cancer is one of the commonest cancers in the world and it is also a common cause of cancer-related death worldwide. Despite advanced treatment strategies, the disease is rarely cured completely due to recurrence. Evidence shows that this is due to a small population of cells, called cancer stem cells (CSCs), in the tumour mass that have the self-renewal and differentiation potential to give rise to a new tumour population. Many pre-clinical and clinical studies have used curcumin and its analogues as anti-cancer agents in various types of cancer, including colorectal cancer. Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth. In this review, we highlight the efficacy of curcumin and its analogues in targeting colorectal CSC and also the underlying molecular mechanism involved. Curcumin, in the presence or absence of other anti-cancer agents, has been shown to reduce the size of tumour mass and growth in both in vivo and in vitro studies by affecting many intracellular events that are associated with cancer progression and CSC formation. An insight into the molecular mechanism has unraveled the mode of action via which curcumin could affect the key regulators in CSC, importantly; (1) the signaling pathways, including Wnt/β-catenin, Sonic Hedgehog, Notch and PI3K/Akt/mTOR, (2) microRNA and (3) the epithelial-mesenchymal transition at multiple levels. Therefore, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy, therefore, combination therapy using anti-cancer agent with curcumin could be much more effective than treatment using a single cancer agent. This potential treatment modality can be further developed by employing an effective delivery system using a nanotechnology based approach to treat colorectal cancer. PMID:26457069

  17. Curcumin and cancer: barriers to obtaining a health claim.

    PubMed

    Devassy, Jessay G; Nwachukwu, Ifeanyi D; Jones, Peter J H

    2015-03-01

    Curcumin is a highly pleiotropic molecule found in the rhizomes of Curcuma longa (turmeric). It is responsible for the yellow color of turmeric and has been shown to inhibit the proliferation of cancer cells and to be of use in preventing or treating a number of diseases. Curcumin has been shown to modulate multiple cell-signaling pathways simultaneously, thereby mitigating or preventing many different types of cancers, including multiple myeloma and colorectal, pancreatic, breast, prostate, lung, head, and neck cancers, in both animal models and humans. Current therapeutic approaches using a single cancer drug for a single target can be expensive, have serious side effects, or both. Consequently, new approaches to the treatment and prevention of cancer, including the integration of curcumin as a viable treatment strategy where dysregulation of many pathways is involved, are warranted. A methodical review of the evidence was performed to evaluate the effects of curcumin in support of a health claim, as established through the regulatory framework of Health Canada, for a relationship between the consumption of curcumin and the prevention and treatment of cancer. PMID:26024538

  18. HSP60 mediates the neuroprotective effects of curcumin by suppressing microglial activation

    PubMed Central

    Ding, Feijia; Li, Fan; Li, Yunhong; Hou, Xiaolin; Ma, Yi; Zhang, Nan; Ma, Jiao; Zhang, Rui; Lang, Bing; Wang, Hongyan; Wang, Yin

    2016-01-01

    Curcumin has anti-inflammatory and antioxidant properties and has been widely used to treat or prevent neurodegenerative diseases. However, the mechanisms underlying the neuroprotective effects of curcumin are not well known. In the present study, the effect of curcumin on lipopolysaccharide (LPS)-stimulated BV2 mouse microglia cells was investigated using enzyme-linked immunosorbent assays of the culture medium and western blotting of cell lysates. The results showed that curcumin significantly inhibited the LPS-induced expression and release of heat shock protein 60 (HSP60) in the BV2 cells. The level of heat shock factor (HSF)-1 was upregulated in LPS-activated BV2 microglia, indicating that the increased expression of HSP60 was driven by HSF-1 activation. However, the increased HSF-1 level was downregulated by curcumin. Extracellular HSP60 is a ligand of Toll-like receptor 4 (TLR-4), and the level of the latter was increased in the LPS-activated BV2 microglia and inhibited by curcumin. The activation of TLR-4 is known to be associated with the activation of myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-κB, with the subsequent production of proinflammatory and neurotoxic factors. In the present study, curcumin demonstrated marked suppression of the LPS-induced expression of MyD88, NF-κB, caspase-3, inducible nitric oxide synthase, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the microglia. These results indicate that curcumin may exert its neuroprotective and anti-inflammatory effects by inhibiting microglial activation through the HSP60/TLR-4/MyD88/NF-κB signaling wpathway. Therefore, curcumin may be useful for the treatment of neurodegenerative diseases that are associated with microglial activation. PMID:27446282

  19. Curcumin and Health.

    PubMed

    Pulido-Moran, Mario; Moreno-Fernandez, Jorge; Ramirez-Tortosa, Cesar; Ramirez-Tortosa, Mcarmen

    2016-01-01

    Nowadays, there are some molecules that have shown over the years a high capacity to act against relevant pathologies such as cardiovascular disease, neurodegenerative disorders or cancer. This article provides a brief review about the origin, bioavailability and new research on curcumin and synthetized derivatives. It examines the beneficial effects on health, delving into aspects such as cancer, cardiovascular effects, metabolic syndrome, antioxidant capacity, anti-inflammatory properties, and neurological, liver and respiratory disorders. Thanks to all these activities, curcumin is positioned as an interesting nutraceutical. This is the reason why it has been subjected to several modifications in its structure and administration form that have permitted an increase in bioavailability and effectiveness against different diseases, decreasing the mortality and morbidity associated to these pathologies. PMID:26927041

  20. Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway

    SciTech Connect

    Zhang, Jian; Zhang, Tao; Ti, Xinyu; Shi, Jieran; Wu, Changgui; Ren, Xinling; Yin, Hong

    2010-08-13

    Research highlights: {yields} Curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells {yields} Curcumin promotes apoptosis in A549/DDP cells through a miRNA signaling pathway {yields} Curcumin induces A549/DDP cell apoptosis by downregulating miR-186* {yields} miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin -- Abstract: Curcumin extracted from the rhizomes of Curcuma longa L. has been shown to have inhibitory effects on cancers through its anti-proliferative and pro-apoptotic activities. Emerging evidence demonstrates that curcumin can overcome drug resistance to classical chemotherapies. Thus, the mechanisms underlying the anti-tumor activities of curcumin require further study. In our study, we first demonstrated that curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells. Further studies showed that curcumin altered miRNA expression; in particular, significantly downregulated the expression of miR-186* in A549/DDP. In addition, transfection of cells with a miR-186* inhibitor promoted A549/DDP apoptosis, and overexpression of miR-186* significantly inhibited curcumin-induced apoptosis in A549/DDP cells. These observations suggest that miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin.

  1. [Influence of curcumin--loaded poly (lactide-co-glycolide) films on the proliferation of vascular smooth muscle cells].

    PubMed

    Ren, Ling; Wang, Jin; Tang, Jiaju; Pan, Changjiang; Huang, Nan

    2008-08-01

    In-stent restenosis is the major problem of percutaneous coronary interventions. Drug-eluting stent became a landmark in the treatment of coronary disease. Curcumin could be used for drug-eluting stent due to its antithrombogenity and antiproliferative properties. In this paper, 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were performed to decide the optimal concentration of curcumin for inhibiting the proliferation of vascular smooth muscle cells (VSMC). The result disclosed that more than 80% of VSMC were inhibited when the concentration of curcumin ranged from 2.5 microg/ml to 10 microg/ml (P < 0.05, compared to ethanol). Three weight percent curcumin-loaded films (3wt%, 5wt%, 8wt%) were prepared using a biodegradable polymer (poly (lactic acid-co-glycol acid), PLGA) as the carrier of curcumin. The release of lactate dehydrogenase (LDH) was used to evaluate the immediate toxicity of the curcumin-loaded PLGA films, and the three concentration curcumin-loaded films were revealed to be of no acute toxicity to the smooth muscle cells. The results of Alamar Blue test indicated that the curcumin-loaded films had better antiproliferation effect than did the 316 stainless steel (SS). Therefore, these films may be used for stent coating to inhibit the in-stent restenosis induced by VSMC proliferation. PMID:18792454

  2. Optimised nano-formulation on the bioavailability of hydrophobic polyphenol, curcumin, in freely-moving rats.

    PubMed

    Tsai, Yin-Meng; Jan, Woan-Ching; Chien, Chao-Feng; Lee, Wen-Chuan; Lin, Lie-Chwen; Tsai, Tung-Hu

    2011-08-01

    This study has optimised the poly lactic-co-glycolic acid (PLGA) nano-formulation of curcumin to prolong its retention time in the body and improve bioavailability. High-pressure emulsification-solvent-evaporation was designed to obtain curcumin-loaded PLGA nanoparticles (C-NPs) prepared with 2% of PVA containing 20% sucrose as aqueous phase and dichloromethane as oil phase. The size and entrapment efficiency of C-NPs was 158±10nm and 46.6±13.5%, respectively. The stable storage time of C-NPs was one month at 4°C. When curcumin was formulated, a significant increase of curcumin exposure in rat plasma was revealed from the intravenous study (AUC/Dose raised 55%) and the oral study (AUC/Dose increased 21-fold). The oral bioavailability of curcumin at C-NPs was 22-fold higher than conventional curcumin. Excretion results support oral study that absorption of curcumin was significantly increased by nano-formulation. These findings demonstrate that PLGA nano-formulation could potentially be applied to increase bioavailability of hydrophobic polyphenols. PMID:25214079

  3. Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals.

