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1

Altering Iron Oxide Nanoparticle Surface Properties Induce Cortical Neuron Cytotoxicity  

PubMed Central

Superparamagnetic iron oxide nanoparticles, with diameters in the range of a few tens of nanometers, display the ability to cross the blood-brain barrier and are envisioned as diagnostic and therapeutic tools in neuro-medicine. However, despite the numerous applications being explored, insufficient information is available on their potential toxic effect on neurons. While iron oxide has been shown to pose a decreased risk of toxicity, surface functionalization, often employed for targeted delivery, can significantly alter the biological response. This aspect is addressed in the present study, which investigates the response of primary cortical neurons to iron oxide nanoparticles with coatings frequently used in biomedical applications: aminosilane, dextran, and polydimethylamine. Prior to administering the particles to neuronal cultures, each particle type was thoroughly characterized to assess the (1) size of individual nanoparticles, (2) concentration of the particles in solution and (3) agglomeration size and morphology. Culture results show that polydimethylamine functionalized nanoparticles induce cell death at all concentrations tested by swift and complete removal of the plasma membrane. Aminosilane coated particles affected metabolic activity only at higher concentrations while leaving the membrane intact and dextran-coated nanoparticles partially altered viability at higher concentrations. These findings suggest that nanoparticle characterization and primary cell-based cytotoxicity evaluation should be completed prior to applying nanomaterials to the nervous system. PMID:22111864

Rivet, Christopher J.; Yuan, Yuan; Borca-Tasciuc, Diana-Andra; Gilbert, Ryan J.

2014-01-01

2

Gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441  

Microsoft Academic Search

BACKGROUND: During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles

Chiara Uboldi; Daniele Bonacchi; Giada Lorenzi; M Iris Hermanns; Christine Pohl; Giovanni Baldi; Ronald E Unger; C James Kirkpatrick

2009-01-01

3

Exposure to ZnO nanoparticles induces oxidative stress and cytotoxicity in human colon carcinoma cells  

SciTech Connect

Engineered nanoparticles offer great promise in many industrial and biomedical applications, however little information is available about gastrointestinal toxicity. The purpose of this study was to assess the cytotoxicity, oxidative stress, apoptosis and proinflammatory mediator release induced by ZnO nanoparticles on human colon carcinoma LoVo cells. The biological activity of these particles was related to their physico-chemical characteristics. The physico-chemical characteristics were evaluated by analytical electron microscopy. The cytotoxicity was determined by growth curves and water-soluble tetrazolium assay. The reactive oxygen species production, cellular glutathione content, changes of mitochondrial membrane potential and apoptosis cell death were quantified by flow cytometry. The inflammatory cytokines were evaluated by enzyme-linked immunoadsorbent assay. Treatment with ZnO (5 {mu}g/cm{sup 2} corresponding to 11.5 {mu}g/ml) for 24 h induced on LoVo cells a significant decrease of cell viability, H{sub 2}O{sub 2}/OH{center_dot} increase, O2{sup -{center_dot}} and GSH decrease, depolarization of inner mitochondrial membranes, apoptosis and IL-8 release. Higher doses induced about 98% of cytotoxicity already after 24 h of treatment. The experimental data show that oxidative stress may be a key route in inducing the cytotoxicity of ZnO nanoparticles in colon carcinoma cells. Moreover, the study of the relationship between toxicological effects and physico-chemical characteristics of particles suggests that surface area does not play a primary role in the cytotoxicity.

De Berardis, Barbara; Civitelli, Gabriele; Condello, Maria; Lista, Pasquale; Pozzi, Roberta; Arancia, Giuseppe [Department of Technology and Health, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome (Italy); Meschini, Stefania, E-mail: stefania.meschini@iss.i [Department of Technology and Health, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome (Italy)

2010-08-01

4

Copper Oxide Nanoparticles Induce Oxidative Stress and Cytotoxicity in Airway Epithelial Cells  

PubMed Central

Metal oxide nanoparticles are often used as industrial catalysts and elevated levels of these particles have been clearly demonstrated at sites surrounding factories. To date, limited toxicity data on metal oxide nanoparticles are available. To understand the impact of these airborne pollutants on the respiratory system, airway epithelial (HEp-2) cells were exposed to increasing doses of silicon oxide (SiO2), ferric oxide (Fe2O3) and copper oxide (CuO) nanoparticles, the leading metal oxides found in ambient air surrounding factories. CuO induced the greatest amount of cytotoxicity in a dose dependent manner; while even high doses (400 µg/cm2) of SiO2 and Fe2O3 were non-toxic to HEp-2 cells. Although all metal oxide nanoparticles were able to generate ROS in HEp-2 cells, CuO was better able to overwhelm antioxidant defenses (e.g. catalase and glutathione reductase). A significant increase in the level of 8-isoprostanes and in the ratio of GSSG to total glutathione in cells exposed to CuO suggested that ROS generated by CuO induced oxidative stress in HEp-2 cells. Co-treatment of cells with CuO and the antioxidant resveratrol increased cell viability suggesting that oxidative stress may be the cause of the cytotoxic effect of CuO. These studies demonstrated that there is a high degree of variability in the cytotoxic effects of metal oxides, that this variability is not due to the solubility of the transition metal, and that this variability appears to involve sustained oxidative stress possibly due to redox cycling. PMID:19699289

Fahmy, Baher; Cormier, Stephania A.

2009-01-01

5

Radiofrequency field-induced thermal cytotoxicity in cancer cells treated with fluorescent nanoparticles  

PubMed Central

Background Non-ionizing radiation, such as radiofrequency (RF) field and near infrared laser, induces thermal cytotoxicity in cancer cells treated with gold nanoparticles (AuNP). Quantum dots (QD) are fluorescent semiconducting nanoparticles that we hypothesize will induce similar injury following RF field irradiation. Methods AuNP and two types of QD (cadmium-selenide and indium-gallium-phosphide) conjugated to cetuximab (C225), a monoclonal antibody against human epidermal growth factor receptor (EGFR-1), demonstrated concentration-dependent heating in a RF field. We investigated the effect of RF field exposure after targeted nanoparticle treatment in a co-culture of two human cancer cell lines that have differential EGFR-1 expression (a high expressing pancreatic carcinoma, Panc-1, and a low expressing breast carcinoma, Cama-1). Results RF exposed Panc-1 or Cama-1 cells not containing AuNP or QD had a viability greater than 92%. The viability of Panc-1 cells exposed to the RF field after treatment with 50 nM Au-C225 was 39.4% ± 8.3% without injury to bystander Cama-1 cells (viability was 93.7% ± 1.0%, p ~ 0.0006). Panc-1 cells treated with targeted Cd-Se QD were only 47.5% viable after RF field exposure (p < 0.0001 compared to RF only Panc-1 control cells). Targeted InGaP QD decreased Panc-1 viability to 58.2% ± 3.4% after RF field exposure (p ~ 0.0004 compared to Cama-1 and Panc-1 controls). Conclusion We selectively induced RF field cytotoxicity in Panc-1 cells without injury to bystander Cama-1 cells utilizing EGFR-1 targeted nanoparticles, and demonstrated an interesting bifunctionality of fluorescent nanoparticles as agents for both cancer cell imaging and treatment. PMID:20564640

Glazer, Evan S.; Curley, Steven A.

2010-01-01

6

Gold Nanoparticles Cytotoxicity  

NASA Astrophysics Data System (ADS)

Over the last two decades gold nanoparticles (AuNPs) have been used for many scientific applications and have attracted attention due to the specific chemical, electronic and optical size dependent properties that make them very promising agents in many fields such as medicine, imagine techniques and electronics. More specifically, biocompatible gold nanoparticles have a huge potential for use as the contrast augmentation agent in X-ray Computed Tomography and Photo Acoustic Tomography for early tumor diagnostic as well these nanoparticles are extensively researched for enhancing the targeted cancer treatment effectiveness such as photo-thermal and radiotherapy. In most biomedical applications biocompatible gold nanoparticles are labeled with specific tumor or other pathology targeting antibodies and used for site specific drug delivery. However, even though gold nanoparticles poses very high level of anti cancer properties, the question of their cytotoxicity ones they are released in normal tissue has to be researched. Moreover, the huge amount of industrially produced gold nanoparticles raises the question of these particles being a health hazard, since the penetration is fairly easy for the "nano" size substances. This study focuses on the effect of AuNPs on a human skin tissue, since it is fall in both categories -- the side effects for biomedical applications and industrial workers and users' exposure during production and handling. Therefore, in the present project, gold nanoparticles stabilized with the biocompatible agent citric acid were generated and characterized by Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The cytotoxic effect of AuNPs release to healthy skin tissue was modeled on 3 different cell types: human keratinocytes, human dermal fibroblasts, and human adipose derived stromal (ADS) cells. The AuNPs localization inside the cell was found to be cell type dependent. Overall cytotoxicity was found to be dependent on time, concentration and nanoparticle size. Additionally, the question of cell recovery once the source of AuNPs is removed was investigated in the present work. It was found that full cell functions recovery is possible after removing the source of nanoparticles.

Mironava, Tatsiana

7

Amyloid fibrils enhance transport of metal nanoparticles in living cells and induced cytotoxicity.  

PubMed

Amyloid protein fibrils occur in vivo as pathological agents, in the case of neurodegenerative diseases, or as functional amyloids, when playing biologically vital roles. Here we show how amyloid fibrils generated from a food protein, ?-lactoglobulin, can be used as nanoreactors for the synthesis of metal nanoparticles and demonstrate that the resulting hybrids can play a central role in the internalization of nanoparticles into living cells, with up to 3-fold-enhanced transport properties over pristine nanoparticles. We conjugate gold, silver, and palladium nanoparticles onto amyloid fibrils by chemical reduction, and we study their effect on dendritic and MCF7 breast cancer cells. Transmission electron microscopy indicates localization of nanoparticles inside vesicles of the cells. Flow cytometry reveals that silver nanoparticle-amyloid hybrids are cytotoxic, while gold and palladium nanoparticle-amyloid hybrids produce no notable effect on cell viability and activation status. PMID:24941321

Bolisetty, Sreenath; Boddupalli, Chandra Sekhar; Handschin, Stephan; Chaitanya, Krishna; Adamcik, Jozef; Saito, Yasuyuki; Manz, Markus G; Mezzenga, Raffaele

2014-07-14

8

Cytotoxic Effects of Fucoidan Nanoparticles against Osteosarcoma  

PubMed Central

In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell line more efficiently than native fucoidan. The more potent effects of nanoparticle fucoidan, relative to native fucoidan, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell transport studies showed that permeation of nanoparticle fucoidan was higher than native fucoidan. The higher bioactivity and superior bioavailability of nanoparticle fucoidan could potentially be utilized to develop novel therapies for osteosarcoma. PMID:24177673

Kimura, Ryuichiro; Rokkaku, Takayoshi; Takeda, Shinji; Senba, Masachika; Mori, Naoki

2013-01-01

9

Noninvasive radiofrequency field-induced hyperthermic cytotoxicity in human cancer cells using cetuximab-targeted gold nanoparticles.  

PubMed

Shortwave (MHz range) radiofrequency (RF) energy is nonionizing, penetrates deeply into biologic tissues with no adverse side effects, and heats gold nanoparticles efficiently. Targeted delivery of gold nanoparticles to cancer cells should result in hyperthermic cytotoxicity upon exposure to a focused, noninvasive RF field. In this report we demonstrate that gold nanoparticles conjugated with cetuximab (C225) are quickly internalized by Panc-1 (pancreatic adenocarcinoma) and Difi (colorectal adenocarcinoma) cancer cells overexpressing epidermal growth factor receptor (EGFR). Panc-1 or Difi cells treated with naked gold nanoparticles or nonspecific IgG-conjugated gold nanoparticles demonstrated minimal intracellular uptake of gold nanoparticles by transmission electron microscopy (TEM). In contrast, there were dense concentrations of cytoplasmic vesicles containing gold nanoparticles following treatment with cetuximab-conjugated gold nanoparticles. Exposure of cells to a noninvasive RF field produced nearly 100% cytotoxicity in cells treated with the cetuximab-conjugated gold nanoparticles, but significantly lower levels of cytotoxicity in the two control groups (P < 0.00012). Treatment of a breast cancer cell line (CAMA-1) that does not express EGFR with cetuximab-conjugated gold nanoparticles produced no enhanced cytotoxicity following treatment in the RF field. Conjugation of cancer cell-directed targeting agents to gold nanoparticles may represent an effective and cancer-specific therapy to treat numerous types of human malignant disease using noninvasive RF hyperthermia. PMID:19227011

Curley, Steven A; Cherukuri, Paul; Briggs, Katrina; Patra, Chitta Ranjan; Upton, Mark; Dolson, Elisa; Mukherjee, Priyabrata

2008-01-01

10

Activation of Erk and p53 regulates copper oxide nanoparticle-induced cytotoxicity in keratinocytes and fibroblasts.  

PubMed

Copper oxide nanoparticles (CuONP) have attracted increasing attention due to their unique properties and have been extensively utilized in industrial and commercial applications. For example, their antimicrobial capability endows CuONP with applications in dressings and textiles against bacterial infections. Along with the wide applications, concerns about the possible effects of CuONP on humans are also increasing. It is crucial to evaluate the safety and impact of CuONP on humans, and especially the skin, prior to their practical application. The potential toxicity of CuONP to skin keratinocytes has been reported recently. However, the underlying mechanism of toxicity in skin cells has remained unclear. In the present work, we explored the possible mechanism of the cytotoxicity of CuONP in HaCaT human keratinocytes and mouse embryonic fibroblasts (MEF). CuONP exposure induced viability loss, migration inhibition, and G2/M phase cycle arrest in both cell types. CuONP significantly induced mitogen-activated protein kinase (extracellular signal-regulated kinase [Erk], p38, and c-Jun N-terminal kinase [JNK]) activation in dose- and time-dependent manners. U0126 (an inhibitor of Erk), but not SB 239063 (an inhibitor of p38) or SP600125 (an inhibitor of JNK), enhanced CuONP-induced viability loss. CuONP also induced decreases in p53 and p-p53 levels in both cell types. Cyclic pifithrin-?, an inhibitor of p53 transcriptional activity, enhanced CuONP-induced viability loss. Nutlin-3?, a p53 stabilizer, prevented CuONP-induced viability loss in HaCaT cells, but not in MEF cells, due to the inherent toxicity of nutlin-3? to MEF. Moreover, the experiments on primary keratinocytes are in accordance with the conclusions acquired from HaCaT and MEF cells. These data demonstrate that the activation of Erk and p53 plays an important role in CuONP-induced cytotoxicity, and agents that preserve Erk or p53 activation may prevent CuONP-induced cytotoxicity. PMID:25336953

Luo, Cheng; Li, Yan; Yang, Liang; Zheng, Yan; Long, Jiangang; Jia, Jinjing; Xiao, Shengxiang; Liu, Jiankang

2014-01-01

11

Activation of Erk and p53 regulates copper oxide nanoparticle-induced cytotoxicity in keratinocytes and fibroblasts  

PubMed Central

Copper oxide nanoparticles (CuONP) have attracted increasing attention due to their unique properties and have been extensively utilized in industrial and commercial applications. For example, their antimicrobial capability endows CuONP with applications in dressings and textiles against bacterial infections. Along with the wide applications, concerns about the possible effects of CuONP on humans are also increasing. It is crucial to evaluate the safety and impact of CuONP on humans, and especially the skin, prior to their practical application. The potential toxicity of CuONP to skin keratinocytes has been reported recently. However, the underlying mechanism of toxicity in skin cells has remained unclear. In the present work, we explored the possible mechanism of the cytotoxicity of CuONP in HaCaT human keratinocytes and mouse embryonic fibroblasts (MEF). CuONP exposure induced viability loss, migration inhibition, and G2/M phase cycle arrest in both cell types. CuONP significantly induced mitogen-activated protein kinase (extracellular signal-regulated kinase [Erk], p38, and c-Jun N-terminal kinase [JNK]) activation in dose- and time-dependent manners. U0126 (an inhibitor of Erk), but not SB 239063 (an inhibitor of p38) or SP600125 (an inhibitor of JNK), enhanced CuONP-induced viability loss. CuONP also induced decreases in p53 and p-p53 levels in both cell types. Cyclic pifithrin-?, an inhibitor of p53 transcriptional activity, enhanced CuONP-induced viability loss. Nutlin-3?, a p53 stabilizer, prevented CuONP-induced viability loss in HaCaT cells, but not in MEF cells, due to the inherent toxicity of nutlin-3? to MEF. Moreover, the experiments on primary keratinocytes are in accordance with the conclusions acquired from HaCaT and MEF cells. These data demonstrate that the activation of Erk and p53 plays an important role in CuONP-induced cytotoxicity, and agents that preserve Erk or p53 activation may prevent CuONP-induced cytotoxicity. PMID:25336953