    PubMed

    Farazuddin, Mohammad; Dua, Bhavyata; Zia, Qamar; Khan, Aijaz Ahmad; Joshi, Beenu; Owais, Mohammad

    2014-01-01

    Curcumin (diferuloylmethane) is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver. Unfortunately, the poor bioavailability and hydrophobicity of curcumin pose a major hurdle to its use as a potent anticancer agent. To circumvent some of these problems, we developed a novel, dual-core microcell formulation of curcumin. The encapsulation of curcumin in microcells increases its solubility and bioavailability, and facilitates slow release kinetics over extended periods. Besides being safe, these formulations do not bear any toxicity constraints, as revealed by in vitro and in vivo studies. Histopathological analysis revealed that curcumin-bearing microcells helped in regression of hepatocellular carcinoma and the maintenance of cellular architecture in liver tissue. Free curcumin had a very mild effect on cancer suppression. Empty (sham) microcells and microparticles failed to inhibit cancer cells. The novel curcumin formulation was found to suppress hepatocellular carcinoma efficiently in Swiss albino mice. PMID:24627632

  4. Curcumin lowers erlotinib resistance in non-small cell lung carcinoma cells with mutated EGF receptor.

    PubMed

    Li, Shanqun; Liu, Zilong; Zhu, Fen; Fan, Xiaohong; Wu, Xiaodan; Zhao, Heng; Jiang, Liyan

    2013-01-01

    Non-small cell lung cancer (NSCLC) patients with activating mutations in the epidermal growth factor receptor (EGFR) are responsive to erlotinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, patients with secondary somatic EGFR mutations are resistant to EGFR-TKI treatment. In this study, we investigated the effect of curcumin on the tumor growth of erlotinib-resistant NSCLC cells. Cell proliferation was determined by MTT assay. Apoptosis was examined using TUNEL staining. Protein expression of genes was determined by Western blot. Tumor growth was assessed in a xenograft mouse model. Results showed that erlotinib had a stronger effect on the induction of apoptosis in erlotinib-sensitive PC-9 cells but showed a weaker effect on erlotinib-resistant H1975 and H1650 cells than cisplatin and curcumin. Furthermore, curcumin significantly increased the cytotoxicity of erlotinib to erlotinib-resistant NSCLC cells, enhanced erlotinib-induced apoptosis, downregulated the expressions of EGFR, p-EGFR, and survivin, and inhibited the NF-κB activation in erlotinib-resistant NSCLC cells. The combination of curcumin and erlotinib exhibited the same effects on apoptosis as the combination of curcumin and cisplatin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of curcumin and erlotinib significantly inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo. Our results indicate that curcumin is a potential adjuvant for NSCLC patients during erlotinib treatment. PMID:24512728

  5. Chemiluminescence immunoassay using magnetic nanoparticles with targeted inhibition for the determination of ochratoxin A.

    PubMed

    Kim, Sumin; Lim, H B

    2015-08-01

    In this work, a chemiluminescence (CL) immunoassay with targeted inhibition was developed for the determination of toxins in food products. For sample treatment, amine-functionalized magnetic nanoparticles (MNPs) were synthesized to extract target molecules, and horseradish peroxidase (HRP) tagged on an antibody was used as a label for CL reaction. In particular, amine-targeted inhibition using aldehyde, i.e., specifically capping the amine with an alkyl group, was developed for a non-specific extraction platform to lower background and improve signal-to-background ratio. For demonstration, ochratoxin A (OTA) was determined in rice using a lab-built drop-type chemiluminescence (DCL) system with luminol-H2O2 reagent. The obtained limit of detection was 1.39 pg mL(-1), which was about 7.3 times better than that of ELISA. Recovery of the method in the range of 87-99% was observed, which was compared with ELISA. PMID:26048840

  6. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK.

    PubMed

    Li, Ying; Li, Jia; Li, Shanshan; Li, Yi; Wang, Xiangxiang; Liu, Baolin; Fu, Qiang; Ma, Shiping

    2015-07-01

    Curcumin is a natural polyphenolic compound in Curcuma longa with beneficial effects on neuronal protection. This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essential for the suppression of ER stress. As a result, curcumin reduced TXNIP expression and inhibited NLRP3 inflammasome activation by downregulation of NLRP3 and cleaved caspase-1 induction, and thus reduced IL-1β secretion. Specific fluorescent probe and flow cytometry analysis showed that curcumin prevented mitochondrial malfunction and protected cell survival from glutamate neurotoxicity. Moreover, oral administration of curcumin reduced brain infarct volume and attenuated neuronal damage in rats subjected to middle cerebral artery occlusion. Immunohistochemistry showed that curcumin inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region. Together, these results showed that curcumin attenuated glutamate neurotoxicity by inhibiting ER stress-associated TXNIP/NLRP3 inflammasome activation via the regulation of AMPK, and thereby protected the hippocampus from ischemic insult. PMID:25791922

  7. Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity.

    PubMed

    Bollimpelli, V Satish; Kumar, Prashant; Kumari, Sonali; Kondapi, Anand K

    2016-05-01

    Curcumin is known to have neuroprotective role and possess antioxidant, anti-inflammatory activities. Rotenone, a flavonoid induced neurotoxicity in dopaminergic cells is being widely studied in Parkinson's Disease (PD) research. In the present study, curcumin loaded lactoferrin nano particles prepared by sol-oil chemistry were used to protect dopaminergic cell line SK-N-SH against rotenone induced neurotoxicity. These curcumin loaded nano particles were of 43-60 nm diameter size and around 100 nm hydrodynamic size as assessed by transmission electron microscopy, atomic force microscopy and dynamic light scattering analysis respectively. The encapsulation efficiency was 61.3% ± 2.4%. Cellular uptake of curcumin through these nano particles was confirmed by confocal imaging and spectrofluorimetric analysis. The curcumin loaded lactoferrin nanoparticles showed greater intracellular drug uptake, sustained retention and greater neuroprotection than soluble counterpart. Neuroprotective activity was characterized through viability assays and by estimating ROS levels. Furthermore rotenone induced PD like features were characterized by decrease in tyrosine hydroxylase expression and increase in α-synuclein expression. Taken together curcumin loaded lactoferrin nanoparticles could be a promising drug delivery strategy against neurotoxicity in dopaminergic neurons. PMID:26826319

  8. Recent progress in studying curcumin and its nano-preparations for cancer therapy.

    PubMed

    Liu, Jieying; Chen, Siyuan; Lv, Li; Song, Lei; Guo, Shengrong; Huang, Shengtang

    2013-01-01

    A hydrophobic polyphenol compound extracted from turmeric, curcumin has been widely utilized as traditional medicines for centuries in China and India. Over the last decades, because of its low toxicity, extensive studies have been focused on its physicochemical properties and pharmacological activities on various diseases, such as cancer, cardio-vascular disease, inflammatory bowel, wound healing, Alzheimer's disease, rheumatoid arthritis, and diabetes. In particular, bioactivities of curcumin as an effective chemopreventive agent, chemo-/radio-sensitizer for tumor cells, and chemo-/radio-protector for normal organs, are of extraordinary research interests in the literature. Despite these advantages, applications of curcumin are limited in clinical trials because of its poor water solubility and low oral bioavailability. Nano-preparations as an emerging platform for the efficient delivery of anti-cancer drugs should overcome these problems. In this review, we at first briefly revisit important properties of curcumin as well as its uses in cancer treatments, and then overview various nano-preparations of curcumin for cancer therapy, including nanoparticles, liposomes, micelles, nanoemulsions, cyclodextrin complexes, nanodisks, nanofibres, solid lipid nanoparticles, and curcumin conjugates. PMID:23116308

  9. Effective protein inhibition in intact mouse oocytes through peptide nanoparticle-mediated antibody transfection

    PubMed Central

    Li, Ruichao; Jin, Zhen; Gao, Leilei; Liu, Peng

    2016-01-01

    Female meiosis is a fundamental area of study in reproductive medicine, and the mouse oocyte model of in vitro maturation (IVM) is most widely used to study female meiosis. To investigate the probable role(s) of an unknown protein in female meiosis, the method traditionally used involves microinjecting a specific antibody into mouse oocytes. Recently, in studies on somatic cells, peptide nanoparticle-mediated antibody transfection has become a popular tool because of its high efficiency, low toxicity, good stability, and strong serum compatibility. However, untill now no researchers have tried using this technique on mouse oocytes because the zona pellucida surrounding the oocyte membrane (vitelline membrane) is usually thought or proved to be a tough barrier to macromolecules such as antibodies and proteins. Therefore, we attempted to introduce an antibody into mouse oocytes using a peptide nanoparticle. Here we show for the first time that with our optimized method, an antibody can be effectively delivered into mouse oocytes and inhibit its target protein with high specificity. We obtained significant results using small GTPase Arl2 as a test subject protein. We propose peptide nanoparticle-mediated antibody transfection to be a superior alternative to antibody microinjection for preliminary functional studies of unknown proteins in mouse oocytes. PMID:27114861

  10. Synthesis of magnetic composite nanoparticles enveloped in copolymers specified for scale inhibition application

    NASA Astrophysics Data System (ADS)

    Do, Bao Phuong Huu; Dung Nguyen, Ba; Duy Nguyen, Hoang; Nguyen, Phuong Tung

    2013-12-01

    We report the synthesis of magnetic iron oxide nanoparticles encapsulated in maleic acid-2-acrylamido-2-methyl-1-propanesulfonate based polymer. This composite nanoparticle is specified for the high-pressure/high-temperature (HPHT) oilfield scale inhibition application. The process includes a facile-ultrasound-supported addition reaction to obtain iron oxide nanoparticles with surface coated by oleic acid. Then via inverse microemulsion polymerization with selected monomers, the specifically designed copolymers have been formatted in nanoscale. The structure and morphology of obtained materials were characterized by transmission electron microscopy (TEM), x-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the thermal stability. The effectiveness of synthesized compounds as a carbonate scale inhibitor was investigated by testing method NACE standard TM 03-074-95 at aging temperature of 70, 90 and 120 °C. The magnetic nanocomposite particles can be easily collected and detected demonstrating their superior monitoring ability, which is absent in the case of conventional copolymer-based scale inhibitor.

  11. Inhibition of E. coli and S. aureus with selenium nanoparticles synthesized by pulsed laser ablation in deionized water.

    PubMed

    Guisbiers, G; Wang, Q; Khachatryan, E; Mimun, L C; Mendoza-Cruz, R; Larese-Casanova, P; Webster, T J; Nash, K L

    2016-01-01

    Nosocomial diseases are mainly caused by two common pathogens, Escherichia coli and Staphylococcus aureus, which are becoming more and more resistant to conventional antibiotics. Therefore, it is becoming increasingly necessary to find other alternative treatments than commonly utilized drugs. A promising strategy is to use nanomaterials such as selenium nanoparticles. However, the ability to produce nanoparticles free of any contamination is very challenging, especially for nano-medical applications. This paper reports the successful synthesis of pure selenium nanoparticles by laser ablation in water and determines the minimal concentration required for ~50% inhibition of either E. coli or S. aureus after 24 hours to be at least ~50 ppm. Total inhibition of E. coli and S. aureus is expected to occur at 107±12 and 79±4 ppm, respectively. In this manner, this study reports for the first time an easy synthesis process for creating pure selenium to inhibit bacterial growth. PMID:27563240

  12. Inhibition of E. coli and S. aureus with selenium nanoparticles synthesized by pulsed laser ablation in deionized water

    PubMed Central

    Guisbiers, G; Wang, Q; Khachatryan, E; Mimun, LC; Mendoza-Cruz, R; Larese-Casanova, P; Webster, TJ; Nash, KL

    2016-01-01

    Nosocomial diseases are mainly caused by two common pathogens, Escherichia coli and Staphylococcus aureus, which are becoming more and more resistant to conventional antibiotics. Therefore, it is becoming increasingly necessary to find other alternative treatments than commonly utilized drugs. A promising strategy is to use nanomaterials such as selenium nanoparticles. However, the ability to produce nanoparticles free of any contamination is very challenging, especially for nano-medical applications. This paper reports the successful synthesis of pure selenium nanoparticles by laser ablation in water and determines the minimal concentration required for ~50% inhibition of either E. coli or S. aureus after 24 hours to be at least ~50 ppm. Total inhibition of E. coli and S. aureus is expected to occur at 107±12 and 79±4 ppm, respectively. In this manner, this study reports for the first time an easy synthesis process for creating pure selenium to inhibit bacterial growth. PMID:27563240

  13. Inhibition of gold nanoparticles (AuNPs) on pathogenic biofilm formation and invasion to host cells.

    PubMed

    Yu, Qilin; Li, Jianrong; Zhang, Yueqi; Wang, Yufan; Liu, Lu; Li, Mingchun

    2016-01-01

    Owing to the growing infectious diseases caused by eukaryotic and prokaryotic pathogens, it is urgent to develop novel antimicrobial agents against clinical pathogenic infections. Biofilm formation and invasion into the host cells are vital processes during pathogenic colonization and infection. In this study, we tested the inhibitory effect of Au nanoparticles (AuNPs) on pathogenic growth, biofilm formation and invasion. Interestingly, although the synthesized AuNPs had no significant toxicity to the tested pathogens, Candida albicans and Pseudomonas aeruginosa, the nanoparticles strongly inhibited pathogenic biofilm formation and invasion to dental pulp stem cells (DPSCs). Further investigations revealed that AuNPs abundantly bound to the pathogen cells, which likely contributed to their inhibitory effect on biofilm formation and invasion. Moreover, treatment of AuNPs led to activation of immune response-related genes in DPSCs, which may enhance the activity of host immune system against the pathogens. Zeta potential analysis and polyethylene glycol (PEG)/polyethyleneimine (PEI) coating tests further showed that the interaction between pathogen cells and AuNPs is associated with electrostatic attractions. Our findings shed novel light on the application of nanomaterials in fighting against clinical pathogens, and imply that the traditional growth inhibition test is not the only way to evaluate the drug effect during the screening of antimicrobial agents. PMID:27220400

  14. Inhibition of gold nanoparticles (AuNPs) on pathogenic biofilm formation and invasion to host cells

    PubMed Central

    Yu, Qilin; Li, Jianrong; Zhang, Yueqi; Wang, Yufan; Liu, Lu; Li, Mingchun

    2016-01-01

    Owing to the growing infectious diseases caused by eukaryotic and prokaryotic pathogens, it is urgent to develop novel antimicrobial agents against clinical pathogenic infections. Biofilm formation and invasion into the host cells are vital processes during pathogenic colonization and infection. In this study, we tested the inhibitory effect of Au nanoparticles (AuNPs) on pathogenic growth, biofilm formation and invasion. Interestingly, although the synthesized AuNPs had no significant toxicity to the tested pathogens, Candida albicans and Pseudomonas aeruginosa, the nanoparticles strongly inhibited pathogenic biofilm formation and invasion to dental pulp stem cells (DPSCs). Further investigations revealed that AuNPs abundantly bound to the pathogen cells, which likely contributed to their inhibitory effect on biofilm formation and invasion. Moreover, treatment of AuNPs led to activation of immune response-related genes in DPSCs, which may enhance the activity of host immune system against the pathogens. Zeta potential analysis and polyethylene glycol (PEG)/polyethyleneimine (PEI) coating tests further showed that the interaction between pathogen cells and AuNPs is associated with electrostatic attractions. Our findings shed novel light on the application of nanomaterials in fighting against clinical pathogens, and imply that the traditional growth inhibition test is not the only way to evaluate the drug effect during the screening of antimicrobial agents. PMID:27220400

  15. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

    NASA Astrophysics Data System (ADS)

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  16. Zinc oxide nanoparticle suspensions and layer-by-layer coatings inhibit staphylococcal growth.

    PubMed

    McGuffie, Matthew J; Hong, Jin; Bahng, Joong Hwan; Glynos, Emmanouil; Green, Peter F; Kotov, Nicholas A; Younger, John G; VanEpps, J Scott

    2016-01-01

    Despite a decade of engineering and process improvements, bacterial infection remains the primary threat to implanted medical devices. Zinc oxide nanoparticles (ZnO-NPs) have demonstrated antimicrobial properties. Their microbial selectivity, stability, ease of production, and low cost make them attractive alternatives to silver NPs or antimicrobial peptides. Here we sought to (1) determine the relative efficacy of ZnO-NPs on planktonic growth of medically relevant pathogens; (2) establish the role of bacterial surface chemistry on ZnO-NP effectiveness; (3) evaluate NP shape as a factor in the dose-response; and (4) evaluate layer-by-layer (LBL) ZnO-NP surface coatings on biofilm growth. ZnO-NPs inhibited bacterial growth in a shape-dependent manner not previously seen or predicted. Pyramid shaped particles were the most effective and contrary to previous work, larger particles were more effective than smaller particles. Differential susceptibility of pathogens may be related to their surface hydrophobicity. LBL ZnO-NO coatings reduced staphylococcal biofilm burden by >95%. From the Clinical Editor: The use of medical implants is widespread. However, bacterial colonization remains a major concern. In this article, the authors investigated the use of zinc oxide nanoparticles (ZnO-NPs) to prevent bacterial infection. They showed in their experiments that ZnO-NPs significantly inhibited bacterial growth. This work may present a new alternative in using ZnO-NPs in medical devices. PMID:26515755

  17. A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation

    PubMed Central

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S.G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J.M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show this effect is mediated through inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show they accumulate in atherosclerotic lesions where they directly affect plaque macrophages. Finally we demonstrate that a three-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a one-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation. PMID:24445279