Luo, Cheng; Li, Yan; Yang, Liang; Zheng, Yan; Long, Jiangang; Jia, Jinjing; Xiao, Shengxiang; Liu, Jiankang

2014-01-01

12

Cytotoxic Potential of Silver Nanoparticles  

PubMed Central

Silver nanoparticles (AgNPs) have been widely used in industrial, household, and healthcare-related products due to their excellent antimicrobial activity. With increased exposure of AgNPs to human beings, the risk of safety has attracted much attention from the public and scientists. In review of recent studies, we discuss the potential impact of AgNPs on individuals at the cell level. In detail, we highlight the main effects mediated by AgNPs on the cell, such as cell uptake and intracellular distribution, cytotoxicity, genotoxicity, and immunological responses, as well as some of the major factors that influence these effects in vivo and in vivo, such as dose, time, size, shape, surface chemistry, and cell type. At the end, we summarize the main influences on the cell and indicate the challenges in this field, which may be helpful for assessing the risk of AgNPs in future. PMID:24532494

Zhang, Tianlu; Wang, Liming

2014-01-01

13

Kinetics and pathogenesis of intracellular magnetic nanoparticle cytotoxicity  

NASA Astrophysics Data System (ADS)

Magnetic nanoparticles excited by alternating magnetic fields (AMF) have demonstrated effective tumor-specific hyperthermia. This treatment is effective as a monotherapy as well as a therapeutic adjuvant to chemotherapy and radiation. Iron oxide nanoparticles have been shown, so far, to be non-toxic, as are the exciting AMF fields when used at moderate levels. Although higher levels of AMF can be more effective, depending on the type of iron oxide nanoparticles use, these higher field strengths and/or frequencies can induce normal tissue heating and toxicity. Thus, the use of nanoparticles exhibiting significant heating at low AMF strengths and frequencies is desirable. Our preliminary experiments have shown that the aggregation of magnetic nanoparticles within tumor cells improves their heating effect and cytotoxicity per nanoparticle. We have used transmission electron microscopy to track the endocytosis of nanoparticles into tumor cells (both breast adenocarcinoma (MTG-B) and acute monocytic leukemia (THP-1) cells). Our preliminary results suggest that nanoparticles internalized into tumor cells demonstrate greater cytotoxicity when excited with AMF than an equivalent heat dose from excited external nanoparticles or cells exposed to a hot water bath. We have also demonstrated that this increase in SAR caused by aggregation improves the cytotoxicity of nanoparticle hyperthermia therapy in vitro.

Giustini, Andrew J.; Gottesman, Rachel E.; Petryk, A. A.; Rauwerdink, A. M.; Hoopes, P. Jack

2011-03-01

14

Enhanced cytotoxicity and apoptosis-induced anticancer effect of silibinin-loaded nanoparticles in oral carcinoma (KB) cells.  

PubMed

Silibinin (SIL) is a plant derived flavonoid isolated from the fruits and seeds of the milk thistle (Silybum marianum). Silibinin possesses a wide variety of biological applications including anticancer activities but poor aqueous solubility and poor bioavailability limit its potential and efficacy at the tumor sites. In the present study, silibinin was encapsulated in Eudragit® E (EE) nanoparticles in the presence of stabilizing agent polyvinyl alcohol (PVA) and its anticancer efficacy in oral carcinoma (KB) cells was studied. Silibinin loaded nanoparticles (SILNPs) were prepared by nanoprecipitation technique and characterized in terms of size distribution, morphology, surface charge, encapsulation efficiency and in vitro drug release. MTT assay revealed higher cytotoxic efficacy of SILNPs than free SIL in KB cells. Meanwhile, reactive oxygen species (ROS) determination revealed the significantly higher intracellular ROS levels in SILNPs treated cells compared to free SIL treated cells. Therefore, the differential cytotoxicity between SILNPs and SIL may be mediated by the discrepancy of intracellular ROS levels. Moreover, acridine orange (AO) and ethidium bromide (EB) dual staining and reduced mitochondrial membrane potential (MMP) confirmed the induction of apoptosis with nanoparticle treatment. Further, the extent of DNA damage (evaluated by comet assay) was significantly increased in SILNPs than free SIL in KB cells. Taken together, the present study suggests that silibinin-loaded nanoparticles can be used as an effective drug delivery system to produce a better chemopreventive response for the treatment of cancer. PMID:24907761

Gohulkumar, M; Gurushankar, K; Rajendra Prasad, N; Krishnakumar, N

2014-08-01

15

Selective cytotoxic effect of ZnO nanoparticles on glioma cells  

Microsoft Academic Search

In this study we examined the cytotoxic effect of ZnO nanoparticles on various human cancer and normal cells. We found that\\u000a the ZnO nanoparticles exerted a cytotoxic effect on the human glioma cell lines A172, U87, LNZ308, LN18, and LN229, whereas\\u000a no cytotoxic effect was observed on normal human astrocytes. Similarly, the ZnO nanoparticles induced cell death in breast\\u000a and

Stella Ostrovsky; Gila Kazimirsky; Aharon Gedanken; Chaya Brodie

2009-01-01

16

Cytotoxicity and ion release of alloy nanoparticles.  

PubMed

It is well-known that nanoparticles could cause toxic effects in cells. Alloy nanoparticles with yet unknown health risk may be released from cardiovascular implants made of Nickel-Titanium or Cobalt-Chromium due to abrasion or production failure. We show the bio-response of human primary endothelial and smooth muscle cells exposed to different concentrations of metal and alloy nanoparticles. Nanoparticles having primary particle sizes in the range of 5-250 nm were generated using laser ablation in three different solutions avoiding artificial chemical additives, and giving access to formulations containing nanoparticles only stabilized by biological ligands. Endothelial cells are found to be more sensitive to nanoparticle exposure than smooth muscle cells. Cobalt and Nickel nanoparticles caused the highest cytotoxicity. In contrast, Titanium, Nickel-Iron, and Nickel-Titanium nanoparticles had almost no influence on cells below a nanoparticle concentration of 10 ?M. Nanoparticles in cysteine dissolved almost completely, whereas less ions are released when nanoparticles were stabilized in water or citrate solution. Nanoparticles stabilized by cysteine caused less inhibitory effects on cells suggesting cysteine to form metal complexes with bioactive ions in media. PMID:22448125

Hahn, Anne; Fuhlrott, Jutta; Loos, Anneke; Barcikowski, Stephan

2012-01-01

17

Cytotoxicity assessment of heparin nanoparticles in NR8383 macrophages.  

PubMed

The bioavailability of low molecular weight heparin (LMWH) has been increased by encapsulation in nanoparticles. As a complement to these results, the cytotoxicity and apoptosis induced by LMWH nanoparticles prepared by two methods [nanoprecipitation (NP) and double emulsion (DE)] using Eudragit RS (RS) and poly-epsilon-caprolactone (PCL) have been analysed. Particle sizes varied from 54 to 400nm with zeta potential values between -65 and +63mV. Our results showed that the method of nanoparticle preparation affects their properties, especially in terms of drug incorporation and cell tolerance. Cell viability ranged from 6% to 100% depending on the preparation method and physicochemical properties of the particles and the type of toxicity assay. Particle diameter and zeta potential seemed to be the most valuable cytotoxicity markers when cell viability was measured by Trypan blue exclusion and MTT respectively. Nanoparticles prepared by DE were better tolerated than those of NP. LMWH encapsulation into the cationic nanoparticles reduces remarkably their toxicity. Apoptosis evaluation showed activated caspases in exposed cells. However, no nuclear fragmentation was detected in NR8383 cells whatever the tested nanoparticles. DE nanoparticles of RS and PCL can be proposed as a good LMWH delivery system due to their low toxicity (IC(50) approximately 2.33 and 0.96mg/mL, respectively). PMID:20542101

Eidi, H; Joubert, O; Attik, G; Duval, R E; Bottin, M C; Hamouia, A; Maincent, P; Rihn, B H

2010-08-30

18

Experimental considerations on the cytotoxicity of nanoparticles  

PubMed Central

Engineered nanoparticles are one of the leading nanomaterials currently under investigation due to their applicability in various fields, including drug and gene delivery, biosensors, cancer treatment and diagnostic tools. Moreover, the number of commercial products containing nanoparticles released on the market is rapidly increasing. Nanoparticles are already widely distributed in air, cosmetics, medicines and even in food. Therefore, the unintended adverse effect of nanoparticle exposure is a growing concern both academically and socially. In this context, the toxicity of nanoparticles has been extensively studied; however, several challenges are encountered due to the lack of standardized protocols. In order to improve the experimental conditions of nanoparticle toxicity studies, serious consideration is critical to obtain reliable and realistic data. The cell type must be selected considering the introduction route and target organ of the nanoparticle. In addition, the nanoparticle dose must reflect the realistic concentration of nanoparticles and must be loaded as a well-dispersed form to observe the accurate size- and shape-dependent effect. In deciding the cytotoxicity assay method, it is important to choose the appropriate method that could measure the toxicity of interest without the false-negative or -positive misinterpretation of the toxicity result. PMID:21793681

Kong, Bokyung; Seog, Ji Hyun; Graham, Lauren M; Lee, Sang Bok

2011-01-01

19

Cytotoxicity and genotoxicity of biogenic silver nanoparticles  

NASA Astrophysics Data System (ADS)

Biogenic silver nanoparticles with 40.3 ± 3.5 nm size and negative surface charge (- 40 mV) were prepared with Fusarium oxysporum. The cytotoxicity of 3T3 cell and human lymphocyte were studied by a TaliTM image-based cytometer and the genotoxicity through Allium cepa and comet assay. The results of BioAg-w (washed) and BioAg-nw (unwashed) biogenic silver nanoparticles showed cytotoxicity exceeding 50 ?g/mL with no significant differences of response in 5 and 10 ?g/mL regarding viability. Results of genotoxicity at concentrations 5.0 and 10.0 ug/mL show some response, but at concentrations 0.5 and 1.0 ?g/mL the washed and unwashed silver nanoparticles did not present any effect. This in an important result since in tests with different bacteria species and strains, including resistant, MIC (minimal inhibitory concentration) had good answers at concentrations less than 1.9 ?g/mL. This work concludes that biogenic silver nanoparticles may be a promising option for antimicrobial use in the range where no cyto or genotoxic effect were observed. Furthermore, human cells were found to have a greater resistance to the toxic effects of silver nanoparticles in comparison with other cells.

Lima, R.; Feitosa, L. O.; Ballottin, D.; Marcato, P. D.; Tasic, L.; Durán, N.

2013-04-01

20

Zinc sulfide nanoparticles selectively induce cytotoxic and genotoxic effects on leukemic cells: involvement of reactive oxygen species and tumor necrosis factor alpha.  

PubMed

The aim of the present study was to develop zinc sulfide nanoparticles (ZnS NPs) and to study their cytotoxicity against the KG-1A (human acute myeloid leukemia) cell line. ZnS NPs were synthesized using the pyrolytic method and characterized by X-ray diffraction, dynamic light scattering, surface zeta potential, scanning electron microscopy and atomic force microscopy. Cell viability study and flow cytometric analysis confirmed the potent cytotoxic effects of ZnS NPs on cancer cells in a dose-dependent fashion. Successful uptakes of ZnS NPs by leukemic cells were confirmed by phase contrast fluorescence microscopy. pH-dependent dissolution of ZnS NPs was done using atomic absorption microscopy to understand the cell-specific internalization of Zn(+) . This internalization of NPs facilitated the generation of excess reactive oxygen species (ROS), followed by tumor necrosis factor alpha (TNF-?) secretion which caused severe DNA damage as observed in the comet assay and altered the mitochondrial membrane potential (MMP) in leukemic cells. Surprisingly ZnS NPs had no toxic effects on normal lymphocytes at doses up to 50 µg ml(-1) . Pre-treatment with ROS and TNF-? inhibitor confirmed that these nanoparticles were able to kill leukemic cells by generating an excess amount of ROS and thereby initiated TNF-? mediated apoptosis pathway. These findings clarify the mechanism with which ZnS NPs induced anticancer activities in vitro. To elicit its utilities and its application to cancer treatment in vivo is under investigation. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24477783

Dash, Sandeep Kumar; Ghosh, Totan; Roy, Soumyabrata; Chattopadhyay, Sourav; Das, Debasis

2014-11-01

21

The role of reactive oxygen species in silicon dioxide nanoparticle-induced cytotoxicity and DNA damage in HaCaT cells.  

PubMed

The increasing applications of silicon dioxide (SiO(2)) nanomaterials have been widely concerned over their biological effects and potential hazard to human health. In this study, we explored the effects of SiO(2) nanoparticles (15, 30, and 100 nm) and their micro-sized counterpart on cultured human epidermal Keratinocyte (HaCaT) cells. Cell viability, cell morphology, reactive oxygen species (ROS), DNA damage (8-OHdG, ?H2AX and comet assay) and apoptosis were assessed under control and SiO(2) nanoparticles exposed conditions. As observed in the Cell Counting Kit-8 (CCK-8) assay, exposure to 15, 30 or 100 nm SiO(2) nanoparticles at dosage levels between 0 and 100 ?g/ml decreased cell viability in a concentration- and size dependent manner and the IC50 of 24 hour exposure was 19.4 ± 1.3, 27.7 ± 1.5 and 35.9 ± 1.6 ?g/ml for 15, 30 and 100 nm SiO(2) nanoparticles, respectively. Morphological examination revealed cell shrinkage and cell wall missing after SiO(2) nanoparticle exposure. Increase in intracellular ROS level and DNA damage as well as apoptosis were also observed in SiO(2) nanoparticle-exposed HaCaT cells. Exposure to SiO(2) nanoparticles results in a concentration- and size-dependent cytotoxicity and DNA damage in cultural HaCaT cells which is closely correlated to increased oxidative stress. PMID:22179747

Gong, Chunmei; Tao, Gonghua; Yang, Linqing; Liu, Jianjun; He, Haowei; Zhuang, Zhixiong

2012-04-01

22

SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells  

PubMed Central

Background Nanometer silicon dioxide (nano-SiO2) has a wide variety of applications in material sciences, engineering and medicine; however, the potential cell biological and proteomic effects of nano-SiO2 exposure and the toxic mechanisms remain far from clear. Results Here, we evaluated the effects of amorphous nano-SiO2 (15-nm, 30-nm SiO2). on cellular viability, cell cycle, apoptosis and protein expression in HaCaT cells by using biochemical and morphological analysis, two-dimensional differential gel electrophoresis (2D-DIGE) as well as mass spectrometry (MS). We found that the cellular viability of HaCaT cells was significantly decreased in a dose-dependent manner after the treatment of nano-SiO2 and micro-sized SiO2 particles. The IC50 value (50% concentration of inhibition) was associated with the size of SiO2 particles. Exposure to nano-SiO2 and micro-sized SiO2 particles also induced apoptosis in HaCaT cells in a dose-dependent manner. Furthermore, the smaller SiO2 particle size was, the higher apoptotic rate the cells underwent. The proteomic analysis revealed that 16 differentially expressed proteins were induced by SiO2 exposure, and that the expression levels of the differentially expressed proteins were associated with the particle size. The 16 proteins were identified by MALDI-TOF-TOF-MS analysis and could be classified into 5 categories according to their functions. They include oxidative stress-associated proteins; cytoskeleton-associated proteins; molecular chaperones; energy metabolism-associated proteins; apoptosis and tumor-associated proteins. Conclusions These results showed that nano-SiO2 exposure exerted toxic effects and altered protein expression in HaCaT cells. The data indicated the alterations of the proteins, such as the proteins associated with oxidative stress and apoptosis, could be involved in the toxic mechanisms of nano-SiO2 exposure. PMID:20180970

2010-01-01

23

Comparative in vitro cytotoxicity study of silver nanoparticle on two mammalian cell lines.  