  18. Effect of Curcumin on Pro-angiogenic Factors in the Xenograft Model of Breast Cancer.

    PubMed

    Ferreira, Livia Carvalho; Arbab, Ali S; Jardim-Perassi, Bruna Victorasso; Borin, Thaiz Ferraz; Varma, Nadimpalli R S; Iskander, A S M; Shankar, Adarsh; Ali, Meser M; Zuccari, Debora Aparecida Pires de Campos

    2015-01-01

    The formation of a new blood vessel is stimulated by angiogenic factors. Curcumin, which is the active ingredient of the spice plant Curcuma longa L and is used as food and traditional medicine, has shown anticancer effects against different types of cancers. We evaluated the effects of curcumin on angiogenesis/pro-angiogenic factors in a mouse model of human breast cancer. Cell viability was measured by the MTT assay after curcumin treatment in triple-negative breast cancer cells (MDA-MB-231). For the in vivo study, human breast cancer was induced in athymic mice and treated with 300 mg/kg/day of curcumin administered intraperitoneally. Tumor size was measured weekly, and the animals underwent single photon emission computed tomography (SPECT) scanning with Tc-99m tagged VEGF-c to detect the in vivo expression of VEGFR2/3. In addition, the expression of proangiogenic/ growth factors in the tumor extracts was evaluated by a membrane antibody array. Histological analysis was performed to confirm the effect of curcumin on neovascularization. The MTT assay showed that curcumin significantly reduced the cell viability of MDA-MB-231 cells. In breast cancer xenografts, curcumin treatment led to a decrease in tumor volume and cell proliferation (Ki-67) compared with the vehicle treated group. Tc-99m-HYNIC-VEGF-c-SPECT imaging showed decreased uptake to the tumor, which may indicate a lower expression of VEGFR2/3 in curcumin treated tumors; however, a statistically significant difference was not achieved (p>0.05). Additionally, curcumin treatment showed a significantly low level of expression of pro-angiogenic factors (p<0.05) and a decrease in micro-vessel density (vWF) in animals compared with that of vehicle treated tumors. In conclusion, curcumin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis. PMID:25991545

  19. Oxidative stress-mediated inhibition of intestinal epithelial cell proliferation by silver nanoparticles.

    PubMed

    McCracken, Christie; Zane, Andrew; Knight, Deborah A; Hommel, Elizabeth; Dutta, Prabir K; Waldman, W James

    2015-10-01

    Given the increasing use of silver nanoparticles (Ag NP) by the food and food packaging industries, this study investigated potential consequences of Ag NP ingestion in intestinal epithelial C2BBe1 cells. Treatment of proliferating cells (<10,000 cells/cm(2)) with 0.25 μg/cm(2) (1.25 μg/mL) of 23 nm Ag NP for 24 h induced 15% necrotic cell death and an 80% reduction in metabolic activity and decreased the GSH/GSSG ratio, indicating oxidative stress. G2/M phase cell cycle arrest and complete inhibition of cell proliferation was also induced by Ag NP treatment. Simulated in vitro digestion of Ag NP prior to cell exposure required the use of slightly higher doses to induce the same toxicity, likely due to slower Ag dissolution. Treatment of cells with silica, titania, and ZnO NP partially inhibited cell proliferation, but inhibition at low doses was unique to Ag NP. These data suggest that Ag NP induces oxidative stress, cell cycle arrest, and the inhibition of cell proliferation. However, toxicity and induction of oxidative stress were not observed in confluent cells (>100,000 cells/cm(2)) treated with 10 μg/cm(2) (40-50 μg/mL) Ag NP, indicating that these cells are less sensitive to Ag NP. PMID:26196530

  20. Introduction of Methyl Groups at C2 and C6 Positions Enhances the Antiangiogenesis Activity of Curcumin.

    PubMed

    Koo, Hyun-Jung; Shin, Sarah; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae; Choe, Yearn Seong

    2015-01-01

    Curcumin has diverse biological activities, but is known to undergo rapid metabolism via reduction of vinylic double bonds and phase II conjugation. To prevent reductive metabolism of curcumin, we introduced a methyl group at both C2 and C6 positions (compound 1) or at the C2 position (compound 2) of curcumin, creating steric hindrance on double bonds against metabolizing enzymes. As predicted, these compounds were resistant to reduction by alcohol dehydrogenase. Compound 1 was further evaluated for its antiangiogenesis activity in vitro and in vivo. It exhibited significantly greater inhibitory activity than curcumin against endothelial cell migration, invasion, and tube formation. Similarly, the in vivo Matrigel plug assay in C57BL/6 mice showed more pronounced reduction of blood vessels in the plugs containing 1 than those containing curcumin. Moreover, 1 suppressed tumor growth more effectively than curcumin in a U87MG mouse xenograft model by inhibiting angiogenesis. In vivo metabolite analysis by liquid chromatography/mass spectrometry demonstrated that 1 underwent markedly slower reductive metabolism than curcumin. Taken together, our results indicate that 1 has enhanced antiangiogenesis activity and suppression of tumor growth compared with curcumin, reflecting diminished reductive metabolism owing to the introduction of methyl groups at the C2 and C6 positions of curcumin. PMID:26391485

  1. Introduction of Methyl Groups at C2 and C6 Positions Enhances the Antiangiogenesis Activity of Curcumin

    PubMed Central

    Koo, Hyun-Jung; Shin, Sarah; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae; Choe, Yearn Seong

    2015-01-01

    Curcumin has diverse biological activities, but is known to undergo rapid metabolism via reduction of vinylic double bonds and phase II conjugation. To prevent reductive metabolism of curcumin, we introduced a methyl group at both C2 and C6 positions (compound 1) or at the C2 position (compound 2) of curcumin, creating steric hindrance on double bonds against metabolizing enzymes. As predicted, these compounds were resistant to reduction by alcohol dehydrogenase. Compound 1 was further evaluated for its antiangiogenesis activity in vitro and in vivo. It exhibited significantly greater inhibitory activity than curcumin against endothelial cell migration, invasion, and tube formation. Similarly, the in vivo Matrigel plug assay in C57BL/6 mice showed more pronounced reduction of blood vessels in the plugs containing 1 than those containing curcumin. Moreover, 1 suppressed tumor growth more effectively than curcumin in a U87MG mouse xenograft model by inhibiting angiogenesis. In vivo metabolite analysis by liquid chromatography/mass spectrometry demonstrated that 1 underwent markedly slower reductive metabolism than curcumin. Taken together, our results indicate that 1 has enhanced antiangiogenesis activity and suppression of tumor growth compared with curcumin, reflecting diminished reductive metabolism owing to the introduction of methyl groups at the C2 and C6 positions of curcumin. PMID:26391485

  2. Improved microbial growth inhibition activity of bio-surfactant induced Ag-TiO2 core shell nanoparticles

    NASA Astrophysics Data System (ADS)

    Nithyadevi, D.; Kumar, P. Suresh; Mangalaraj, D.; Ponpandian, N.; Viswanathan, C.; Meena, P.

    2015-02-01

    Surfactant induced silver-titanium dioxide core shell nanoparticles within the size range of 10-50 nm were applied in the antibacterial agent to inhibit the growth of bacterial cells. The single crystalline silver was located in the core part of the composite powder and the titanium dioxide components were uniformly distributed in the shell part. HRTEM and XRD results indicated that silver was completely covered by titanium dioxide and its crystal structure was not affected after being coated by titanium dioxide. The effect of silver-titanium dioxide nanoparticles in the inhibition of bacterial cell growth was studied by means of disk diffusion method. The inhibition zone results reveal that sodium alginate induced silver-titanium dioxide nanoparticles exhibit 100% more antibacterial activity than that with cetyltrimethylbromide or without surfactant. UV-vis spectroscopic analysis showed a large concentration of silver was rapidly released into phosphate buffer solution (PBS) within a period of 1 day, with a much smaller concentration being released after this 1-day period. It was concluded that sodium alginate induced silver-titanium dioxide core shell nanoparticles could enhance long term cell growth inhibition in comparison with cetyltrimethylbromide or without surfactant. The surfactant mediated core shell nanoparticles have comparatively rapid, less expensive and wider applications in modern antibacterial therapy.

  3. Unprecedented inhibition of tubulin polymerization directed by gold nanoparticles inducing cell cycle arrest and apoptosis

    NASA Astrophysics Data System (ADS)

    Choudhury, Diptiman; Xavier, Paulrajpillai Lourdu; Chaudhari, Kamalesh; John, Robin; Dasgupta, Anjan Kumar; Pradeep, Thalappil; Chakrabarti, Gopal

    2013-05-01

    The effect of gold nanoparticles (AuNPs) on the polymerization of tubulin has not been examined till now. We report that interaction of weakly protected AuNPs with microtubules (MTs) could cause inhibition of polymerization and aggregation in the cell free system. We estimate that single citrate capped AuNPs could cause aggregation of ~105 tubulin heterodimers. Investigation of the nature of inhibition of polymerization and aggregation by Raman and Fourier transform-infrared (FTIR) spectroscopies indicated partial conformational changes of tubulin and microtubules, thus revealing that AuNP-induced conformational change is the driving force behind the observed phenomenon. Cell culture experiments were carried out to check whether this can happen inside a cell. Dark field microscopy (DFM) combined with hyperspectral imaging (HSI) along with flow cytometric (FC) and confocal laser scanning microscopic (CLSM) analyses suggested that AuNPs entered the cell, caused aggregation of the MTs of A549 cells, leading to cell cycle arrest at the G0/G1 phase and concomitant apoptosis. Further, Western blot analysis indicated the upregulation of mitochondrial apoptosis proteins such as Bax and p53, down regulation of Bcl-2 and cleavage of poly(ADP-ribose) polymerase (PARP) confirming mitochondrial apoptosis. Western blot run after cold-depolymerization revealed an increase in the aggregated insoluble intracellular tubulin while the control and actin did not aggregate, suggesting microtubule damage induced cell cycle arrest and apoptosis. The observed polymerization inhibition and cytotoxic effects were dependent on the size and concentration of the AuNPs used and also on the incubation time. As microtubules are important cellular structures and target for anti-cancer drugs, this first observation of nanoparticles-induced protein's conformational change-based aggregation of the tubulin-MT system is of high importance, and would be useful in the understanding of cancer therapeutics

  4. Curcumin and Emodin Down-Regulate TGF-β Signaling Pathway in Human Cervical Cancer Cells

    PubMed Central

    Thacker, Pooja Chandrakant; Karunagaran, Devarajan

    2015-01-01

    Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer. PMID:25786122

  5. Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis

    PubMed Central

    Wang, Ying; Wu, Wenjuan; Polin, Lisa; Sharma, Sunita; Levi, Edi; Albelda, Steven; Pass, Harvey I.; Wali, Anil

    2013-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has been under investigation for a number of cancers. In this study, we investigated the biological and molecular responses of MPM cells to curcumin treatments and the mechanisms involved. Flow-cytometric analyses coupled with western immunoblotting and gene-array analyses were conducted to determine mechanisms of curcumin-dependent growth suppression of human (H2373, H2452, H2461, and H226) and murine (AB12) MPM cells. Curcumin inhibited MPM cell growth in a dose- and time-dependent manner while pretreatment of MPM cells with curcumin enhanced cisplatin efficacy. Curcumin activated the stress-activated p38 kinase, caspases 9 and 3, caused elevated levels of proapoptotic proteins Bax, stimulated PARP cleavage, and apoptosis. In addition, curcumin treatments stimulated expression of novel transducers of cell growth suppression such as CARP-1, XAF1, and SULF1 proteins. Oral administration of curcumin inhibited growth of murine MPM cell-derived tumors in vivo in part by stimulating apoptosis. Thus, curcumin targets cell cycle and promotes apoptosis to suppress MPM growth in vitro and in vivo. Our studies provide a proof-of-principle rationale for further in-depth analysis of MPM growth suppression mechanisms and their future exploitation in effective management of resistant MPM. PMID:21594647

  6. Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis.

    PubMed

    Wang, Ying; Rishi, Arun K; Wu, Wenjuan; Polin, Lisa; Sharma, Sunita; Levi, Edi; Albelda, Steven; Pass, Harvey I; Wali, Anil

    2011-11-01

    Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has been under investigation for a number of cancers. In this study, we investigated the biological and molecular responses of MPM cells to curcumin treatments and the mechanisms involved. Flow-cytometric analyses coupled with western immunoblotting and gene-array analyses were conducted to determine mechanisms of curcumin-dependent growth suppression of human (H2373, H2452, H2461, and H226) and murine (AB12) MPM cells. Curcumin inhibited MPM cell growth in a dose- and time-dependent manner while pretreatment of MPM cells with curcumin enhanced cisplatin efficacy. Curcumin activated the stress-activated p38 kinase, caspases 9 and 3, caused elevated levels of proapoptotic proteins Bax, stimulated PARP cleavage, and apoptosis. In addition, curcumin treatments stimulated expression of novel transducers of cell growth suppression such as CARP-1, XAF1, and SULF1 proteins. Oral administration of curcumin inhibited growth of murine MPM cell-derived tumors in vivo in part by stimulating apoptosis. Thus, curcumin targets cell cycle and promotes apoptosis to suppress MPM growth in vitro and in vivo. Our studies provide a proof-of-principle rationale for further in-depth analysis of MPM growth suppression mechanisms and their future exploitation in effective management of resistant MPM. PMID:21594647

  7. Effect of curcumin on human colon cancer multidrug resistance in vitro and in vivo

    PubMed Central

    Lu, Wei-Dong; Qin, Yong; Yang, Chuang; Li, Lei

    2013-01-01

    OBJECTIVE: To determine whether curcumin reverses the multidrug resistance of human colon cancer cells in vitro and in vivo. METHODS: In a vincristine-resistant cell line of human colon cancer, the cell viability of curcumin-treated cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Rhodamine123 efflux was evaluated to detect P-glycoprotein transporter activity, and expression of the multidrug resistance protein 1 and survivin genes was analyzed by reverse transcription polymerase chain reaction and western blotting. In addition, xenograft mouse tumors were grown and treated with curcumin. The morphology of the xenografts was investigated by hematoxylin-eosin staining. The in vivo expression of the multidrug resistance gene and P-glycoprotein and survivin genes and proteins was observed using reverse transcription-polymerase chain reaction and western blotting, respectively. RESULTS: Curcumin was not obviously toxic to the vincristine-resistant human colon cancer cells at concentrations less than 25 μM, but the growth of cells was significantly inhibited. At concentrations greater than 25 μM, curcumin was toxic in a concentration-dependent manner. The sensitivity of cells to vincristine, cisplatin, fluorouracil, and hydroxycamptothecin was enhanced, intracellular Rhodamine123 accumulation was increased (p<0.05), and the expression of the multidrug resistance gene and P-glycoprotein were significantly suppressed (p<0.05). The combination of curcumin and vincristine significantly inhibited xenograft growth. The expression of the multidrug resistance protein 1 and survivin genes was significantly reduced in xenografts of curcumin-treated mice and mice treated with both curcumin and vincristine relative to control mice. CONCLUSION: Curcumin has strong reversal effects on the multidrug resistance of human colon carcinoma in vitro and in vivo. PMID:23778405

  8. Nanoparticle-facilitated autophagy inhibition promotes the efficacy of chemotherapeutics against breast cancer stem cells.

    PubMed

    Sun, Rong; Shen, Song; Zhang, Yun-Jiao; Xu, Cong-Fei; Cao, Zhi-Ting; Wen, Long-Ping; Wang, Jun

    2016-10-01

    Cancer stem cells (CSCs) have garnered increasing attention over the past decade, as they are believed to play a crucial role in tumor initiation, progression and metastasis, relapse and drug resistance. Therapeutic strategies which simultaneously exterminate both bulk tumor cells and the rare CSC subpopulation may produce striking response and result in long-term tumor remission. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival of CSCs. The role of autophagy in the susceptibility of breast CSCs to chemotherapeutics was investigated in the present work, reduced 'stemness' and increased susceptibility to chemotherapy drugs (doxorubicin, DOX and docetaxel, DTXL) were observed after chloroquine (CQ)-mediated autophagy inhibition in sorted ALDH(hi) cells of breast cancer cell line MDA-MB-231. We further proved that nanoparticle-mediated autophagy inhibition promoted the efficacy of chemotherapeutics against ALDH(hi) MDA-MB-231 cells in vitro. Administration of drug delivery systems significantly prolonged the circulation half-life and augmented enrichment of two different drugs in tumor tissues and ALDH(hi) cells. More importantly, compared with single treatment, the combined delivery systems NPCQ/NPDOX and NPCQ/DOX (NPCQ/NPDTXL and NPCQ/DTXL) showed most effective and persistent tumor growth inhibitory effect by eliminating bulk tumor cells as well as CSCs (p < 0.01) in an MDA-MB-231 orthotopic tumor murine model. Therefore, our research provides new insights into the nanoparticle-facilitated combination of autophagy inhibition and chemotherapy for effective therapy of breast cancer. PMID:27376558

  9. Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

    PubMed Central

    Xie, Ping; Zhang, WeiWei; Yuan, Songtao; Chen, Zhiqiang; Yang, Qin; Yuan, DongQing; Wang, Feng; Liu, QingHuai

    2012-01-01

    Purpose To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. Methods C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)−1α in the RPE-choroid was determined by Western blotting. Results Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF−1α (P<0.05). Conclusion Curcumin treatment led to the suppression of CNV development