PubMed

In this study the cytotoxic effect of commercially available silver (Ag) nanoparticle was evaluated using human dermal and cervical cancer cell lines. Prior to the cellular studies a full particle size characterisation was carried out using Dynamic Light Scattering (DLS), Transmission Electron Microscopy and Scanning Electron Microscopy in distilled water and cell culture media. The Zeta Potential (ZP) associated with the Ag nanoparticle was also determined in order to assess its stability in the solutions and its possible interaction with the media. The DLS and ZP study have suggested interaction of Ag nanoparticles with the media, which can lead to secondary toxicity. The toxic effects of Ag nanoparticles were then evaluated using different cytotoxic endpoints namely the lysosomal activity, mitochondrial metabolism, basic cellular metabolism, cellular protein content and cellular proliferative capacity. The cytotoxic effect of Ag nanoparticle was dependant on dose, exposure time and on the cell line tested. Further investigation was carried out on HeLa and HaCaT cell lines to elucidate the mechanism of its cytotoxicity. The Ag nanoparticle was noted to induce elevated levels of oxidative stress, glutathione depletion and damage to the cell membrane as found from the adenylate kinase assay and that leads to the apoptosis. Overall, significant differences were observed between the sensitivity of the two cell lines which can be understood in terms of their natural antioxidant levels. PMID:22198051

Mukherjee, Sanchali Gupta; O'Claonadh, Niall; Casey, Alan; Chambers, Gordon

2012-03-01

24

Nanoparticle Incorporation of Melittin Reduces Sperm and Vaginal Epithelium Cytotoxicity  

PubMed Central

Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro. In the current study, we assessed the impact of blank and melittin-containing perfluorocarbon nanoparticles on sperm motility and the viability of both sperm and vaginal epithelial cells. We found that free melittin was toxic to sperm and vaginal epithelium at concentrations greater than 2 µM (p<0.001). However, melittin nanoparticles were not cytotoxic to sperm (p?=?0.42) or vaginal epithelium (p?=?0.48) at an equivalent melittin concentration of 10 µM. Thus, nanoparticle formulation of melittin reduced melittin cytotoxicity fivefold and prevented melittin toxicity at concentrations previously shown to inhibit HIV infectivity. Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin concentrations ?20 µM (p<0.001) and were toxic to sperm at equivalent melittin concentrations ?40 µM (p<0.001). Sperm cytotoxicity was enhanced by targeting of the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While further testing is needed to determine the extent of cytotoxicity in a more physiologically relevant model system, these results suggest that melittin-containing nanoparticles could form the basis of a virucide that is not toxic to sperm and vaginal epithelium. This virucide would be beneficial for HIV serodiscordant couples seeking to achieve natural pregnancy. PMID:24748389

Jallouk, Andrew P.; Moley, Kelle H.; Omurtag, Kenan; Hu, Grace; Lanza, Gregory M.; Wickline, Samuel A.; Hood, Joshua L.

2014-01-01

25

Evaluation of cytotoxicity of polypyrrole nanoparticles synthesized by oxidative polymerization.  

PubMed

Polypyrrole (Ppy) is known as biocompatible material, which is used in some diverse biomedical applications and seeming to be a very promising for advanced biotechnological applications. In order to increase our understanding about biocompatibility of Ppy, in this study pure Ppy nanoparticles (Ppy-NPs) of fixed size and morphology were prepared by one-step oxidative polymerization and their cyto-compatibility was evaluated. The impact of different concentration of Ppy nanoparticles on primary mouse embryonic fibroblasts (MEF), mouse hepatoma cell line (MH-22A), and human T lymphocyte Jurkat cell line was investigated. Cell morphology, viability/proliferation after the treatment by Ppy nanoparticles was evaluated. Obtained results showed that Ppy nanoparticles at low concentrations are biocompatible, while at high concentrations they became cytotoxic for Jurkat, MEF and MH-22A cells, and it was found that cytotoxic effect is dose-dependent. PMID:23454454

Vaitkuviene, Aida; Kaseta, Vytautas; Voronovic, Jaroslav; Ramanauskaite, Giedre; Biziuleviciene, Gene; Ramanaviciene, Almira; Ramanavicius, Arunas

2013-04-15

26

Nanoparticle drug delivery enhances the cytotoxicity of hydrophobichydrophilic drug conjugates  

E-print Network

Nanoparticle drug delivery enhances the cytotoxicity of hydrophobic­hydrophilic drug conjugates, Accepted 4th October 2011 DOI: 10.1039/c1jm13834k We report a drug conjugation approach to concurrently load both hydrophobic and hydrophilic drugs into the same drug delivery nanocarrier in a precisely

Zhang, Liangfang

27

The Influences of Cell Type and ZnO Nanoparticle Size on Immune Cell Cytotoxicity and Cytokine Induction  

NASA Astrophysics Data System (ADS)

Nanotechnology represents a new and enabling platform that promises to provide a range of innovative technologies for biological applications. ZnO nanoparticles of controlled size were synthesized, and their cytotoxicity toward different human immune cells evaluated. A differential cytotoxic response between human immune cell subsets was observed, with lymphocytes being the most resistant and monocytes being the most susceptible to ZnO nanoparticle-induced toxicity. Significant differences were also observed between previously activated memory lymphocytes and naive lymphocytes, indicating a relationship between cell-cycle potential and nanoparticle susceptibility. Mechanisms of toxicity involve the generation of reactive oxygen species, with monocytes displaying the highest levels, and the degree of cytotoxicity dependent on the extent of nanoparticle interactions with cellular membranes. An inverse relationship between nanoparticle size and cytotoxicity, as well as nanoparticle size and reactive oxygen species production was observed. In addition, ZnO nanoparticles induce the production of the proinflammatory cytokines, IFN-?, TNF-?, and IL-12, at concentrations below those causing appreciable cell death. Collectively, these results underscore the need for careful evaluation of ZnO nanoparticle effects across a spectrum of relevant cell types when considering their use for potential new nanotechnology-based biological applications.

Hanley, Cory; Thurber, Aaron; Hanna, Charles; Punnoose, Alex; Zhang, Jianhui; Wingett, Denise G.

2009-12-01

28

Selective cytotoxicity effect of cerium oxide nanoparticles under UV irradiation.  

PubMed

During photodynamic therapy (PDT) of cancers, there are numerous side effects, accompanied by damage to normal cells/tissues caused by the abnormal elevation of reactive oxygen species (ROS). In this paper, we aim to provide an effective method to reduce the relevant side effects of PDT by using cerium oxide nanoparticles. The well-dispersed poly(vinyl pyrrolidone) stabilized cerium oxide nanoparticles were successfully synthesized by using a one-pot method at 60 degrees C in slightly alkaline environment. The morphological and structural characterizations clearly illustrate the excellent lattice structures of cerium oxide, nanoparticles. The MTT assay indicates that these cerium oxide nanoparticles show no intrinsic cytotoxicity even at a concentration up to 300 micro g/mL. More importantly, the results demonstrate that these nanoparticles can selectively protect human normal cells but not the cancer cells from ROS damage after exposure to UV-radiation, suggesting their potential applications for PDT treatment. The rationale behind the selective protection effect can be attributed to the hindrance of the Ce (III)/Ce (IV) redox reaction cycle on the surface of cerium oxide nanoparticles due to the abnormal intracellular pH in cancer cells. Furthermore, these cerium oxide nanoparticles can be used as effective drug carriers for enhancing drug delivery efficiency to target cancer cells like hepatoma HepG2 cells. This raises the possibility of applying cerium oxide nanoparticles for multifunctional therapeutic applications, i.e., combination of efficient PDT and chemotherapy. PMID:24738336

Zhang, Li; Jiang, Hui; Selke, Matthias; Wang, Xuemei

2014-02-01

29

Microsomal Glutathione Transferase 1 Protects Against Toxicity Induced by Silica Nanoparticles but Not by Zinc Oxide Nanoparticles  

PubMed Central

Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO2, CeO2, SiO2, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO2 and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO2 and CeO2. We also noted pronounced cytotoxicity for three out of four additional SiO2 nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO2 nanoparticles tested and for one of the supplementary SiO2 nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO2 nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn2+ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn2+ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO2 nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum. PMID:22303956

2012-01-01

30

Cytotoxic and genotoxic characterization of titanium dioxide, gadolinium oxide, and poly(lactic-co-glycolic acid) nanoparticles in human fibroblasts.  

PubMed

Engineered nanomaterials have become prevalent in our everyday life. While the popularity of using nanomaterials in consumer products continues to rise, increasing awareness of nanotoxicology has also fuelled efforts to accelerate our understanding of the ill effects that different nanomaterials can bring to biological systems. In this study, we investigated the potential cytotoxicity and genotoxicity of three nanoparticles: titanium dioxide (TiO(2)), terbium-doped gadolinium oxide (Tb-Gd(2)O(3)), and poly(lactic-co-glycolic acid) (PLGA). To evaluate nanoparticle-induced genotoxicity more realistically, a human skin fibroblast cell line (BJ) with less mutated genotype compared with cancer cell line was used. The nanoparticles were first characterized by size, morphology, and surface charge. Cytotoxicity effects of the nanoparticles were then evaluated by monitoring the proliferation of treated BJ cells. Genotoxic influence was ascertained by profiling DNA damage via detection of ?H2AX expression. Our results suggested that both TiO(2) and Tb-Gd(2)O(3) nanoparticles induced cytotoxicity in a dose dependent way on BJ cells. These two nanomaterials also promoted genotoxicity via DNA damage. On the contrary, PLGA nanoparticles did not induce significant cytotoxic or genotoxic effects on BJ cells. PMID:22927021

Setyawati, Magdiel Inggrid; Khoo, Pheng Kian Stella; Eng, Bao Hui; Xiong, Sijing; Zhao, Xinxin; Das, Gautom Kumar; Tan, Timothy Thatt-Yang; Loo, Joachim Say Chye; Leong, David Tai; Ng, Kee Woei

2013-03-01

31

In Vitro Cytotoxicity of Nanoparticles in Mammalian Germline Stem Cells  

PubMed Central

Gametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals. Many chemicals have a negative impact on the germline, either by directly affecting the germ cells, or indirectly through their action on the somatic nursing cells. Ultimately, these effects can inhibit fertility, and they may have negative consequences for the development of the offspring. Recently, nanomaterials such as nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots have received enormous national attention in the creation of new types of analytical tools for biotechnology and the life sciences. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health and the environment. Thus, there are limited studies available on toxicity of nanoparticles for risk assessment of nanomaterials. The purpose of this study was to assess the suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity in the male germline in vitro. The effects of different types of nanoparticles on these cells were evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. Our results demonstrate a concentration-dependent toxicity for all types of particles tested, whereas the corresponding soluble salts had no significant effect. Silver nanoparticles were the most toxic while molybdenum trioxide (MoO3) nanoparticles were the least toxic. Our results suggest that this cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro. PMID:16014736

Braydich-Stolle, Laura; Hussain, Saber; Schlager, John J.; Hofmann, Marie-Claude

2010-01-01

32

In vitro evaluation of cytotoxicity of engineered metal oxide nanoparticles  

Microsoft Academic Search

The recent advances in nanotechnology and the corresponding popular usage of nanomaterials have resulted in uncertainties regarding their environmental impacts. In this study, we used a systematic approach to study and compare the in vitro cytotoxicity of selected engineered metal oxide nanoparticles to the test organisms — E. coli. Among the seven test nano-sized metal oxides, ZnO, CuO, Al2O3, La2O3,

Xiaoke Hu; Sean Cook; Peng Wang; Huey-min Hwang

2009-01-01

33

The mechanism of asbestos-induced cytotoxicity  

SciTech Connect

Crocidolite asbestos fibers constitute a serious environmental pollutant capable of causing pleural scarring and cancer. This thesis addresses three questions: (1) what is the mechanism of asbestos-induced cytotoxicity in vitro and in vivo (2) What is the influence of fiber size on cytotoxicity in vitro and in vivo (3) What is the chronic response of the peritoneal cavity to asbestos fibers of varying lengths Macrophages release reactive oxygen metabolites when exposed to crocidolite in vitro or in vivo. Crocidolite-induced cytotoxicity is prevented with superoxide dismutase (SOD) and catalase. In addition, presoaking crocidolite fibers in deferoxamine, prevents cytotoxicity in vitro and in vivo. In vitro, macrophages exposed to crocidolite also lose mitochondrial membrane potential and undergo lipid peroxidation. Neither of these changes in itself, however, is responsible for macrophage death. We also examined the role of crocidolite fiber size in cytoxicity. Both long and short crocidolite fibers are toxic to macrophages in vitro via an oxidant dependent mechanism. Within the periotoneal cavity long crocidolite fibers are acutely cytotoxic and inflammatory while short fibers are not. Weekly intraperitoneal injections of long and native crocidolite asbestos fibers produced mesotheliomas in 20-40% of mice after 35-50 weeks. Neoplastic and preneoplastic cells were obtained from these mice, cultured, and characterized for in vitro transformation and in vivo tumorigenicity.

Goodglick, L.A.

1988-01-01

34

Alloantibody-induced cytotoxicity of macrophages.  

PubMed

Alloantibodies substantially alter the in vitro nonspecific cytotoxic effect of macrophages on bystanding allogeneic and xenogeneic target cells. Although the specific IgM alloantibody increased significantly the ability to parental macrophages to damage target cells, IgG alloantibody had an opposite effect and suppressed the macrophage cytotoxicity. Macrophages of F1 hybrid mice were less affected by this treatment unless alloantibodies against both parental strains were added together. Parental macrophages exposed in vitro to the concomitant action of both IgM and IgG alloantibodies exhibited a diminished cytotoxicity toward target cells. It is proposed that IgM and IgG alloantibodies induce different conformational changes of the macrophage surface. PMID:1151077

Ptak, W; Hanczakowska, M

1975-09-01

35

Reducing ZnO nanoparticle cytotoxicity by surface modification  

NASA Astrophysics Data System (ADS)

Nanoparticulate zinc oxide (ZnO) is one of the most widely used engineered nanomaterials and its toxicology has gained considerable recent attention. A key aspect for controlling biological interactions at the nanoscale is understanding the relevant nanoparticle surface chemistry. In this study, we have determined the disposition of ZnO nanoparticles within human immune cells by measurement of total Zn, as well as the proportions of extra- and intracellular dissolved Zn as a function of dose and surface coating. From this mass balance, the intracellular soluble Zn levels showed little difference in regard to dose above a certain minimal level or to different surface coatings. PEGylation of ZnO NPs reduced their cytotoxicity as a result of decreased cellular uptake arising from a minimal protein corona. We conclude that the key role of the surface properties of ZnO NPs in controlling cytotoxicity is to regulate cellular nanoparticle uptake rather than altering either intracellular or extracellular Zn dissolution.Nanoparticulate zinc oxide (ZnO) is one of the most widely used engineered nanomaterials and its toxicology has gained considerable recent attention. A key aspect for controlling biological interactions at the nanoscale is understanding the relevant nanoparticle surface chemistry. In this study, we have determined the disposition of ZnO nanoparticles within human immune cells by measurement of total Zn, as well as the proportions of extra- and intracellular dissolved Zn as a function of dose and surface coating. From this mass balance, the intracellular soluble Zn levels showed little difference in regard to dose above a certain minimal level or to different surface coatings. PEGylation of ZnO NPs reduced their cytotoxicity as a result of decreased cellular uptake arising from a minimal protein corona. We conclude that the key role of the surface properties of ZnO NPs in controlling cytotoxicity is to regulate cellular nanoparticle uptake rather than altering either intracellular or extracellular Zn dissolution. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00458b

Luo, Mingdeng; Shen, Cenchao; Feltis, Bryce N.; Martin, Lisandra L.; Hughes, Anthony E.; Wright, Paul F. A.; Turney, Terence W.

2014-05-01

36

Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells  

SciTech Connect

Published toxicology data on chitosan nanoparticles (NP) often lack direct correlation to the in situ size and surface characteristics of the nanoparticles, and the repeated NP assaults as experienced in chronic use. The aim of this paper was to breach these gaps. Chitosan nanoparticles synthesized by spinning disc processing were characterised for size and zeta potential in HBSS and EMEM at pHs 6.0 and 7.4. Cytotoxicity against the Caco-2 cells was evaluated by measuring the changes in intracellular mitochondrial dehydrogenase activity, TEER and sodium fluorescein transport data and cell morphology. Cellular uptake of NP was observed under the confocal microscope. Contrary to established norms, the collective data suggest that the in vitro cytotoxicity of NP against the Caco-2 cells was less influenced by positive surface charges than by the particle size. Particle size was in turn determined by the pH of the medium in which the NP was dispersed, with the mean size ranging from 25 to 333 nm. At exposure concentration of 0.1%, NP of 25 ± 7 nm (zeta potential 5.3 ± 2.8 mV) was internalised by the Caco-2 cells, and the particles were observed to inflict extensive damage to the intracellular organelles. Concurrently, the transport of materials along the paracellular pathway was significantly facilitated. The Caco-2 cells were, however, capable of recovering from such assaults 5 days following NP removal, although a repeat NP exposure was observed to produce similar effects to the 1st exposure, with the cells exhibiting comparable resiliency to the 2nd assault. -- Highlights: ? Chitosan nanoparticles reduced mitochondrial dehydrogenase activity. ? Cellular uptake of chitosan nanoparticles was observed. ? Chitosan nanoparticles inflicted extensive damage to the cell morphology. ? The transport of materials along the paracellular pathway was facilitated.

Loh, Jing Wen [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia)] [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia); Saunders, Martin [Centre for Microscopy, Characterisation and Analysis, University of Western Australia (Australia)] [Centre for Microscopy, Characterisation and Analysis, University of Western Australia (Australia); Lim, Lee-Yong, E-mail: lee.lim@uwa.edu.au [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia) [Laboratory for Drug Delivery, Pharmacy, Characterisation and Analysis, University of Western Australia (Australia); School of Biomedical, Biomolecular and Chemical Sciences, 35 Stirling Hwy, Crawley 6009 (Australia)

2012-08-01

37

Effect of size and processing method on the cytotoxicity of realgar nanoparticles in cancer cell lines  

PubMed Central

In this study, the effects of the size and Chinese traditional processing (including elutriation, water cleaning, acid cleaning, alkali cleaning) on realgar nanoparticles (RN)-induced antitumor activity in human osteosarcoma cell lines (MG-63) and hepatoma carcinoma cell lines (HepG-2) were investigated. The human normal liver cell line (L-02) was used as control. RN was prepared by high-energy ball milling technology. The results showed that with the assistance of sodium dodecyl sulfate, the size of realgar could be reduced to 127 nm after 12 hours’ ball milling. The surface charge was decreased from 0.83 eV to ?17.85 eV and the content of As2O3 clearly increased. Except for elutriation, the processing methods did not clearly change the size of the RN, but the content of As2O3 was reduced dramatically. In vitro MTT tests indicated that in the two cancer cell lines, RN cytotoxicity was more intense than that of the coarse realgar nanoparticles, and cytotoxicity was typically time- and concentration-dependent. Also, RN cytotoxicities in the HepG-2 and L-02 cells all increased with increasing milling time. Due to the reduction of the As2O3 content, water cleaning, acid cleaning, and alkali cleaning decreased RN cytotoxicity in HepG-2, but RN after elutriation, with the lowest As2O3 (3.5 mg/g) and the smallest size (109.3 nm), showed comparable cytotoxicity in HepG-2 to RN without treatment. Meanwhile, RN-induced cytotoxicity in L-02 cells was clearly reduced. Therefore, it can be concluded that RN may provide a strong antiproliferation effect in the MG-63 and HepG-2 cells. Elutriation processing is a suitable approach to limit the dangerous side-effects of As2O3, while maintaining the effectiveness of RN. PMID:21845047

Zhao, Weizhong; Lu, Xun; Yuan, Yuan; Liu, Changsheng; Yang, Baican; Hong, Hua; Wang, Guoying; Zeng, Fanyan

2011-01-01

38

Comparison of Iron Oxide Nanoparticle and Waterbath Hyperthermia Cytotoxicity  

PubMed Central

The development of medical grade iron oxide nanoparticles (IONP) has renewed interest in hyperthermia cancer therapy. Because of their modifiable size and heating capabilities under an AC magnetic field (alternating magnetic field, AMF), IONPs have the potential to damage or kill cells in a manner more therapeutically efficient than previous hyperthermia techniques. The use of IONPs in hyperthermia cancer therapy has prompted numerous questions regarding the cytotoxic mechanism associated with IONP heat therapy and if such mechanism is different (more or less effective) with respect to conventional hyperthermia techniques.

Ogden, JA; Tate, JA; Strawbridge, RR; Ivkov, R; Hoopes, PJ

2014-01-01

39

Synthesis, colloidal properties and cytotoxicity of biopolymer nanoparticles.  

PubMed

To characterize the physicochemical and biological stability of nanodevices suitable for biomedical applications, polylactic acid (PLA) nanoparticles (NPs) of 112?±?6 nm and polyhydroxy butyrate (PHB) of 15?±?5 nm size were prepared by standardizing the suitable method for each. Morphology of NPs was studied by scanning and transmission electron microscopy and temperature stability by thermogravimetric analysis. Their stability in biological fluids (simulated gastrointestinal and saliva) and tolerance against 0.5 mM NaCl were analyzed. PHB NPs remained stable in all fluids, while after 24 h treatment, the PLA NPs showed the beginning of disintegration with intestinal fluid mimic. In addition to the preparation of polyethylene glycol (PEG) surface-coated NPs, PLA-PEG-PLA triblock copolymer (MW???7,366 Da) was also chemically synthesized and characterized. Cytotoxicity of all forms of nanoparticles was tested by MTT assay and by annexin pi staining. PMID:25172058

Moorkoth, Dhanya; Nampoothiri, Kesavan Madhavan

2014-11-01

40

Quercetin-induced cardioprotection against doxorubicin cytotoxicity  

PubMed Central

Background Cancer has continually been the leading cause of death worldwide for decades. Thus, scientists have actively devoted themselves to studying cancer therapeutics. Doxorubicin is an efficient drug used in cancer therapy, but also produces reactive oxygen species (ROS) that induce severe cytotoxicity against heart cells. Quercetin, a plant-derived flavonoid, has been proven to contain potent antioxidant and anti-inflammatory properties. Thus, this in vitro study investigated whether quercetin can decrease doxorubicin-induced cytotoxicity and promote cell repair systems in cardiomyocyte H9C2 cells. Results Proteomic analysis and a cell biology assay were performed to investigate the quercetin-induced responses. Our data demonstrated that quercetin treatment protects the cardiomyocytes in a doxorubicin-induced heart damage model. Quercetin significantly facilitated cell survival by inhibiting cell apoptosis and maintaining cell morphology by rearranging the cytoskeleton. Additionally, 2D-DIGE combined with MALDI-TOF MS analysis indicated that quercetin might stimulate cardiomyocytes to repair damage after treating doxorubicin by modulating metabolic activation, protein folding and cytoskeleton rearrangement. Conclusion Based on a review of the literature, this study is the first to report detailed protective mechanisms for the action of quercetin against doxorubicin-induced cardiomyocyte toxicity based on in-depth cell biology and proteomic analysis. PMID:24359494

2013-01-01

41

Menadione-induced cytotoxicity to rat osteoblasts.  

PubMed

Oxygen-derived free radical injury has been associated with several cytopathic conditions. Oxygen radicals produced by chondrocytes is an important mechanism by which chondrocytes induce matrix degradation. In the present study, we extend these observations by studying oxidative processes against osteoblasts. Osteoblasts were mixed in in vitro culture with 200 microM menadione. The cytotoxic effect of menadione-induced oxidative stress was monitored by lucigenin- or luminol-amplified chemiluminescence, tetrazolium assay and immunocytochemical study. Results showed that adding menadione induces an oxidative stress on osteoblasts, via superoxide and hydrogen peroxide production, that can be eradicated by superoxide dismutase (SOD) and catalase in a dose-dependent manner. Catalase and the appropriate concentration of dimethyl sulfoxide have a protective effect on cytotoxicity induced by menadione, whereas SOD does not. Menadione-treated osteoblasts have a strong affinity for annexin V, and the nuclei are strongly stained by TUNEL (TdT-mediated dUTP nick-end labelling). The results suggest that menadione-triggered production of reactive oxygen species leads to apoptosis of osteoblasts. PMID:9447250

Sun, J S; Tsuang, Y H; Huang, W C; Chen, L T; Hang, Y S; Lu, F J

1997-12-01

42

Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells.  

PubMed

Published toxicology data on chitosan nanoparticles (NP) often lack direct correlation to the in situ size and surface characteristics of the nanoparticles, and the repeated NP assaults as experienced in chronic use. The aim of this paper was to breach these gaps. Chitosan nanoparticles synthesized by spinning disc processing were characterised for size and zeta potential in HBSS and EMEM at pHs 6.0 and 7.4. Cytotoxicity against the Caco-2 cells was evaluated by measuring the changes in intracellular mitochondrial dehydrogenase activity, TEER and sodium fluorescein transport data and cell morphology. Cellular uptake of NP was observed under the confocal microscope. Contrary to established norms, the collective data suggest that the in vitro cytotoxicity of NP against the Caco-2 cells was less influenced by positive surface charges than by the particle size. Particle size was in turn determined by the pH of the medium in which the NP was dispersed, with the mean size ranging from 25 to 333 nm. At exposure concentration of 0.1%, NP of 25 ± 7 nm (zeta potential 5.3 ± 2.8 mV) was internalised by the Caco-2 cells, and the particles were observed to inflict extensive damage to the intracellular organelles. Concurrently, the transport of materials along the paracellular pathway was significantly facilitated. The Caco-2 cells were, however, capable of recovering from such assaults 5 days following NP removal, although a repeat NP exposure was observed to produce similar effects to the 1st exposure, with the cells exhibiting comparable resiliency to the 2nd assault. PMID:22609640

Loh, Jing Wen; Saunders, Martin; Lim, Lee-Yong

2012-08-01

43

Cytotoxicity of peptide-coated silver nanoparticles on the human intestinal cell line Caco-2.  

PubMed

Silver nanoparticles are used in a wide range of consumer products such as clothing, cosmetics, household goods, articles of daily use and pesticides. Moreover, the use of a nanoscaled silver hydrosol has been requested in the European Union for even nutritional purposes. However, despite the wide applications of silver nanoparticles, there is a lack of information concerning their impact on human health. In order to investigate the effects of silver nanoparticles on human intestinal cells, we used the Caco-2 cell line and peptide-coated silver nanoparticles with defined colloidal, structural and interfacial properties. The particles display core diameter of 20 and 40 nm and were coated with the small peptide L-cysteine L-lysine L-lysine. Cell viability and proliferation were measured using Promegas CellTiter-Blue® Cell Viability assay, DAPI staining and impedance measurements. Apoptosis was determined by Annexin-V/7AAD staining and FACS analysis, membrane damage with Promegas LDH assay and reactive oxygen species by dichlorofluorescein assay. Exposure of proliferating Caco-2 cells to silver nanoparticle induced decreasing adherence capacity and cytotoxicity, whereby the formation of reactive oxygen species could be the mode of action. The effects were dependent on particle size (20, 40 nm), doses (5-100 ?g/mL) and time of incubation (4-48 h). Apoptosis or membrane damage was not detected. PMID:22418598

Böhmert, Linda; Niemann, Birgit; Thünemann, Andreas F; Lampen, Alfonso

2012-07-01

44

Relation between the Redox State of Iron-Based Nanoparticles and Their Cytotoxicity toward Escherichia coli  

SciTech Connect

Iron-based nanoparticles have been proposed for an increasing number of biomedical or environmental applications although in vitro toxicity has been observed. The aim of this study was to understand the relationship between the redox state of iron-based nanoparticles and their cytotoxicity toward a Gram-negative bacterium, Escherichia coli. While chemically stable nanoparticles ({gamma}Fe2O3) have no apparent cytotoxicity, nanoparticles containing ferrous and, particularly, zerovalent iron are cytotoxic. The cytotoxic effects appear to be associated principally with an oxidative stress as demonstrated using a mutant strain of E. coli completely devoid of superoxide dismutase activity. This stress can result from the generation of reactive oxygen species with the interplay of oxygen with reduced iron species (FeII and/or Fe0) or from the disturbance of the electronic and/or ionic transport chains due to the strong affinity of the nanoparticles for the cell membrane.

Auffan,M.; Achouak, W.; Rose, J.; Roncato, M.; Chaneac, C.; Waite, D.; Miasion, A.; Woicik, J.; Wiesner, M.; Bottero, J.

2008-01-01

45

Silica-encapsulated magnetic nanoparticles: enzyme immobilization and cytotoxic study.  

PubMed

Silica-encapsulated magnetic nanoparticles (MNPs) were prepared via microemulsion method. The products were characterized by high resolution transmission electron microscopy (HRTEM) and energy-dispersive X-ray spectrum (EDS). MNPs with no observed cytotoxic activity against human lung carcinoma cell and brine shrimp lethality were used as suitable support for glucose oxidase (GOD) immobilization. Binding of GOD onto the support was confirmed by the FTIR spectra. The amount of immobilized GODs was 95 mg/g. Storage stability study showed that the immobilized GOD retained 98% of its initial activity after 45 days and 90% of the activity was also remained after 12 repeated uses. Considerable enhancements in thermal stabilities were observed for the immobilized GOD at elevated temperatures up to 80°C and the activity of immobilized enzyme was less sensitive to pH changes in solution. PMID:22269345

Ashtari, Khadijeh; Khajeh, Khosro; Fasihi, Javad; Ashtari, Parviz; Ramazani, Ali; Vali, Hojatollah

2012-05-01

46

Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects  

PubMed Central

Background The purpose of this study was to investigate the mechanism of noxious effects of amorphous silica nanoparticles on human endothelial cells. Methods Nanoparticle uptake was examined by transmission electron microscopy. Electrochemical nanosensors were used to measure the nitric oxide (NO) and peroxynitrite (ONOO?) released by a single cell upon nanoparticle stimulation. The downstream inflammatory effects were measured by an enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and flow cytometry, and cytotoxicity was measured by lactate dehydrogenase assay. Results We found that the silica nanoparticles penetrated the plasma membrane and rapidly stimulated release of cytoprotective NO and, to a greater extent, production of cytotoxic ONOO?. The low [NO]/[ONOO?] ratio indicated increased nitroxidative/oxidative stress and correlated closely with endothelial inflammation and necrosis. This imbalance was associated with nuclear factor ?B activation, upregulation of key inflammatory factors, and cell death. These effects were observed in a nanoparticle size-dependent and concentration-dependent manner. Conclusion The [NO]/[ONOO?] imbalance induced by amorphous silica nanoparticles indicates a potentially deleterious effect of silica nanoparticles on vascular endothelium. PMID:22131828

Corbalan, J Jose; Medina, Carlos; Jacoby, Adam; Malinski, Tadeusz; Radomski, Marek W

2011-01-01

47

Interaction of citrate-coated silver nanoparticles with earthworm coelomic fluid and related cytotoxicity in Eisenia andrei.  

PubMed

Understanding the interaction of nanoparticles with biological fluid is important for predicting the behavior and toxicity of nanoparticles in living systems. The earthworm Eisenia andrei was exposed to citrate-coated silver nanoparticles (cAgNPs), and the interaction of cAgNPs with earthworm coelomic fluid (ECF), the cytotoxicity of cAgNPs in earthworm coelomocytes was assessed. The neutral red retention assay showed a reduction in lysosomal stability after exposure. The toxicity of silver ions dissolved from cAgNPs in the soil medium was not significant. The aggregation and dissolution of cAgNPs increased in ECF, which contains various electrolytes that alter the properties of nanoparticles, and their subsequent toxicity. Microscopic and dissolution studies demonstrated that the aggregation of cAgNPs rapidly increased, and readily dissolved in ECF. The bioavailability of cAgNPs to earthworms induced lysosomal cytotoxicity. This is the first report to test the interaction and lysosomal cytotoxicity of nanoparticles in earthworm biofluids. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24532537

Kwak, Jin Il; Lee, Woo-Mi; Kim, Shin Woong; An, Youn-Joo

2014-11-01

48

Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells.  

PubMed

Serious concerns have been expressed about potential risks of engineered nanoparticles. Regulatory health risk assessment of such particles has become mandatory for the safe use of nanomaterials in consumer products and medicines; including the potential effects on reproduction and fertility, are relevant for this risk evaluation. In this study, we examined effects of silver particles of nano- (20nm) and submicron- (200nm) size, and titanium dioxide nanoparticles (TiO(2)-NPs; 21nm), with emphasis on reproductive cellular- and genotoxicity. Ntera2 (NT2, human testicular embryonic carcinoma cell line), and primary testicular cells from C57BL6 mice of wild type (WT) and 8-oxoguanine DNA glycosylase knock-out (KO, mOgg1(-/-)) genotype were exposed to the particles. The latter mimics the repair status of human testicular cells vs oxidative damage and is thus a suitable model for human male reproductive toxicity studies. The results suggest that silver nano- and submicron-particles (AgNPs) are more cytotoxic and cytostatic compared to TiO(2)-NPs, causing apoptosis, necrosis and decreased proliferation in a concentration- and time-dependent manner. The 200nm AgNPs in particular appeared to cause a concentration-dependent increase in DNA-strand breaks in NT2 cells, whereas the latter response did not seem to occur with respect to oxidative purine base damage analysed with any of the particles tested. PMID:22085606

Asare, Nana; Instanes, Christine; Sandberg, Wiggo J; Refsnes, Magne; Schwarze, Per; Kruszewski, Marcin; Brunborg, Gunnar

2012-01-27

49

Hormesis effects of silver nanoparticles at non-cytotoxic doses to human hepatoma cells.  