  10. Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro

    PubMed Central

    Xiao, Jie; Sheng, Xi; Zhang, Xinyu; Guo, Mengqi; Ji, Xiaoping

    2016-01-01

    Curcumin, a polyphenolic compound derived from turmeric, protects against myocardial injury by alleviating oxidative stress, inflammation, apoptosis, and fibrosis. However, the role of curcumin and its mechanism of action on interstitial fibrosis after myocardial infarction (MI) are poorly understood. To clarify, MI was induced by a permanent ligation of the left anterior descending coronary artery in adult mice, and the effects of curcumin were evaluated 4 weeks after the MI event. In vitro, we treated cardiac fibroblasts (CFs) with Ang II, and investigated the anti-fibrotic mechanism of curcumin. Our results showed that curcumin significantly attenuated collagen deposition in vivo and inhibited CF proliferation and migration, and MMP expression. In addition, we found that the down-regulation of SIRT1 after MI was attenuated by curcumin pretreatment, which indicated that the activation of SIRT1 might be involved in the protective action of curcumin. This hypothesis was confirmed by genetic inhibition of SIRT1 (siRNA-SIRT1) in Ang II-treated CFs. Our results provide new insights into the mechanism underlying the anti-fibrotic effects of curcumin in the heart. PMID:27099472

  11. Synthesis and characterization of fluorinated magnetic core-shell nanoparticles for inhibition of insulin amyloid fibril formation

    NASA Astrophysics Data System (ADS)

    Skaat, Hadas; Belfort, Georges; Margel, Shlomo

    2009-06-01

    Maghemite (γ-Fe2O3) magnetic nanoparticles of 15.0 ± 2.1 nm are formed by nucleation followed by controlled growth of maghemite thin films on gelatin-iron oxide nuclei. Uniform magnetic γ-Fe2O3/poly (2,2,3,3,4,4,4-heptafluorobutyl acrylate) (γ-Fe2O3/PHFBA) core-shell nanoparticles are prepared by emulsion polymerization of the fluorinated monomer 2,2,3,3,4,4,4-heptafluorobutyl acrylate (HFBA) in the presence of the maghemite nanoparticles. The kinetics of the insulin fibrillation process in the absence and in the presence of the γ-Fe2O3/PHFBA core-shell nanoparticles are elucidated. A significant direct slow transition from α-helix to β-sheets during insulin fibril formation is observed in the presence of the γ-Fe2O3/PHFBA nanoparticles. This is in contradiction to our previous manuscript, which illustrated that the γ-Fe2O3 core nanoparticles do not affect the kinetics of the formation of the insulin fibrils, and to other previous publications that describe acceleration of the fibrillation process by using various types of nanoparticles. These core-shell nanoparticles may therefore be also useful for the inhibition of conformational changes of other amyloidogenic proteins that lead to neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, mad cow and prion diseases.

  12. PPARgamma agonist curcumin reduces the amyloid-beta-stimulated inflammatory responses in primary astrocytes.

    PubMed

    Wang, Hong-Mei; Zhao, Yan-Xin; Zhang, Shi; Liu, Gui-Dong; Kang, Wen-Yan; Tang, Hui-Dong; Ding, Jian-Qing; Chen, Sheng-Di

    2010-01-01

    Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Accumulating data indicate that astrocytes play an important role in the neuroinflammation related to the pathogenesis of AD. It has been shown that microglia and astrocytes are activated in AD brain and amyloid-beta (Abeta) can increase the expression of cyclooxygenase 2 (COX-2), interleukin-1, and interleukin-6. Suppressing the inflammatory response caused by activated astrocytes may help to inhibit the development of AD. Curcumin is a major constituent of the yellow curry spice turmeric and proved to be a potential anti-inflammatory drug in arthritis and colitis. There is a low age-adjusted prevalence of AD in India, a country where turmeric powder is commonly used as a culinary compound. Curcumin has been shown to suppress activated astroglia in amyloid-beta protein precursor transgenic mice. The real mechanism by which curcumin inhibits activated astroglia is poorly understood. Here we report that the expression of COX-2 and glial fibrillary acidic protein were enhanced and that of peroxisome proliferator-activated receptor gamma (PPARgamma) was decreased in Abeta(25-35)-treated astrocytes. In line with these results, nuclear factor-kappaB translocation was increased in the presence of Abeta. All these can be reversed by the pretreatment of curcumin. Furthermore, GW9662, a PPARgamma antagonist, can abolish the anti-inflammatory effect of curcumin. These results show that curcumin might act as a PPARgamma agonist to inhibit the inflammation in Abeta-treated astrocytes. PMID:20413894

  13. Shape-Dependent Biomimetic Inhibition of Enzyme by Nanoparticles and Their Antibacterial Activity.

    PubMed

    Cha, Sang-Ho; Hong, Jin; McGuffie, Matt; Yeom, Bongjun; VanEpps, J Scott; Kotov, Nicholas A

    2015-09-22

    Enzyme inhibitors are ubiquitous in all living systems, and their biological inhibitory activity is strongly dependent on their molecular shape. Here, we show that small zinc oxide nanoparticles (ZnO NPs)-pyramids, plates, and spheres-possess the ability to inhibit activity of a typical enzyme β-galactosidase (GAL) in a biomimetic fashion. Enzyme inhibition by ZnO NPs is reversible and follows classical Michaelis-Menten kinetics with parameters strongly dependent on their geometry. Diverse spectroscopic, biochemical, and computational experimental data indicate that association of GAL with specific ZnO NP geometries interferes with conformational reorganization of the enzyme necessary for its catalytic activity. The strongest inhibition was observed for ZnO nanopyramids and compares favorably to that of the best natural GAL inhibitors while being resistant to proteases. Besides the fundamental significance of this biomimetic function of anisotropic NPs, their capacity to serve as degradation-resistant enzyme inhibitors is technologically attractive and is substantiated by strong shape-specific antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), endemic for most hospitals in the world. PMID:26325486

  14. The inhibition of advanced glycation end-products-induced retinal vascular permeability by silver nanoparticles.

    PubMed

    Sheikpranbabu, Sardarpasha; Kalishwaralal, Kalimuthu; Lee, Kyung-Jin; Vaidyanathan, Ramanathan; Eom, Soo Hyun; Gurunathan, Sangiliyandi

    2010-03-01

    The increased permeability of the blood-retinal barrier is known to occur in patients with diabetes, and this defect contributes to retinal edema. This study aimed to determine the effects of silver nanoparticles (Ag-NPs) on advanced glycation end-products (AGEs)-induced endothelial cell permeability. Cultured porcine retinal endothelial cells (PRECs) were exposed to AGE-modified bovine serum albumin (AGE-BSA) and the endothelial cell permeability was detected by measuring the flux of RITC-dextran across the PREC monolayers. We found that AGE-BSA increased the dextran flux across a PREC monolayer and Ag-NPs blocked the solute flux induced by AGE-BSA. In order to understand the underlying signaling mechanism of Ag-NPs on the inhibitory effect of AGE-BSA-induced permeability, we demonstrated that Ag-NPs could inhibit the AGE-BSA-induced permeability via Src kinase pathway. AGE-BSA also increased the PREC permeability by stimulating the expression of intracellular adhesion molecule-1 (ICAM-1) and decreased the expression of occludin and ZO-1. Further, Ag-NPs inhibited the AGE-BSA-induced permeability by increased expression of tight junction proteins occludin and ZO-1, co-incident with an increase in barrier properties of endothelial monolayer. Together, our results indicate that Ag-NPs could possibly act as potent anti-permeability molecule by targeting the Src signaling pathway and tight junction proteins and it offers potential targets to inhibit the ocular related diseases. PMID:19963272

  15. Improvement of bioavailability and anti-inflammatory potential of curcumin in combination with emu oil.

    PubMed

    Jeengar, Manish Kumar; Shrivastava, Shweta; Nair, Kala; Singareddy, Sreenivasa Reddy; Putcha, Uday Kumar; Talluri, M V N Kumar; Naidu, V G M; Sistla, Ramakrishna

    2014-12-01

    The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund's complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis. PMID:25028100

  16. Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells*

    PubMed Central

    Wang, Jin-bo; Qi, Li-li; Zheng, Shui-di; Wu, Tian-xing

    2009-01-01

    Objective: To investigate the effects of curcumin on release of cytochrome c and expressions of Bcl-2, Bax, Bad, Bcl-xL, caspase-3, poly ADP-ribose polymerase (PARP), and survivin of HT-29 cells. Methods: HT-29 cells were treated with curcumin (0~80 μmol/L) for 24 h. The release of cytochrome c from the mitochondria and the apoptosis-related proteins Bax, Bcl-2, Bcl-xL, Bad, caspase-3, PARP, and survivin were determined by Western blot analysis and their mRNA expressions by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Curcumin significantly induced the growth inhibition and apoptosis of HT-29 cells. A decrease in expressions of Bcl-2, Bcl-xL and survivin was observed after exposure to 10~80 μmol/L curcumin, while the levels of Bax and Bad increased in the curcumin-treated cells. Curcumin also induced the release of cytochrome c, the activation of caspase-3, and the cleavage of PARP in a dose-dependent manner. Conclusion: These data suggest that curcumin induced the HT-29 cell apoptosis possibly via the mitochondria-mediated pathway. PMID:19235267

  17. Curcumin Rescues Diabetic Renal Fibrosis by Targeting Superoxide-Mediated Wnt Signaling Pathways.

    PubMed

    Ho, Cheng; Hsu, Yung-Chien; Lei, Chen-Chou; Mau, Shu-Ching; Shih, Ya-Hsueh; Lin, Chun-Liang

    2016-03-01

    The purposes of this study were to investigate whether curcumin can weaken diabetic nephropathy by modulating both oxidative stress and renal injury from Wnt signaling mediation. Wnt5a/β-catenin depression and induction of superoxide synthesis are associated with high glucose (HG) induced transforming growth factor (TGF)-β1 and fibronectin expression in mesangial cells. Curcumin resumes HG depression of Wnt/β-catenin signaling and alleviates HG induction of superoxide, TGF-β1 and fibronectin expression in renal mesangial cell. Exogenous curcumin alleviated urinary total proteinuria and serum superoxide level in diabetic rats. Based on laser-captured microdissection for quantitative real-time polymerase chain reaction, it was found that diabetes significantly increased TGF-β1 and fibronectin expression in line with depressed Wnt5a expression. Curcumin treatment reduced the TGF-β1 and fibronectin activation and the inhibiting effect of diabetes on Wnt5a/β-catenin expression in renal glomeruli. Immunohistochemistry showed that curcumin treatment significantly reduced 8-hydroxy-2'-deoxyguanosine, TGF-β1 and fibronectin, and was in line with the restoration of the suppressed Wnt5a expression immunoreactivities in glomeruli of diabetic rats. Curcumin alleviated extracellular matrix accumulation in diabetic nephropathy by not only preventing the diabetes-mediated superoxide synthesis but also resuming downregulation of Wnt/β-catenin signaling. These findings suggest that regulation of Wnt activity by curcumin is a feasible alternative strategy to rescue diabetic renal injury. PMID:26992258

  18. Curcumin for the prevention of progression in monoclonal gammopathy of undetermined significance: A word of caution.

    PubMed

    Vermorken, A J M; Zhu, J; VAN DE Ven, W J M; Cui, Y; Fryns, J P

    2010-03-01

    A recent pilot study found that curcumin, in certain patients with monoclonal gammopathy of undetermined significance (MGUS), decreases the paraprotein load and the urinary N-telopeptide of type 1 collagen bone turnover marker. While this result is encouraging, the easy availability of the food component turmeric, containing curcumin, may lead to intake by MGUS patients without medical supervision. Curcumin is generally considered safe. Nevertheless, it is known that curcumin inhibits interleukin-12 production in dendritic cells, thereby dampening the Th1 response. It is also well established that Th1 cells are protective against invading pathogens and tumors. The present study describes a case in which bronchitis developed upon turmeric intake for gastrointestinal complaints. While one case does not provide proof of curcumin toxicity, a thorough literature overview suggests that turmeric may have an immunosuppressive effect, notably in patients with a compromised immune system. A warning against the use of turmeric or curcumin without medical supervision in immunocompromised patients seems therefore very opportune. Patients with MGUS, in whom the levels of non-affected immunoglobulins are reduced, should be carefully monitored for toxicity when curcumin is administered. PMID:22993538

  19. The application of Fe3O4 nanoparticles in cancer research: a new strategy to inhibit drug resistance.

    PubMed

    Wang, Xuemei; Zhang, Renyun; Wu, Chunhui; Dai, Yongyuan; Song, Min; Gutmann, Sebastian; Gao, Feng; Lv, Gang; Li, Jingyuan; Li, Xiaomao; Guan, Zhiqun; Fu, Degang; Chen, Baoan

    2007-03-15

    Although much effort has been extended to the efficient cancer therapies, the drug resistance is still a major obstacle in cancer chemotherapeutic treatments. Almost 90% of the cancer therapy failure is caused by the relative problems. Recently, the application of drug coated polymer nanospheres and nanoparticles to inhibit the related drug resistance has attracted much attention. In this report, we have explored a novel strategy to inhibit the multidrug resistance of the targeted tumor cells by combining the unique properties of tetraheptylammonium capped Fe(3)O(4) magnetic nanoparticles with the drug accumulation of anticancer drug daunorubicin. Our results of confocal fluorescence and atomic force microscopy (AFM) as well as electrochemical studies demonstrate the remarkable synergistic effect of Fe(3)O(4) nanoparticles on drug uptake of daunorubicin in leukemia K562 cells. These observations indicate that the interaction between the magnetic nanoparticles Fe(3)O(4) and biologically active molecules on the membrane of leukemia cell lines may contribute to their beneficial effect on cellular uptake so that the synergistic enhanced effect of magnetic nanoparticles Fe(3)O(4) on drug uptake of drug resistance leukemia K562 cells could be observed upon application of the Fe(3)O(4) nanoparticles. PMID:17072850

  20. Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver.

    PubMed

    Oetari, S; Sudibyo, M; Commandeur, J N; Samhoedi, R; Vermeulen, N P

    1996-01-12

    The stability of curcumin, as well as the interactions between curcumin and cytochrome P450s (P450s) and glutathione S-transferases (GSTs) in rat liver, were studied. Curcumin is relatively unstable in phosphate buffer at pH 7.4. The stability of curcumin was strongly improved by lowering the pH or by adding glutathione (GSH), N-acetyl L-cysteine (NAC), ascorbic acid, rat liver microsomes, or rat liver cytosol. Curcumin was found to be a potent inhibitor of rat liver P450 1A1/1A2 measured as ethoxyresorufin deethylation (EROD) activity in beta-naphthoflavone (beta NF)-induced microsomes, a less potent inhibitor of P450 2B1/2B2, measured as pentoxyresorufin depentylation (PROD) activity in phenobarbital (PB)-induced microsomes and a weak inhibitor of P450 2E1, measured as p-nitrophenol (PNP) hydroxylation activity in pyrazole-induced microsomes. Ki values were 0.14 and 76.02 microM for the EROD- and PROD-activities, respectively, and 30 microM of curcumin inhibited only 9% of PNP-hydroxylation activity. In ethoxyresorufin deethylation (EROD) and pentoxyresorufin depentylation (PROD) experiments, curcumin showed a competitive type of inhibition. Curcumin was also a potent inhibitor of glutathione S-transferase (GST) activity in cytosol from liver of rats treated with phenobarbital (PB), beta-naphthoflavone (beta NF) and pyrazole (Pyr), when measured towards 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. In liver cytosol from rats treated with phenobarbital (PB), curcumin inhibited GST activity in a mixed-type manner with a Ki of 5.75 microM and Ki of 12.5 microM. In liver cytosol from rats treated with pyrazole (Pyr) or beta-naphthoflavone (beta NF), curcumin demonstrated a competitive type of inhibition with Ki values of 1.79 microM and 2.29 microM, respectively. It is concluded that these strong inhibitory properties of curcumin towards P450s and GSTs, in addition to its well-known antioxidant activity, may help explain the previously observed anticarcinogenic

  1. Cuprous oxide nanoparticles inhibit the growth and metastasis of melanoma by targeting mitochondria

    PubMed Central

    Wang, Y; Yang, F; Zhang, H-X; Zi, X-Y; Pan, X-H; Chen, F; Luo, W-D; Li, J-X; Zhu, H-Y; Hu, Y-P

    2013-01-01

    Metal and its oxide nanoparticles show ideal pharmacological activity, especially in anti-tumor therapy. Our previous study demonstrated that cuprous oxide nanoparticles (CONPs) selectively induce apoptosis of tumor cells in vitro. To explore the anti-tumor properties of CONPs in vivo, we used the particles to treat mouse subcutaneous melanoma and metastatic lung tumors, based on B16-F10 mouse melanoma cells, by intratumoral and systemic injections, respectively. The results showed that CONPs significantly reduced the growth of melanoma, inhibited the metastasis of B16-F10 cells and increased the survival rate of tumor-bearing mice. Importantly, the results also indicated that CONPs were rapidly cleared from the organs and that these particles exhibited little systemic toxicity. Furthermore, we observed that CONPs targeted the mitochondria, which resulted in the release of cytochrome C from the mitochondria and the activation of caspase-3 and caspase-9 after the CONPs entered the cells. In conclusion, CONPs can induce the apoptosis of cancer cells through a mitochondrion-mediated apoptosis pathway, which raises the possibility that CONPs could be used to cure melanoma and other cancers. PMID:23990023

  2. Dual effects of β-cyclodextrin-stabilised silver nanoparticles: enhanced biofilm inhibition and reduced cytotoxicity.

    PubMed

    Jaiswal, Swarna; Bhattacharya, Kunal; McHale, Patrick; Duffy, Brendan

    2015-01-01

    The composition and mode of synthesis of nanoparticles (NPs) can affect interaction with bacterial and human cells differently. The present work describes the ability of β-cyclodextrin (β-CD) capped silver nanoparticles (AgNPs) to inhibit biofilm growth and reduce cytotoxicity. Biofilm formation of Staphylococcus epidermidis CSF 41498 was quantified by a crystal violet assay in the presence of native and capped AgNPs (Ag-10CD and Ag-20CD), and the morphology of the biofilm was observed by scanning electron microscope. The cytotoxicity of the AgNPs against HaCat cells was determined by measuring the increase in intracellular reactive oxygen species and change in mitochondrial membrane potential (ΔΨm). Results indicated that capping AgNPs with β-CD improved their efficacy against S. epidermidis CSF 41498, reduced biofilm formation and their cytotoxicity. The study concluded that β-CD is an effective capping and stabilising agent that reduces toxicity of AgNPs against the mammalian cell while enhancing their antibiofilm activity. PMID:25596861

  3. Suppression of protein kinase C and nuclear oncogene expression as possible action mechanisms of cancer chemoprevention by Curcumin.