PubMed

Silver nanoparticles (AgNPs) have attracted considerable attentions due to their unique properties and diverse applications. Although it has been reported that AgNPs have acute toxic effects on a variety of cultured mammalian cells and animal models, few studies have been conducted to evaluate the associated risk of AgNPs to human health at non-cytotoxic doses. In this paper, HepG2 cells were exposed to 10 nm and 100 nm AgNPs under non-cytotoxic conditions, and cell viability was assessed. At low doses, AgNPs displayed "hormesis" effects by accelerating cell proliferation. Further studies indicated that the activation states of MAPKs were differentially regulated in this process. Specifically, by increasing the expression of downstream genes, p38 MAPK played a central role in non-cytotoxic AgNP-induced hormesis. Moreover, the treatment of HepG2 cells with silver ions (Ag+) at the same dose levels induced distinct biological effects, suggesting that different intrinsic properties exist for AgNPs and Ag+. PMID:25033410

Jiao, Zhi-Hao; Li, Ming; Feng, Yi-Xing; Shi, Jia-Chen; Zhang, Jing; Shao, Bing

2014-01-01

50

Cytotoxicity evaluation of silica nanoparticles using fish cell lines.  

PubMed

Nanoparticles (NPs) have extensive industrial, biotechnological, and biomedical/pharmaceutical applications, leading to concerns over health risks to humans and biota. Among various types of nanoparticles, silica nanoparticles (SiO2 NPs) have become popular as nanostructuring, drug delivery, and optical imaging agents. SiO2 NPs are highly stable and could bioaccumulate in the environment. Although toxicity studies of SiO2 NPs to human and mammalian cells have been reported, their effects on aquatic biota, especially fish, have not been significantly studied. Twelve adherent fish cell lines derived from six species (rainbow trout, fathead minnow, zebrafish, goldfish, haddock, and American eel) were used to comparatively evaluate viability of cells by measuring metabolic impairment using Alamar Blue. Toxicity of SiO2 NPs appeared to be size-, time-, temperature-, and dose-dependent as well as tissue-specific. However, dosages greater than 100 ?g/mL were needed to achieve 24 h EC50 values (effective concentrations needed to reduce cell viability by 50%). Smaller SiO2 NPs (16 nm) were relatively more toxic than larger sized ones (24 and 44 nm) and external lining epithelial tissue (skin, gills)-derived cells were more sensitive than cells derived from internal tissues (liver, brain, intestine, gonads) or embryos. Higher EC50 values were achieved when toxicity assessment was performed at higher incubation temperatures. These findings are in overall agreement with similar human and mouse cell studies reported to date. Thus, fish cell lines could be valuable for screening emerging contaminants in aquatic environments including NPs through rapid high-throughput cytotoxicity bioassays. PMID:24357037

Vo, Nguyen T K; Bufalino, Mary R; Hartlen, Kurtis D; Kitaev, Vladimir; Lee, Lucy E J

2014-05-01

51

Drug delivery by polymeric nanoparticles induces autophagy in macrophages.  

PubMed

Drug delivery nanosystems are currently used in human therapy. In preliminary studies we have observed that Eudragit RS nanoparticles, prepared by nanoprecipitation or double emulsion techniques, are cytotoxic for NR8383 rat macrophages. In this study, we expand our previous analysis and suggest that unloaded Eudragit RS nanoparticles prepared by nanoprecipitation (NP/ERS) may induce important morphological and biochemical cellular modifications leading to cellular death. In NR8383 rat macrophages cell line exposed to doses varying from 15 to 100 ?g/mL, NP/ERS nanoparticles are internalized inside the cells, reach the mitochondria and alter the structure of these organelles. In addition, the exposure to nanoparticles induces cellular autophagy as demonstrated by electron microscopy analysis, microchip array, qRT-PCR and Western blot assays. Although toxicity of nanoparticles has already been evidenced, it is the first time that results show clearly that the toxicity of polymeric nanovectors may be related to an activation of autophagy. PMID:22119964

Eidi, H; Joubert, O; Némos, C; Grandemange, S; Mograbi, B; Foliguet, B; Tournebize, J; Maincent, P; Le Faou, A; Aboukhamis, I; Rihn, B H

2012-01-17

52

Cytotoxicity and apoptotic effects of tea polyphenol-loaded chitosan nanoparticles on human hepatoma HepG2 cells.  

PubMed

Tea polyphenols have strong antioxidant and antitumor activities. However, these health benefits are limited due to their poor in vivo stability and low bioavailability. Chitosan nanoparticles as delivery systems may provide an alternative approach for enhancing bioavailability of poorly absorbed drugs. In this study, tea polyphenol-loaded chitosan nanoparticles have been prepared using two different chitosan biomaterials, and their antitumor effects were evaluated in HepG2 cells, including cell cytotoxicity comparison, cell morphology analysis, cell apoptosis and cell cycle detection. The results indicated that the tea polyphenol-loaded chitosan nanoparticles showed a branch shape and heterogeneous distribution in prepared suspension. MTT assay suggested that tea polyphenol-loaded chitosan nanoparticles could inhibit the proliferation of HepG2 cells, and the cytotoxicity rates were increased gradually and appeared an obvious dose-dependent relationship. Transmission electron microscope images showed that the HepG2 cells treated with tea polyphenol-loaded chitosan nanoparticles exhibited some typical apoptotic features, such as microvilli disappearance, margination of nuclear chromatin, intracytoplasmic vacuoles and the mitochondrial swelling. In addition, the tea polyphenol-loaded chitosan nanoparticles had relatively weak inhibitory effects on HepG2 cancer cells compared with tea polyphenols. Tea polyphenols not only induced cancer cell apoptosis, but also promoted their necrosis. However, tea polyphenol-loaded chitosan nanoparticles exhibited their antitumor effects mainly through inducing cell apoptosis. Our results revealed that the inhibition effects of tea polyphenol-loaded chitosan nanoparticles on tumor cells probably depended on their controlled drug release and effective cell delivery. The chitosan nanoparticles themselves as the delivery carrier showed limited antitumor effects compared with their encapsulated drugs. PMID:24433880

Liang, Jin; Li, Feng; Fang, Yong; Yang, Wenjian; An, Xinxin; Zhao, Liyan; Xin, Zhihong; Cao, Lin; Hu, Qiuhui

2014-03-01

53

Thio-glucose bound gold nanoparticles enhance radio-cytotoxic targeting of ovarian cancer.  

PubMed

The treatment of ovarian cancer has traditionally been intractable, and required novel approaches to improve therapeutic efficiency. This paper reports that thio-glucose bound gold nanoparticles (Glu-GNPs) can be used as a sensitizer to enhance ovarian cancer radiotherapy. The human ovarian cancer cells, SK-OV-3, were treated by gold nanoparticles (GNPs) alone, irradiation alone, or GNPs in addition to irradiation. Cell uptake was assayed using inductively coupled plasma atomic emission spectroscopy (ICP-AES), while cytotoxicity induced by radiotherapy was measured using both 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide and clonogenic assays. The presence of reactive oxygen species (ROS) was determined using CM-H2-DCFDA confocal microscopy and cell apoptosis was determined by an Annexin V-FITC/propidium iodide (PI) kit with flow cytometry. The cells treated by Glu-GNPs resulted in an approximate 31% increase in nanoparticle uptake compared to naked GNPs (p < 0.005). Compared to the irradiation alone treatment, the intracellular uptake of Glu-GNPs resulted in increased inhibition of cell proliferation by 30.48% for 90 kVp and 26.88% for 6 MV irradiation. The interaction of x-ray radiation with GNPs induced elevated levels of ROS production, which is one of the mechanisms by which GNPs can enhance radiotherapy on ovarian cancer. PMID:21654036

Geng, Feng; Song, Kun; Xing, James Z; Yuan, Cunzhong; Yan, Shi; Yang, Qifeng; Chen, Jie; Kong, Beihua

2011-07-15

54

Thio-glucose bound gold nanoparticles enhance radio-cytotoxic targeting of ovarian cancer  

NASA Astrophysics Data System (ADS)

The treatment of ovarian cancer has traditionally been intractable, and required novel approaches to improve therapeutic efficiency. This paper reports that thio-glucose bound gold nanoparticles (Glu-GNPs) can be used as a sensitizer to enhance ovarian cancer radiotherapy. The human ovarian cancer cells, SK-OV-3, were treated by gold nanoparticles (GNPs) alone, irradiation alone, or GNPs in addition to irradiation. Cell uptake was assayed using inductively coupled plasma atomic emission spectroscopy (ICP-AES), while cytotoxicity induced by radiotherapy was measured using both 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide and clonogenic assays. The presence of reactive oxygen species (ROS) was determined using CM-H2-DCFDA confocal microscopy and cell apoptosis was determined by an Annexin V-FITC/propidium iodide (PI) kit with flow cytometry. The cells treated by Glu-GNPs resulted in an approximate 31% increase in nanoparticle uptake compared to naked GNPs (p < 0.005). Compared to the irradiation alone treatment, the intracellular uptake of Glu-GNPs resulted in increased inhibition of cell proliferation by 30.48% for 90 kVp and 26.88% for 6 MV irradiation. The interaction of x-ray radiation with GNPs induced elevated levels of ROS production, which is one of the mechanisms by which GNPs can enhance radiotherapy on ovarian cancer.

Geng, Feng; Song, Kun; Xing, James Z.; Yuan, Cunzhong; Yan, Shi; Yang, Qifeng; Chen, Jie; Kong, Beihua

2011-07-01

55

Cytotoxic, genotoxic and the hemolytic effect of titanium dioxide (TiO2 ) nanoparticles on human erythrocyte and lymphocyte cells in vitro.  

PubMed

With the increasing clinical use of titanium dioxide (TiO2 ) nanoparticles, a better understanding of their safety in the blood stream is required. The present study evaluates the toxic effect of commercially available TiO2 nanoparticles (~100 nm) using a battery of cytotoxic, genotoxic, hemolytic and morphological parameters. The cytotoxic effects of TiO2 nanoparticles in human lymphocyte cells were studied with respect to membrane damage, mitochondrial function, metabolic activity and lysosomal membrane stability. Genotoxicity in lymphocyte cells was quantitated using a comet assay. The mode of cell death (apoptosis/necrosis) was evaluated using PI/Annexin V staining. TiO2 nanoparticles were also evaluated for their hemolytic properties, osmotic fragility and interaction with hemoglobin. Human erythrocyte cells were studied for morphological alterations using atomic force microscopy (AFM). Results suggest that the particles could induce a significant reduction in mitochondrial dehydrogenase activity in human lymphocyte cells. Membrane integrity remained unaffected by nanoparticle treatment. DNA damage and apoptosis were induced by TiO2 nanoparticles in a dose-dependent manner. A study on human erythrocyte cells revealed a hemolytic property of TiO2 nanoparticles characterized by spherocytosis and echinocytosis. Spectral analysis revealed a hemoglobin TiO2 nanoparticle interaction. Our in vitro study results suggest that commercially available blood contacting nanoparticles (TiO2 nanoparticle) should be carefully evaluated for their toxic potential. PMID:23616399

Ghosh, Manosij; Chakraborty, Anirban; Mukherjee, Anita

2013-10-01

56

Pyridoxine mitigates cadmium induced hepatic cytotoxicity and oxidative stress  

Microsoft Academic Search

Therapeutic potential of pyridoxine (vit B6) was evaluated against cadmium induced hepatic cytotoxicity in culture and oxidative stress in rats. Nonmalignant “Chang” liver cell culture was exposed to Cd (cadmium chloride) that produced cytotoxicity in terms of increase in cell growth inhibition rate, alanine aminotransferase, lactate dehydrogenase and lipid peroxidation, which was significantly mitigated by pyridoxine in a concentration dependent

Yi-Fei Wen; Jun-Quan Zhao; Monika Bhadauria; Satendra Kumar Nirala

2010-01-01

57

On-Chip Evaluation of Shear Stress Effect on Cytotoxicity of Mesoporous Silica Nanoparticles  

PubMed Central

In this work, nanotoxicity in the bloodstream was modeled and the cytotoxicity of sub-50 nm mesoporous silica nanoparticles to human endothelial cells was investigated under microfluidic flow conditions. Compared to traditional in vitro cytotoxicity assays performed under static conditions, unmodified mesoporous silica nanoparticles show higher and shear stress-dependent toxicity to endothelial cells under flow conditions. Interestingly, even under flow conditions, highly organo-modified mesoporous silica nanoparticles show no significant toxicity to endothelial cells. This paper clearly demonstrates that shear stress is an important factor to be considered in in vitro nanotoxicology assessments and provides a simple device for pursuing this consideration. PMID:22032307

Kim, Donghyuk; Lin, Yu-Shen; Haynes, Christy L.

2011-01-01

58

The effect of poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity  

Microsoft Academic Search

The aim of this work was to investigate the effect of triblock copolymer poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity. Docetaxel-loaded nanoparticles were prepared by oil-in-water emulsion\\/solvent evaporation technique using biodegradable poly(lactic-co-glycolic acid) (PLGA) with or without addition of poloxamer 188, respectively. The resulting nanoparticles were found to be spherical with a rough and porous surface.

Fei Yan; Chao Zhang; Yi Zheng; Lin Mei; Lina Tang; Cunxian Song; Hongfan Sun; Laiqiang Huang

2010-01-01

59

Nanoparticles Induced Microscaled Pore Formation on Supported Lipid Bilayer  

NASA Astrophysics Data System (ADS)

Most of recent researches on the cytotoxicity of nanomaterials focused on hydrophilic nanomaterials because of their good dispersion in water, but much less on hydrophobic ones. In this work, we have investigated the effect of semi-hydrophobic nanoparticles (NPs) on the dynamics and morphology of model cell membrane. We have found carboxyl functionalized polystyrene nanoparticles can induce the formation of microscaled pores on neutral supported Egg PC lipid bilayer at the ionic strength range similar to that in the human body with a strong dependence on nanoparticle size and concentration. The hydrophobic interaction between the NP surface and lipid bilayer is accounted for the induced line tension in lipid bilayer; when the tension exceeds a critical value, pores are formed and grow rapidly with dependence on nanoparticle size and ionic strength.

Jing, Benxin; Zhu, Y. Elaine

2011-03-01

60

Effect of Polyethylene Glycol Modification of TiO2 Nanoparticles on Cytotoxicity and Gene Expressions in Human Cell Lines  

PubMed Central

Nanoparticles (NPs) are tiny materials used in a wide range of industrial and medical applications. Titanium dioxide (TiO2) is a type of nanoparticle that is widely used in paints, pigments, and cosmetics; however, little is known about the impact of TiO2 on human health and the environment. Therefore, considerable research has focused on characterizing the potential toxicity of nanoparticles such as TiO2 and on understanding the mechanism of TiO2 NP-induced nanotoxicity through the evaluation of biomarkers. Uncoated TiO2 NPs tend to aggregate in aqueous media, and these aggregates decrease cell viability and induce expression of stress-related genes, such as those encoding interleukin-6 (IL-6) and heat shock protein 70B’ (HSP70B’), indicating that TiO2 NPs induce inflammatory and heat shock responses. In order to reduce their toxicity, we conjugated TiO2 NPs with polyethylene glycol (PEG) to eliminate aggregation. Our findings indicate that modifying TiO2 NPs with PEG reduces their cytotoxicity and reduces the induction of stress-related genes. Our results also suggest that TiO2 NP-induced effects on cytotoxicity and gene expression vary depending upon the cell type and surface modification. PMID:22489177

Mano, Sharmy Saimon; Kanehira, Koki; Sonezaki, Shuji; Taniguchi, Akiyoshi

2012-01-01

61

The noncellular reduction of MTT tetrazolium salt by TiO? nanoparticles and its implications for cytotoxicity assays.  

PubMed

We report results of noncellular tests, revealing the occurrence of photocatalytic interactions between titanium dioxide (TiO2, titania) nanoparticles and the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide] cytotoxicity indicator. These interactions induce the reduction of MTT and formation of purple formazan under biologically relevant conditions. Classical MTT assays have been performed to evaluate the production of formazan in DMEM-F12 and RPMI-1640 cell culture media (containing 10% fetal bovine serum-FBS) treated with Degussa-P25 TiO2 nanoparticles, in the absence of cells. The colorimetric determinations revealed the noncellular MTT to formazan transformation induced by TiO2 nanoparticles, under conditions commonly used for in vitro cytotoxicity testing of nanomaterials. The formazan precipitation was found to be proportional to the TiO2 concentration, being enhanced under laboratory daylight exposure. The photocatalytic nature of the studied effect was assessed under UV irradiation at 365nm. The biological significance of the reported reaction was established with respect to cellular reference experiments performed on V79-4, HeLa and B16 cell lines. The results show false viability increases with up to 14% (for TiO2 concentrations generally higher than 50?g/ml), induced by the TiO2-MTT reaction. This type of artifacts may lead to underestimated toxicity or false proliferation results. PMID:23531555

Lupu, A R; Popescu, T

2013-08-01

62

Cytotoxicity of Paclitaxel Incorporated in PLGA Nanoparticles on Hypoxic Human Tumor Cells  

Microsoft Academic Search

Purpose  The aim of this work was to prepare paclitaxel-loaded PLGA nanoparticles and determine cytotoxicity of released paclitaxel\\u000a for two hypoxic human tumor cell lines: breast carcinoma (MCF-7) and carcinoma cervicis (HeLa).\\u000a \\u000a \\u000a \\u000a Methods  Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel were prepared by o\\/w emulsification-solvent evaporation\\u000a method. Physicochemical characteristics of nanoparticles were studied. Cellular uptake of nanoparticles was evaluated by transmission\\u000a electronic microscopy and

Cheng Jin; Ling Bai; Hong Wu; Wenjie Song; Guozhen Guo; Kefeng Dou

2009-01-01

63

Assessment of cytotoxicity of quantum dots and gold nanoparticles using cell-based impedance spectroscopy.  

PubMed

A continuous online technique based on electric cell-substrate impedance sensing (ECIS) was demonstrated for measuring the concentration and time response function of fibroblastic V79 cells exposed to nanomaterials such as quantum dots (QDs) and fluorescent gold nanoparticles. The half-inhibition concentration, (ECIS50), the required concentration to attain 50% inhibition of the cytotoxic response, was estimated from the response function to ascertain cytotoxicity during the course of measurement. The ECIS50 values agreed well with the results obtained using the standard neutral red assay. Cadmium selenide quantum dots showed direct cytotoxicity with the ECIS assay. For the cadmium telluride quantum dots, significant toxicity could be assigned to free cadmium, although additional toxicity could be attributed to the QDs per se. The QDs synthesized with indium gallium phosphide and the fluorescent gold nanoparticles were not cytotoxic. PMID:18553941

Male, Keith B; Lachance, Bernard; Hrapovic, Sabahudin; Sunahara, Geoff; Luong, John H T

2008-07-15

64

Evaluation of the cytotoxic and inflammatory potential of differentially shaped zinc oxide nanoparticles  

Microsoft Academic Search

Zinc oxide (ZnO) nanoparticles have wide-ranging applications in a diverse array of industrial and consumer products, from\\u000a ceramic manufacture and paint formulation to sunscreens and haircare products. Hence, it is imperative to rigorously characterize\\u000a the health and safety aspects of human exposure to ZnO nanoparticles. This study therefore evaluated the cellular association,\\u000a cytotoxic and inflammatory potential of spherical and sheet-shaped

Boon Chin Heng; Xinxin Zhao; Eng Chok Tan; Nurulain Khamis; Aarti Assodani; Sijing Xiong; Christiane Ruedl; Kee Woei Ng; Joachim Say-Chye Loo

65

Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells.  

PubMed

The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P < 0.05). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma. PMID:24868467

Mohammadi Ghalaei, Parviz; Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

2014-01-01

66

Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells  

PubMed Central

The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P < 0.05). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma. PMID:24868467

Varshosaz, Jaleh; Sadeghi Aliabadi, Hojatollah

2014-01-01

67

Evaluation of antioxidant, antibacterial and cytotoxic effects of green synthesized silver nanoparticles by Piper longum fruit.  

PubMed

Silver nanoparticles synthesized through bio-green method has been reported to have biomedical applications to control pathogenic microbes as it is cost effective compared to commonly used physical and chemical methods. In present study, silver nanoparticles were synthesized using aqueous Piper longum fruit extract (PLFE) and confirmed by UV-visible spectroscopy. The nanoparticles were spherical in shape with an average particle size of 46nm as determined by scanning electronic microscopy (SEM) and dynamic light scattering (DLS) particle size analyzer respectively. FT-IR spectrum revealed the capping of the phytoconstituents, probably polyphenols from P. longum fruit extract and stabilizing the nanoparticles. Further the ferric ion reducing test, confirmed that the capping agents were condensed tannins. The aqueous P. longum fruit extract (PLFE) and the green synthesized silver nanoparticles (PLAgNPs) showed powerful antioxidant properties in in vitro antioxidant assays. The results from the antimicrobial assays suggested that green synthesized silver nanoparticles (PLAgNPs) were more potent against pathogenic bacteria than the P. longum fruit extract (PLFE) alone. The nanoparticles also showed potent cytotoxic effect against MCF-7 breast cancer cell lines with an IC 50 value of 67?g/ml/24h by the MTT assay. These results support the advantages of using bio-green method for synthesizing silver nanoparticles with antioxidant, antimicrobial and cytotoxic activities those are simple and cost effective as well. PMID:24268240

Reddy, N Jayachandra; Nagoor Vali, D; Rani, M; Rani, S Sudha

2014-01-01

68

Cytotoxic effects of gold nanoparticles: a multiparametric study.  

PubMed

The in vitro labeling of therapeutic cells with nanoparticles (NPs) is becoming more and more common, but concerns about the possible effects of the NPs on the cultured cells are also increasing. In the present work, we evaluate the effects of poly(methacrylic acid)-coated 4 nm diameter Au NPs on a variety of sensitive and therapeutically interesting cell types (C17.2 neural progenitor cells, human umbilical vein endothelial cells, and PC12 rat pheochromocytoma cells) using a multiparametric approach. Using various NP concentrations and incubation times, we performed a stepwise analysis of the NP effects on cell viability, reactive oxygen species, cell morphology, cytoskeleton architecture, and cell functionality. The data show that higher NP concentrations (200 nM) reduce cell viability mostly through induction of reactive oxygen species, which was significantly induced at concentrations of 50 nM Au NPs or higher. At these concentrations, both actin and tubulin cytoskeleton were deformed and resulted in reduced cell proliferation and cellular differentiation. In terms of cell functionality, the NPs significantly impeded neurite outgrowth of PC12 cells up to 20 nM concentrations. At 10 nM, no significant effects on any cellular parameter could be observed. These data highlight the importance of using multiple assays to cover the broad spectrum of cell-NP interactions and to determine safe NP concentrations and put forward the described protocol as a possible template for future cell-NP interaction studies under comparable and standardized conditions. PMID:22659047

Soenen, Stefaan J; Manshian, Bella; Montenegro, José Maria; Amin, Faheem; Meermann, Björn; Thiron, Toke; Cornelissen, Maria; Vanhaecke, Frank; Doak, Shareen; Parak, Wolfgang J; De Smedt, Stefaan; Braeckmans, Kevin

2012-07-24

69

Oxidative stress mediated cytotoxicity of biologically synthesized silver nanoparticles in human lung epithelial adenocarcinoma cell line  

NASA Astrophysics Data System (ADS)

The goal of the present study was to investigate the toxicity of biologically prepared small size of silver nanoparticles in human lung epithelial adenocarcinoma cells A549. Herein, we describe a facile method for the synthesis of silver nanoparticles by treating the supernatant from a culture of Escherichia coli with silver nitrate . The formation of silver nanoparticles was characterized using various analytical techniques. The results from UV-visible (UV-vis) spectroscopy and X-ray diffraction analysis show a characteristic strong resonance centered at 420 nm and a single crystalline nature, respectively. Fourier transform infrared spectroscopy confirmed the possible bio-molecules responsible for the reduction of silver from silver nitrate into nanoparticles. The particle size analyzer and transmission electron microscopy results suggest that silver nanoparticles are spherical in shape with an average diameter of 15 nm. The results derived from in vitro studies showed a concentration-dependent decrease in cell viability when A549 cells were exposed to silver nanoparticles. This decrease in cell viability corresponded to increased leakage of lactate dehydrogenase (LDH), increased intracellular reactive oxygen species generation (ROS), and decreased mitochondrial transmembrane potential (MTP). Furthermore, uptake and intracellular localization of silver nanoparticles were observed and were accompanied by accumulation of autophagosomes and autolysosomes in A549 cells. The results indicate that silver nanoparticles play a significant role in apoptosis. Interestingly, biologically synthesized silver nanoparticles showed more potent cytotoxicity at the concentrations tested compared to that shown by chemically synthesized silver nanoparticles. Therefore, our results demonstrated that human lung epithelial A549 cells could provide a valuable model to assess the cytotoxicity of silver nanoparticles.

Han, Jae Woong; Gurunathan, Sangiliyandi; Jeong, Jae-Kyo; Choi, Yun-Jung; Kwon, Deug-Nam; Park, Jin-Ki; Kim, Jin-Hoi

2014-09-01

70

Cytotoxic effects and the mechanism of three types of magnetic nanoparticles on human hepatoma BEL-7402 cells  

NASA Astrophysics Data System (ADS)

The evaluation of the toxicity of magnetic nanoparticles (MNPs) has attracted much attention in recent years. The current study aimed to investigate the cytotoxic effects of Fe3O4, oleic acid-coated Fe3O4 (OA-Fe3O4), and carbon-coated Fe (C-Fe) nanoparticles on human hepatoma BEL-7402 cells and the mechanisms. WST-1 assay demonstrated that the cytotoxicity of three types of MNPs was in a dose-dependent manner. G1 (Fe3O4 and OA-Fe3O4) phase and G2 (C-Fe) phase cell arrests and apoptosis induced by MNPs were detected by flow cytometry analysis. The increase in apoptosis was accompanied with the Bax over-expression, mitochondrial membrane potential decrease, and the release of cytochrome C from mitochondria into cytosol. Moreover, apoptosis was further confirmed by morphological and biochemical hallmarks, such as swollen mitochondria with lysing cristae and caspase-3 activation. Our results revealed that certain concentrations of the three types of MNPs affect BEL-7402 cells viability via cell arrest and inducing apoptosis, and the MNPs-induced apoptosis is mediated through the mitochondrial-dependent pathway. The influence potency of MNPs observed in all experiments would be: C-Fe > Fe3O4 > OA-Fe3O4.

Kai, Wei; Xiaojun, Xu; Ximing, Pu; Zhenqing, Hou; Qiqing, Zhang

2011-07-01

71

Cytotoxic effects and the mechanism of three types of magnetic nanoparticles on human hepatoma BEL-7402 cells  

PubMed Central

The evaluation of the toxicity of magnetic nanoparticles (MNPs) has attracted much attention in recent years. The current study aimed to investigate the cytotoxic effects of Fe3O4, oleic acid-coated Fe3O4 (OA-Fe3O4), and carbon-coated Fe (C-Fe) nanoparticles on human hepatoma BEL-7402 cells and the mechanisms. WST-1 assay demonstrated that the cytotoxicity of three types of MNPs was in a dose-dependent manner. G1 (Fe3O4 and OA-Fe3O4) phase and G2 (C-Fe) phase cell arrests and apoptosis induced by MNPs were detected by flow cytometry analysis. The increase in apoptosis was accompanied with the Bax over-expression, mitochondrial membrane potential decrease, and the release of cytochrome C from mitochondria into cytosol. Moreover, apoptosis was further confirmed by morphological and biochemical hallmarks, such as swollen mitochondria with lysing cristae and caspase-3 activation. Our results revealed that certain concentrations of the three types of MNPs affect BEL-7402 cells viability via cell arrest and inducing apoptosis, and the MNPs-induced apoptosis is mediated through the mitochondrial-dependent pathway. The influence potency of MNPs observed in all experiments would be: C-Fe > Fe3O4 > OA-Fe3O4. PMID:21801413

2011-01-01

72

Multiple cytotoxic and genotoxic effects induced in vitro by differently shaped copper oxide nanomaterials.  

PubMed

In nanotoxicology, the capacity of nanoparticles of the same composition but different shape to induce cytotoxicity and genotoxicity is largely unknown. A series of cytotoxic and genotoxic responses following in vitro exposure to differently shaped CuO nanoparticles (CuO NPs, mass concentrations from 0.1 to 100 ?g/ml) were assessed in murine macrophages RAW 264.7 and in peripheral whole blood from healthy volunteers. Cytotoxicity, cytostasis and genotoxicity were evaluated by the colorimetric assay of formazan reduction [3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT)] and by the cytokinesis-block micronucleus cytome (CBMN Cyt) assay. The comet assay was applied for detecting DNA strand breaks and information on oxidative damage to DNA (oxidised purines and pyrimidines). The MTT assay revealed a decrease in cell viability in RAW 264.7 cells and peripheral blood lymphocytes (PBL) with significant dose-effect relationships for the different CuO NP shapes. The comet assay revealed a dose-dependent increase in primary DNA damage, and a significant increase in oxidative damage to DNA was also detectable, as well as increased frequency of micronuclei in binucleated cells, often in a dose-related manner. Proliferative activity, cytotoxicity and apoptotic markers showed a significant trend in the two cell types. Finally, we have differentiated clastogenic events from aneugenic events by fluorescence in situ hybridisation with human and murine pancentromeric probes, revealing for the first time characteristic aneugenic responses related to the shape of CuO NPs and cell type. Independently of size and shape, all CuO NPs revealed a clear-cut cytotoxic and genotoxic potential; this suggests that CuO NPs are good candidates for positive controls in nanotoxicology. PMID:23462852

Di Bucchianico, Sebastiano; Fabbrizi, Maria Rita; Misra, Superb K; Valsami-Jones, Eugenia; Berhanu, Deborah; Reip, Paul; Bergamaschi, Enrico; Migliore, Lucia

2013-05-01

73

Fluorescent chitosan functionalized magnetic polymeric nanoparticles: Cytotoxicity and in vitro evaluation of cellular uptake.  

PubMed

Nanoparticles possessing magnetic and fluorescent properties were fabricated by the covalent attachment of fluorescein isothiocyanate onto magnetic polymeric nanoparticles functionalized by chitosan. The synthesized magnetic polymeric nanoparticles-chitosan/fluorescein isothiocyanate were successfully used for labeling the living organ and blood-related cancer cells, i.e., HeLa, Hep G2, and K562 cells. The cytotoxicity test of nanoparticles at various incubation times indicated the high cell viability (>90%) without morphological change. The confocal microscopy revealed that they could pass through cell membrane within 2?h for K562 cells and 3?h for HeLa and Hep G2 cells and then confine inside cytoplasm of all types of tested cells for at least 24?h. Therefore, the synthesized magnetic polymeric nanoparticles-chitosan/fluorescein isothiocyanate would potentially be used as cell tracking in theranostic applications. PMID:24951458

Kaewsaneha, Chariya; Jangpatarapongsa, Kulachart; Tangchaikeeree, Tienrat; Polpanich, Duangporn; Tangboriboonrat, Pramuan

2014-11-01

74

Heparin and Carboxymethylchitosan Metal Nanoparticles: An Evaluation of Their Cytotoxicity  

PubMed Central

In the search for noninvasive diagnostic techniques and new therapies, “nanosystems”, which are capable of binding and targeting bioactive molecules, are becoming increasingly important. In this context, biocompatible coatings are gaining interest, not only for their biological effects but also because they are considered capable to mask nanoparticle toxicity. In this work, we have compared the toxicity of nanoparticles coated with heparin and carboxymethylchitosan in the SKOV-3 cell line. Our results indicate that heparin and carboxymethylchitosan coatings do not guarantee the decrease of nanoparticle intrinsic toxicity which is often envisaged. Nonetheless, these coatings provide the opportunity for further functionalization with a variety of biomolecules for their use in theranostics. PMID:23509708

Bava, Adriana; Cappellini, Francesca; Pedretti, Elisa; Rossi, Federica; Caruso, Enrico; Vismara, Elena; Chiriva-Internati, Maurizio; Bernardini, Giovanni; Gornati, Rosalba

2013-01-01

75

Changing exposure media can reverse the cytotoxicity of ceria nanoparticles for Escherichia coli.  