    PubMed

    Lin, Jen-Kun

    2004-07-01

    Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C (PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and IkappaB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)kappaB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction pathways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins play a pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans. PMID:15356994

  4. Effects of curcumin on cancer cell mitochondrial function and potential monitoring with ¹⁸F-FDG uptake.

    PubMed

    Jung, Kyung-Ho; Lee, Jin Hee; Park, Jin Won; Moon, Seung-Hwan; Cho, Young Seok; Choe, Yearn Seong; Lee, Kyung-Han

    2016-02-01

    A better understanding of how curcumin influences cancer cell biology could help devise new strategies to enhance its antitumor effect. Many curcumin actions are proposed to occur by targeting mitochondrial function, among which glucose metabolism and reactive oxygen species (ROS) production are pivotal. However, little is known of how curcumin influences cancer cell glucose metabolism. We thus evaluated the effect of curcumin on cancer cell glucose metabolism and mitochondrial function, and further investigated whether these responses could be modified to enhance the anticancer potency of the compound. MCF-7 breast cancer cells treated with curcumin were measured for 18F-fluorodeoxyglucose (18F‑FDG) uptake, lactate production, hexokinase activity, oxygen consumption rate (OCR), ROS production and mitochondrial membrane potential (MMP). Activation of signaling pathways was evaluated by western blots, and cell survival was assessed with sulforhodamine B assays. Curcumin stimulated a 3.6-fold increase of 18F-FDG uptake in MCF-7 cells, along with augmented hexokinase activity and lactate efflux. This was accompanied by significantly suppressed cellular OCR, consistent with a metabolic shift to glycolytic flux. Inhibiting this metabolic response with 2-deoxyglucose (2-DG) blocked curcumin-induced mTOR activation and resulted in a greater anti-proliferative effect. Curcumin-induced MMP depolarization led to reduced ROS production, which may hinder the anticancer effect of the compound. Intracellular ROS was completely restored by adding Cu2+, which can bind and modify the curcumin's physico-chemical property, and this resulted in a marked potentiation of its anti-proliferative effect. Thus, curcumin suppresses cancer cell MMP and ROS generation, and this response is accompanied by stimulated 18F-FDG uptake via shifting of metabolism from mitochondrial respiration to glycolytic flux. These mitochondrial and metabolic responses may provide potential targets that can

  5. Enhanced antitumor effect of curcumin liposomes with local hyperthermia in the LL/2 model.

    PubMed

    Tang, Jian-Cai; Shi, Hua-Shan; Wan, Li-Qiang; Wang, Yong-Sheng; Wei, Yu-Quan

    2013-01-01

    Curcumin previously was proven to inhibit angiogenesis and display potent antitumor activity in vivo and in vitro. In the present study, we investigated whether a combination curcumin with hyperthermia would have a synergistic antitumor effect in the LL/2 model. The results indicated that combination therapy significantly inhibited cell proliferation of MS-1 and LL/2 in vitro. LL/2 experiment model also demonstrated that the combination therapy inhibited tumor growth and prolonged the life span in vivo. Furthermore, combination therapy reduced angiogenesis and increased tumor apoptosis. Our findings suggest that the combination therapy exerted synergistic antitumor effects, providing a new perspective fpr clinical tumor therapy. PMID:23725132

  6. Curcumin induced human gastric cancer BGC-823 cells apoptosis by ROS-mediated ASK1-MKK4-JNK stress signaling pathway.

    PubMed

    Liang, Tao; Zhang, Xiaojian; Xue, Wenhua; Zhao, Songfeng; Zhang, Xiang; Pei, Jianying

    2014-01-01

    The signaling mediated by stress-activated MAP kinases (MAPK), c-Jun N-terminal kinase (JNK) has well-established importance in cancer. In the present report, we investigated the effects of curcumin on the signaling pathway in human gastric cancer BGC-823 cells. Curcumin induced reactive oxygen species (ROS) production and BGC-823 cells apoptosis. Inhibition of ROS generation by antioxidant (NAC or Trion) significantly prevented curcumin-mediated apoptosis. Notably, we observed that curcumin activated ASK1, a MAPKKK that is oxidative stress sensitive and responsible to phosphorylation of JNK via triggering cascades, up-regulated an upstream effector of the JNK, MKK4, and phosphorylated JNK protein expression in BGC-823 cells. However, curcumin induced ASK1-MKK4-JNK signaling was attenuated by NAC. All the findings confirm the possibility that oxidative stress-activated ASK1-MKK4-JNK signaling cascade promotes the apoptotic response in curcumin-treated BGC-823 cells. PMID:25198898

  7. Curcumin Induced Human Gastric Cancer BGC-823 Cells Apoptosis by ROS-Mediated ASK1-MKK4-JNK Stress Signaling Pathway

    PubMed Central

    Liang, Tao; Zhang, Xiaojian; Xue, Wenhua; Zhao, Songfeng; Zhang, Xiang; Pei, Jianying

    2014-01-01

    The signaling mediated by stress-activated MAP kinases (MAPK), c-Jun N-terminal kinase (JNK) has well-established importance in cancer. In the present report, we investigated the effects of curcumin on the signaling pathway in human gastric cancer BGC-823 cells. Curcumin induced reactive oxygen species (ROS) production and BGC-823 cells apoptosis. Inhibition of ROS generation by antioxidant (NAC or Trion) significantly prevented curcumin-mediated apoptosis. Notably, we observed that curcumin activated ASK1, a MAPKKK that is oxidative stress sensitive and responsible to phosphorylation of JNK via triggering cascades, up-regulated an upstream effector of the JNK, MKK4, and phosphorylated JNK protein expression in BGC-823 cells. However, curcumin induced ASK1-MKK4-JNK signaling was attenuated by NAC. All the findings confirm the possibility that oxidative stress-activated ASK1-MKK4-JNK signaling cascade promotes the apoptotic response in curcumin-treated BGC-823 cells. PMID:25198898

  8. Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

    SciTech Connect

    Dudás, József; Fullár, Alexandra; Romani, Angela; Pritz, Christian; Kovalszky, Ilona; Hans Schartinger, Volker; Mathias Sprinzl, Georg; Riechelmann, Herbert

    2013-04-01

    Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells.

  9. The effect of curcumin on liver fibrosis in the rat model of microsurgical cholestasis.

    PubMed

    Barta, Andrej; Janega, Pavol; Babál, Pavel; Murár, Erich; Cebová, Martina; Pechánová, Olga

    2015-07-01

    We aimed to determine the effects of curcumin on liver fibrosis and to clarify the role of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) in a model of microsurgical cholestasis in the early stage of extrahepatic biliary atresia. Twelve-week-old Wistar rats were divided into four groups (n = 8): sham-operated rats (received olive oil after laparotomy); a curcumin group (received curcumin, 200 mg kg(-1) per day, after laparotomy); a biliary duct ligated group (BDL, received olive oil after operation); and a biliary duct ligated/curcumin group (BDL curc, received curcumin, 200 mg kg(-1) per day, after operation). After 3 weeks of treatment, curcumin did not modify blood plasma markers as well as the expressions of iNOS and NF-κB (p65) in the livers of the sham group. Interestingly, there was a significant increase in the extent of both liver and kidney fibrosis. On the other hand, despite a decrease in the expression of iNOS and NF-κB (p65), treatment with curcumin did not affect fibrosis enlargement due to bile duct ligation in the liver. In the BDL group, treatment with curcumin decreased the level of blood plasma markers investigated. In conclusion, treatment with curcumin was able to improve the functional properties of hepatocytes and to inhibit the upregulations of both NF-κB and iNOS in the BDL group; however, no beneficial effect was observed on the liver fibrosis developed in this model of cholestasis. Thus, in the studied model of microsurgical cholestasis, other factors different from NF-κB and iNOS are responsible for fibrotic processes in the liver. PMID:26039974

  10. Curcumin-encapsulating Nanogels as an Effective Anticancer Formulation for Intracellular Uptake

    PubMed Central

    Reeves, Anna; Vinogradov, Serguei V.; Morrissey, Phil; Chernin, Mitchell; Ahmed, Mansoor M.

    2016-01-01

    Nanoscale drug delivery systems represent an attractive strategy to improve both the efficacy and safety of anticancer drugs. In this work, we describe nanoformulation of curcumin, a most potent natural anticancer compound capable of killing cancer cells while sparing the normal tissues. Since curcumin is a natural hydrophobic polyphenol, it has a low aqueous solubility and bioavailability, which are challenging to its therapeutic efficacy. We dev