PubMed

Ceria nanoparticles have attracted a great deal of concern about their impact on human health and the environment due to their widespread applications. In the present work, different exposure media (normal saline and phosphate-buffered saline [PBS]) were used to adjust the surface charge density in order to investigate the influence of surface charge on the cytotoxicity of ceria nanoparticles for Escherichia coli. The results showed that the direct contact mediated by the electrostatic attraction between the cell wall and the positive-charged ceria nanoparticles in normal saline would result in outer membrane destabilization, increased reactive oxygen species (ROS) production and loss of viability. The situation in PBS was totally different, with significantly reduced contacts, so no outer membrane destabilization, no increased ROS production, and no cytotoxicity. The results suggested that surface charge density was closely involved in the cytotoxicity of ceria nanoparticles for E. coli. This work as a well designed comparison study contributes to a better understanding of the charge-associated biological effects of nanomaterials. PMID:21486189

He, Xiao; Kuang, Yashu; Li, Yuanyuan; Zhang, Haifeng; Ma, Yuhui; Bai, Wei; Zhang, Zhiyong; Wu, Zhenqiang; Zhao, Yuliang; Chai, Zhifang

2012-05-01

76

Glyconanoparticle Aided Detection of ?-Amyloid by Magnetic Resonance Imaging and Attenuation of ?-Amyloid Induced Cytotoxicity  

PubMed Central

The development of a noninvasive method for the detection of Alzheimer’s disease is of high current interest, which can be critical in early diagnosis and in guiding treatment of the disease. The aggregates of ?-amyloid are a pathological hallmark of Alzheimer’s disease. Carbohydrates such as gangliosides have been shown to play significant roles in initiation of amyloid aggregation. Herein, we report a biomimetic approach using superparamagnetic iron oxide glyconanoparticles to detect ?-amyloid. The bindings of ?-amyloid by the glyconanoparticles were demonstrated through several techniques including enzyme linked immunosorbent assay, gel electrophoresis, tyrosine fluorescence assay, and transmission electron microscopy. The superparamagnetic nature of the nanoparticles allowed easy detection of ?-amyloid both in vitro and ex vivo by magnetic resonance imaging. Furthermore, the glyconanoparticles not only were nontoxic to SH-SY5Y neuroblastoma cells but also greatly reduced ?-amyloid induced cytotoxicity to cells, highlighting the potential of these nanoparticles for detection and imaging of ?-amyloid. PMID:23590250

2013-01-01

77

Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after intratracheal instillation in rats  

PubMed Central

Summary Silver nanoparticles (AgNP) are among the most promising nanomaterials, and their usage in medical applications and consumer products is growing rapidly. To evaluate possible adverse health effects, especially to the lungs, the current study focused on the cytotoxic and proinflammatory effects of AgNP after the intratracheal instillation in rats. Monodisperse, PVP-coated AgNP (70 nm) showing little agglomeration in aqueous suspension were instilled intratracheally. After 24 hours, the lungs were lavaged, and lactate dehydrogenase (LDH), total protein, and cytokine levels as well as total and differential cell counts were measured in the bronchoalveolar lavage fluid (BALF). Instillation of 50 µg PVP-AgNP did not result in elevated LDH, total protein, or cytokine levels in BALF compared to the control, whereas instillation of 250 µg PVP-AgNP caused a significant increase in LDH (1.9-fold) and total protein (1.3-fold) levels as well as in neutrophil numbers (60-fold) of BALF. Furthermore, while there was no change in BALF cytokine levels after the instillation of 50 µg PVP-AgNP, instillation of 250 µg PVP-AgNP resulted in significantly increased levels of seven out of eleven measured cytokines. These finding suggest that exposure to inhaled AgNP can induce moderate pulmonary toxicity, but only at rather high concentrations. PMID:24455451

Hirn, Stephanie; Wenk, Alexander; Diendorf, Jörg; Epple, Matthias; Johnston, Blair D; Krombach, Fritz; Kreyling, Wolfgang G; Schleh, Carsten

2013-01-01

78

Biosynthesis, Antimicrobial and Cytotoxic Effect of Silver Nanoparticles Using a Novel Nocardiopsis sp. MBRC-1  

PubMed Central

The biosynthesis of nanoparticles has been proposed as a cost effective environmental friendly alternative to chemical and physical methods. Microbial synthesis of nanoparticles is under exploration due to wide biomedical applications, research interest in nanotechnology and microbial biotechnology. In the present study, an ecofriendly process for the synthesis of nanoparticles using a novel Nocardiopsis sp. MBRC-1 has been attempted. We used culture supernatant of Nocardiopsis sp. MBRC-1 for the simple and cost effective green synthesis of silver nanoparticles. The reduction of silver ions occurred when silver nitrate solution was treated with the Nocardiopsis sp. MBRC-1 culture supernatant at room temperature. The nanoparticles were characterized by UV-visible, TEM, FE-SEM, EDX, FTIR, and XRD spectroscopy. The nanoparticles exhibited an absorption peak around 420?nm, a characteristic surface plasmon resonance band of silver nanoparticles. They were spherical in shape with an average particle size of 45 ± 0.15?nm. The EDX analysis showed the presence of elemental silver signal in the synthesized nanoparticles. The FTIR analysis revealed that the protein component in the form of enzyme nitrate reductase produced by the isolate in the culture supernatant may be responsible for reduction and as capping agents. The XRD spectrum showed the characteristic Bragg peaks of 1 2 3, 2 0 4, 0 4 3, 1 4 4, and 3 1 1 facets of the face centered cubic silver nanoparticles and confirms that these nanoparticles are crystalline in nature. The prepared silver nanoparticles exhibited strong antimicrobial activity against bacteria and fungi. Cytotoxicity of biosynthesized AgNPs against in vitro human cervical cancer cell line (HeLa) showed a dose-response activity. IC50 value was found to be 200??g/mL of AgNPs against HeLa cancer cells. Further studies are needed to elucidate the toxicity and the mechanism involved with antimicrobial and anticancer activity of the synthesized AgNPs as nanomedicine. PMID:23936787

Manivasagan, Panchanathan; Senthilkumar, Kalimuthu; Sivakumar, Kannan; Kim, Se-Kwon

2013-01-01

79

Reactive oxygen species mediated DNA damage in human lung alveolar epithelial (A549) cells from exposure to non-cytotoxic MFI-type zeolite nanoparticles.  

PubMed

Increasing utilization of engineered nanoparticles in the field of electronics and biomedical applications demands an assessment of risk associated with deliberate or accidental exposure. Metal based nanoparticles are potentially most important of all the nanoparticles in terms of health risks. Microporous alumino-silicates and pure silicates named as zeolites and zeo-type materials with variety of structures, chemical compositions, particle sizes and morphologies have a significant number of industrial uses such as in catalysis, sorption and ion-exchange processes. In particular, the nanosized particles due to their unique properties are used in hybrid organic-inorganic materials for photography, photonics, electronics, labeling, imaging, and sensing. The aim of the current study is to investigate pure silica MFI-type zeolites nanoparticles with sizes of 50nm and 100nm (samples MFI-50 and MFI-100) under suspended conditions and their toxicological effects on human lung alveolar (A549) cells under in vitro conditions. Live cell imaging showed that the nanoparticles precipitated from the colloidal suspension of cell culture media as large agglomerates, coming in contact with the cell surface through sedimentation. A cellular proliferative capacity test showed the zeolite nanoparticles to exhibit no significant cytotoxicity below a concentration of 100?g/ml. However, both the MFI-50 and MFI-100 nanoparticles induced high intracellular reactive oxygen species (ROS) generation and elevated mitochondrial membrane potential in the A549 cells over the measured time period of 12h and at concentrations up to ?50?g/ml. DNA fragmentation analysis using the comet assay showed that the MFI-50 and MFI-100 nanoparticles cause genotoxicity in a concentration dependent manner. Furthermore, the rate at which maximum genomic damage was caused by MFI-100 nanoparticles in the A549 cells was found to be high as compared to the MFI-50 nanoparticles. However, the damage caused by the MFI-50 nanoparticles was found to accumulate over a longer period of time as compared to MFI-100 nanoparticles. The study therefore points towards the capability of the non-cytotoxic zeolite nanoparticles to induce oxidative stress resulting in short-term altered cellular metabolism up-regulation and genomic instability. Although the damage was found to be short-lived, its persistence over longer durations, or stabilization cannot be neglected. Further studies are in progress to yield a better understanding of the mechanisms for oxidative stress and resulting cascade of events leading to genetic damage in the human lung alveolar epithelial cells following exposure to zeolite nanoparticles of different sizes. PMID:23103338

Bhattacharya, Kunal; Naha, Pratap C; Naydenova, Izabela; Mintova, Svetlana; Byrne, Hugh J

2012-12-17

80

Cytotoxicity induced by nanobacteria and nanohydroxyapatites in human choriocarcinoma cells  

PubMed Central

We explored the cytotoxic effects of nanobacteria (NB) and nanohydroxyapatites (nHAPs) against human choriocarcinoma cells (JAR) and the mechanisms of action underlying their cytotoxicity. JAR cells were co-cultured with NB and nHAPs for 48 h, and ultrastructural changes were more readily induced by NB than nHAPs. Autophagy in the plasma of JAR cells were observed in the NB group. The rate of apoptosis induced by NB was higher than that for nHAPs. The expression of Bax and FasR proteins in the NB group was stronger than that for the nHAP group. NB probably resulted in autophagic formation. Apoptosis was possibly activated via FasL binding to the FasR signaling pathway.

2014-01-01

81

Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells.  

PubMed

Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities, nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging, drug delivery and hyperthermia. Recent studies have shown that nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells. Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays. Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of reactive oxygen species (ROS) and depletion of antioxidant glutathione (GSH). Further, co-treatment with the antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to nickel ferrite nanoparticles, the level of mRNA expressions of cell cycle checkpoint protein p53 and apoptotic proteins (bax, caspase-3 and caspase-9) were significantly up-regulated, whereas the expression of anti-apoptotic proteins (survivin and bcl-2) were down-regulated. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways. PMID:21382431

Ahamed, Maqusood; Akhtar, Mohd Javed; Siddiqui, Maqsood A; Ahmad, Javed; Musarrat, Javed; Al-Khedhairy, Abdulaziz A; AlSalhi, Mohamad S; Alrokayan, Salman A

2011-05-10

82

Pyridoxine mitigates cadmium induced hepatic cytotoxicity and oxidative stress.  

PubMed

Therapeutic potential of pyridoxine (vit B6) was evaluated against cadmium induced hepatic cytotoxicity in culture and oxidative stress in rats. Nonmalignant "Chang" liver cell culture was exposed to Cd (cadmium chloride) that produced cytotoxicity in terms of increase in cell growth inhibition rate, alanine aminotransferase, lactate dehydrogenase and lipid peroxidation, which was significantly mitigated by pyridoxine in a concentration dependent manner. Acute exposure to Cd (6.5mg/kg body weight; ip once only) produced a condition of hepatic oxidative stress by substantially increasing lipid peroxidation and oxidized glutathione level along with corresponding decrease in reduced glutathione and various antioxidant enzymes, i.e., superoxide dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase. Cadmium administration significantly increased the leakage of liver marker enzymes in serum, i.e., transaminases, alkaline phosphatase and lactate dehydrogenase. Therapy with pyridoxine after 3h of Cd administration decreased the release of serum transaminases, alkaline phosphatase and lactate dehydrogenase towards control. Administration of pyridoxine inhibited lipid peroxidation and formation of oxidized glutathione, increased the reduced glutathione level and restored the activities of aforesaid antioxidant enzymes towards control. The observations clearly demonstrated that pyridoxine treatment mitigates cadmium induced hepatic cytotoxicity and oxidative stress and provides evidence that it may be used clinically against Cd-induced hepatic toxicity. PMID:21787648

Wen, Yi-Fei; Zhao, Jun-Quan; Bhadauria, Monika; Nirala, Satendra Kumar

2010-09-01

83

Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127  

PubMed Central

Magnetic nanoparticles are promising molecular imaging agents due to their relative high relaxivity and the potential to modify surface functionality to tailor biodistribution. In this work we describe the synthesis of magnetic nanoparticles using organic solvents with organometallic precursors. This method results in nanoparticles that are highly crystalline, and have uniform size and shape. The ability to create a monodispersion of particles of the same size and shape results in unique magnetic properties that can be useful for biomedical applications with MR imaging. Before these nanoparticles can be used in biological applications, however, means are needed to make the nanoparticles soluble in aqueous solutions and the toxicity of these nanoparticles needs to be studied. We have developed two methods to surface modify and transfer these nanoparticles to the aqueous phase using the biocompatible co-polymer, Pluronic F127. Cytotoxicity was found to be dependent on the coating procedure used. Nanoparticle effects on a cell-culture model was quantified using concurrent assaying; a LDH assay to determine cytotoxicity and an MTS assay to determine viability for a 24 hour incubation period. Concurrent assaying was done to insure that nanoparticles did not interfere with the colorimetric assay results. This report demonstrates that a monodispersion of nanoparticles of uniform size and shape can be manufactured. Initial cytotoxicity testing of new molecular imaging agents need to be carefully constructed to avoid interference and erroneous results. PMID:20623517

Gonzales, Marcela; Mitsumori, Lee M.; Kushleika, John V.; Rosenfeld, Michael E.; Krishnan, Kannan M.

2010-01-01

84

Cytotoxicity and cellular uptake of tri-block copolymer nanoparticles with different size and surface characteristics  

PubMed Central

Background Polymer nanoparticles (PNP) are becoming increasingly important in nanomedicine and food-based applications. Size and surface characteristics are often considered to be important factors in the cellular interactions of these PNP, although systematic investigations on the role of surface properties on cellular interactions and toxicity of PNP are scarce. Results Fluorescent, monodisperse tri-block copolymer nanoparticles with different sizes (45 and 90 nm) and surface charges (positive and negative) were synthesized, characterized and studied for uptake and cytotoxicity in NR8383 and Caco-2 cells. All types of PNP were taken up by the cells. The positive smaller PNP45 (45 nm) showed a higher cytotoxicity compared to the positive bigger PNP90 (90 nm) particles including reduction in mitochondrial membrane potential (??m), induction of reactive oxygen species (ROS) production, ATP depletion and TNF-? release. The negative PNP did not show any cytotoxic effect. Reduction in mitochondrial membrane potential (??m), uncoupling of the electron transfer chain in mitochondria and the resulting ATP depletion, induction of ROS and oxidative stress may all play a role in the possible mode of action for the cytotoxicity of these PNP. The role of receptor-mediated endocytosis in the intracellular uptake of different PNP was studied by confocal laser scanning microscopy (CLSM). Involvement of size and charge in the cellular uptake of PNP by clathrin (for positive PNP), caveolin (for negative PNP) and mannose receptors (for hydroxylated PNP) were found with smaller PNP45 showing stronger interactions with the receptors than bigger PNP90. Conclusions The size and surface characteristics of polymer nanoparticles (PNP; 45 and 90 nm with different surface charges) play a crucial role in cellular uptake. Specific interactions with cell membrane-bound receptors (clathrin, caveolin and mannose) leading to cellular internalization were observed to depend on size and surface properties of the different PNP. These properties of the nanoparticles also dominate their cytotoxicity, which was analyzed for many factors. The effective reduction in the mitochondrial membrane potential (??m), uncoupling of the electron transfer chain in mitochondria and resulting ATP depletion, induction of ROS and oxidative stress likely all play a role in the mechanisms behind the cytotoxicity of these PNP. PMID:22546147

2012-01-01

85

Cytotoxicity induced by grape seed proanthocyanidins: role of nitric oxide.  

PubMed

Grape seed proanthocyanidin extract (GPSE) at high doses has been shown to exhibit cytotoxicity that is associated with increased apoptotic cell death. Nitric oxide (NO), being a regulator of apoptosis, can be increased in production by the administration of GSPE. In a chick cardiomyocyte study, we demonstrated that high-dose (500 microg/ml) GSPE produces a significantly high level of NO that contributes to increased apoptotic cell death detected by propidium iodide and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. It is also associated with the depletion of intracellular glutathione (GSH), probably due to increased consumption by NO with the formation of S-nitrosoglutathione. Co-treatment with L-NAME, a NO synthase inhibitor, results in reduction of NO and apoptotic cell death. The decline in reduced GSH/oxidized GSH (GSSG) ratio is also reversed. N-Acetylcysteine, a thiol compound that reacts directly with NO, can reduce the increased NO generation and reverse the decreased GSH/GSSG ratio, thereby attenuating the cytotoxicity induced by high-dose GSPE. Taken together, these results suggest that endogenous NO synthase (NOS) activation and excessive NO production play a key role in the pathogenesis of high-dose GSPE-induced cytotoxicity. PMID:16555001

Shao, Z H; Hsu, C W; Chang, W T; Waypa, G B; Li, J; Li, D; Li, C Q; Anderson, T; Qin, Y; Schumacker, P T; Becker, L B; Hoek, T L Vanden

2006-05-01

86

Study the cytotoxicity of different kinds of water-soluble nanoparticles in human osteoblast-like MG-63 cells  

SciTech Connect

Highlights: ? Preparation of three kinds of water-soluble QDs: CdTe, CdTe@SiO{sub 2}, Mn:ZnSe. ? Evaluated the cytotoxicity qualitatively and quantitatively. ? Fluorescent staining. ? Detected the total intracellular cadmium in cells. -- Abstract: Quantum nanoparticles have been applied extensively in biological and medical fields, the cytotoxicity of nanoparticles becomes the key point we should concern. In this paper, the cytotoxicity of three kinds of water-soluble nanoparticles: CdTe, CdTe@SiO{sub 2} and Mn:ZnSe was studied. We evaluated the nanoparticles toxicity qualitatively by observing the morphological changes of human osteoblast-like MG-63 cells at different incubation times and colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were carried out to detect the cell viability quantitatively. The results showed that CdTe nanoparticles with high concentrations caused cells to die largely while CdTe@SiO{sub 2} and Mn:ZnSe nanoparticles had no obvious effect. For further study, we studied the relation between the cell viability and the total cadmium concentration in cells and found that the viability of cells treated with CdTe@SiO{sub 2} nanoparticles was higher than that treated with CdTe nanoparticles. We also discovered that the death rate of cells co-incubated with CdTe nanoparticles was proportional to the total intracellular cadmium concentrations.

Niu, Lu [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)] [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Li, Yang; Li, Xiaojie [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun 130012 (China)] [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun 130012 (China); Gao, Xue [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)] [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Su, Xingguang, E-mail: suxg@jlu.edu.cn [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)] [Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)

2012-11-15

87

Computer-aided nanotoxicology: assessing cytotoxicity of nanoparticles under diverse experimental conditions by using a novel QSTR-perturbation approach  

NASA Astrophysics Data System (ADS)

Nowadays, the interest in the search for new nanomaterials with improved electrical, optical, catalytic and biological properties has increased. Despite the potential benefits that can be gathered from the use of nanoparticles, only little attention has been paid to their possible toxic effects that may affect human health. In this context, several assays have been carried out to evaluate the cytotoxicity of nanoparticles in mammalian cells. Owing to the cost in both resources and time involved in such toxicological assays, there has been a considerable increase in the interest towards alternative computational methods, like the application of quantitative structure-activity/toxicity relationship (QSAR/QSTR) models for risk assessment of nanoparticles. However, most QSAR/QSTR models developed so far have predicted cytotoxicity against only one cell line, and they did not provide information regarding the influence of important factors rather than composition or size. This work reports a QSTR-perturbation model aiming at simultaneously predicting the cytotoxicity of different nanoparticles against several mammalian cell lines, and also considering different times of exposure of the cell lines, as well as the chemical composition of nanoparticles, size, conditions under which the size was measured, and shape. The derived QSTR-perturbation model, using a dataset of 1681 cases (nanoparticle-nanoparticle pairs), exhibited an accuracy higher than 93% for both training and prediction sets. In order to demonstrate the practical applicability of our model, the cytotoxicity of different silica (SiO2), nickel (Ni), and nickel(ii) oxide (NiO) nanoparticles were predicted and found to be in very good agreement with experimental reports. To the best of our knowledge, this is the first attempt to simultaneously predict the cytotoxicity of nanoparticles under multiple experimental conditions by applying a single unique QSTR model.Nowadays, the interest in the search for new nanomaterials with improved electrical, optical, catalytic and biological properties has increased. Despite the potential benefits that can be gathered from the use of nanoparticles, only little attention has been paid to their possible toxic effects that may affect human health. In this context, several assays have been carried out to evaluate the cytotoxicity of nanoparticles in mammalian cells. Owing to the cost in both resources and time involved in such toxicological assays, there has been a considerable increase in the interest towards alternative computational methods, like the application of quantitative structure-activity/toxicity relationship (QSAR/QSTR) models for risk assessment of nanoparticles. However, most QSAR/QSTR models developed so far have predicted cytotoxicity against only one cell line, and they did not provide information regarding the influence of important factors rather than composition or size. This work reports a QSTR-perturbation model aiming at simultaneously predicting the cytotoxicity of different nanoparticles against several mammalian cell lines, and also considering different times of exposure of the cell lines, as well as the chemical composition of nanoparticles, size, conditions under which the size was measured, and shape. The derived QSTR-perturbation model, using a dataset of 1681 cases (nanoparticle-nanoparticle pairs), exhibited an accuracy higher than 93% for both training and prediction sets. In order to demonstrate the practical applicability of our model, the cytotoxicity of different silica (SiO2), nickel (Ni), and nickel(ii) oxide (NiO) nanoparticles were predicted and found to be in very good agreement with experimental reports. To the best of our knowledge, this is the first attempt to simultaneously predict the cytotoxicity of nanoparticles under multiple experimental conditions by applying a single unique QSTR model. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01285b

Luan, Feng; Kleandrova, Valeria V.; González-Díaz, Humberto; Ruso, Juan M.; Melo, André; Speck-Planche, Alejandro; Cordeiro, M. Natália D. S.

2014-08-01

88

Effect of surface functionality of silica nanoparticles on cellular uptake and cytotoxicity.  

PubMed

Mesoporous silica nanoparticles (MCM-41) with different surface chemistry were used as carrier system to study its influence on drug delivery and anticancer activity of curcumin (CUR). CUR was encapsulated in pristine MCM-41 (hydrophilic and negatively charged), amino functionalized MCM-41 (MCM-41-NH2 which is hydrophilic and positively charged), and methyl functionalized MCM-41 (MCM-41-CH3 which is hydrophobic and negatively charged) and evaluated for in vitro release and cell cytotoxicity in human squamous cell carcinoma cell line (SCC25). Various techniques were employed to evaluate the performance of these materials on cellular uptake and anticancer activity in the SCC25 cell line. Both positively and negatively charged surfaces demonstrated enhanced drug release and anticancer activity compared to pure CUR. Positively charged nanoparticles showed higher cell uptake compared to negatively charged nanoparticles owing to its electrostatic interaction with cells. However, hydrophobic surface modified nanoparticles (MCM-41-CH3) showed no improvement in drug release and anticancer activity due to its poor wetting effect. Cell cycle analysis and cell apoptosis studies revealed different pathway mechanisms followed by the positively and negatively charged nanoparticles but exhibiting similar anticancer activity in SCC25 cells. PMID:25166282

Jambhrunkar, Siddharth; Qu, Zhi; Popat, Amirali; Yang, Jie; Noonan, Owen; Acauan, Luiz; Ahmad Nor, Yusilawati; Yu, Chengzhong; Karmakar, Surajit

2014-10-01

89

L-Leucine for gold nanoparticles synthesis and their cytotoxic effects evaluation.  

PubMed

This work reports the preparation of water-soluble leucine capped gold nanoparticles by two single-step synthesis methods. The first procedure involves a citrate reduction approach where the citrate is used as reducing agent and leucine as capping/stabilizing agent. Different sizes of gold nanoparticles, citrate reduced and stabilized by leucine, Leu-AuNPs-C, with the mean diameters in the range of 21-56 nm, were obtained by varying the macroscopic parameters such as: concentration of the gold precursor solution, Au (III):citrate molar ratio and leucine pH. In the second procedure, leucine acts both as reducing and stabilizing agent, allowing us to obtain spherical gold nanoparticles, Leu-AuNPs, with a majority of 80 % (with the mean diameter of 63 nm). This proves that leucine is an appropriate reductant for the formation of water-soluble and stable gold nanoparticles colloids. The characterization of the leucine coated gold nanoparticles was carried out by TEM, UV-Vis and FT-IR analysis. The cytotoxic effect of Leu-AuNPs-C and Leu-AuNPs was also evaluated. PMID:25092048

Berghian-Grosan, Camelia; Olenic, Liliana; Katona, Gabriel; Perde-Schrepler, Maria; Vulcu, Adriana

2014-11-01

90

Biosynthesis of gold nanoparticles using Sargassum swartzii and its cytotoxicity effect on HeLa cells  

NASA Astrophysics Data System (ADS)

In this investigation, biological synthesis of gold nanoparticles (AuNPs) using Sargassum swartzii and its cytotoxicity against human cervical carcinoma (HeLa) cells is reported. The biological synthesis involved the reduction of chloroauric acid led to the formation of AuNPs within 5 min at 60 °C and the formation of AuNPs was confirmed using UV-vis spectrophotometer. The AuNPs were stable; spherical in shape with well-defined dimensions, and the average size of the particle is 35 nm. A zeta potential value of -27.6 mV revealed synthesized AuNPs were highly stable. The synthesized AuNPs exhibited a dose-dependent cytotoxicity against human cervical carcinoma (HeLa) cells. Furthermore, induction of apoptosis was measured by DAPI (4?,6-Diamidino-2-phenylindole dihydrochloride) staining.

Dhas, T. Stalin; Kumar, V. Ganesh; Karthick, V.; Govindaraju, K.; Shankara Narayana, T.

2014-12-01

91

Effects of fullerenol nanoparticles on acetamiprid induced cytoxicity and genotoxicity in cultured human lung fibroblasts.  

PubMed

The aim of this study was to investigate the effects of water soluble fullerene (fullerenol) nanoparticles on the in vitro genotoxicity induced by the insecticide acetamiprid. Healthy human lung cells (IMR-90) were treated with fullerenol C60(OH)n (n: 18-22) alone and in combination with acetamiprid for 24h. The micronucleus test, comet assay and ?-H2AX foci formation assays were used as genotoxicity endpoints. Cytotoxicity was evaluated using the clonogenic assay. The maximum tested concentration of fullerenol (1.600 ?g/ml) induced 77% survival where as the lowest concentration (25 ?g/ml) was not cytotoxic where as acetamiprid was cytotoxic. Fullerenol did not induce genotoxicity at tested concentrations (50-1600 ?g/L). On the other hand, acetamiprid (>50 ?M) significantly induced formation of micronuclei, and double and single stranded DNA breaks in IMR-90 cells. For simultaneous exposure studies, two non-cytotoxic concentrations (50 and 200 ?g/ml) of fullerenol and three cytotoxic concentrations of acetamiprid (100, 200 and 400 ?M) were selected. As a result, we observed that co-exposure with fullerenol significantly reduced the cytotoxicity and genotoxicity of acetamiprid in IMR-90 cells. Our results indicated the protective effect of water soluble fullerene particles on herbicide induced genotoxicity. PMID:25175643

Çava?, Tolga; Çink?l?ç, Nilüfer; Vatan, Özgür; Y?lmaz, Dilek

2014-09-01

92

Photoexcitation of tumor-targeted corroles induces singlet oxygen-mediated augmentation of cytotoxicity  

PubMed Central

The tumor-targeted corrole particle, HerGa, displays preferential toxicity to tumors in vivo and can be tracked via fluorescence for simultaneous detection, imaging, and treatment. We have recently uncovered an additional feature of HerGa in that its cytotoxicity is enhanced by light irradiation. In the present study, we have elucidated the cellular mechanisms for HerGa photoexcitation-mediated cell damage using fluorescence optical imaging. In particular, we found that light irradiation of HerGa produces singlet oxygen, causing mitochondrial damage and cytochrome c release, thus promoting apoptotic cell death. An understanding of the mechanisms of cell death induced by HerGa, particularly under conditions of light-mediated excitation, may direct future efforts in further customizing this nanoparticle for additional therapeutic applications and enhanced potency. PMID:23041277

Hwang, Jae Youn; Lubow, David J.; Chu, David; Sims, Jessica; Alonso-Valenteen, Felix; Gray, Harry B.; Gross, Zeev; Farkas, Daniel L.; Medina-Kauwe, Lali K.

2012-01-01

93

Anti-platelet agents augment cisplatin nanoparticle cytotoxicity by enhancing tumor vasculature permeability and drug delivery  

NASA Astrophysics Data System (ADS)

Tumor vasculature is critically dependent on platelet mediated hemostasis and disruption of the same can augment delivery of nano-formulation based chemotherapeutic agents which depend on enhanced permeability and retention for tumor penetration. Here, we evaluated the role of Clopidogrel, a well-known inhibitor of platelet aggregation, in potentiating the tumor cytotoxicity of cisplatin nano-formulation in a murine breast cancer model. In vivo studies in murine syngeneic 4T1 breast cancer model showed a significant greater penetration of macromolecular fluorescent nanoparticles after clopidogrel pretreatment. Compared to self-assembling cisplatin nanoparticles (SACNs), combination therapy with clopidogrel and SACN was associated with a 4 fold greater delivery of cisplatin to tumor tissue and a greater reduction in tumor growth as well as higher survival rate. Clopidogrel enhances therapeutic efficiency of novel cisplatin based nano-formulations agents by increasing tumor drug delivery and can be used as a potential targeting agent for novel nano-formulation based chemotherapeutics.

Pandey, Ambarish; Sarangi, Sasmit; Chien, Kelly; Sengupta, Poulomi; Papa, Anne-Laure; Basu, Sudipta; Sengupta, Shiladitya

2014-11-01

94

Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes  

SciTech Connect

The lethal hit induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by /sup 45/Ca tracer measurements after loading the myocytes with /sup 45/Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. It is concluded that infection of cultured myocytes with mengovirus predisposes them to attack by mengovirus specific CTL, and that persistent dysfunction of the myocyte is preceded by reversible changes in membrane potential and contraction. This is suggestive of an altered calcium handling by the myocytes possibly resulting in the cytotoxic effect.

Hassin, D.; Fixler, R.; Shimoni, Y.; Rubinstein, E.; Raz, S.; Gotsman, M.S.; Hasin, Y.

1987-01-01

95

Rapid mobilization of cytotoxic lymphocytes induced by dasatinib therapy.  

PubMed

Tyrosine kinase inhibitors (TKIs) have potent effects on malignant cells, and they also target kinases in normal cells, which may have therapeutic implications. Using a collection of 55 leukemia patients treated with TKI therapy (chronic myeloid leukemia, n=47; acute lymphoblastic leukemia, n=8), we found that dasatinib, a second-generation broad-spectrum TKI, induced a rapid, dose-dependent and substantial mobilization of non-leukemic lymphocytes and monocytes in blood peaking 1-2 h after an oral intake and the blood counts closely mirrored drug plasma concentration. A preferential mobilization was observed for natural killer (NK), NK T, B and ??+ T cells. Mobilization was coupled with a more effective transmigration of leukocytes through an endothelial cell layer and improved cytotoxicity of NK cells. Platelet numbers decreased markedly after the drug intake in a proportion of patients. Similar effects on blood cell dynamics and function were not observed with any other TKI (imatinib, nilotinib and bosutinib). Thus, dasatinib induces a unique, rapid mobilization and activation of cytotoxic, extravasation-competent lymphocytes, which may not only enhance antileukemia immune responses but can also be causally related to the side-effect profile of the drug (pleural effusions, thrombocytopenia). PMID:23192016

Mustjoki, S; Auvinen, K; Kreutzman, A; Rousselot, P; Hernesniemi, S; Melo, T; Lahesmaa-Korpinen, A-M; Hautaniemi, S; Bouchet, S; Molimard, M; Smykla, R; Lee, F Y; Vakkila, J; Jalkanen, S; Salmi, M; Porkka, K

2013-04-01

96

Effect of seabuckthorn on sodium nitroprusside-induced cytotoxicity in murine macrophages  

Microsoft Academic Search

The present study reports the anti-oxidant activity of alcoholic extracts of leaf and fruit of seabuckthorn (SBT) on nitric oxide (NO) induced cytotoxicity in J-774 macrophages. Sodium nitroprusside (SNP), which generates NO at the concentration of 500 ?g\\/ml, induced cytotoxicity as revealed by decreased neutral red uptake by macrophages. The cytotoxicity of SNP was attributed to enhanced reactive oxygen species (ROS)

S. Geetha; M. Sai Ram; Virendra Singh; G. Ilavazhagan; R. C. Sawhney

2002-01-01

97

Magnetic nanoparticles sensitize MCF-7 breast cancer cells to doxorubicin-induced apoptosis  

PubMed Central

Background Resistance of breast cancer cells to the available chemotherapeutics is a major obstacle to successful treatment. Recent studies have shown that magnetic nanoparticles might have significant application in different medical fields including cancer treatment. The goal of this study is to verify the ability of magnetic nanoparticles to sensitize cancer cells to the clinically available chemotherapy. Methods The role of iron oxide nanoparticles, static magnetic field, or a combination in the enhancement of the apoptotic potential of doxorubicin against the resistant breast cancer cells, MCF-7 was evaluated using the MTT assay and the propidium iodide method. Results In the present study, results revealed that pre-incubation of MCF-7 cells with iron oxide nanoparticles before the addition of doxorubicin did not enhance doxorubicin-induced growth inhibition. Pre-incubation of MCF-7 cells with iron oxide nanoparticles followed by a static magnetic field exposure significantly (P?induced cytotoxicity. Sensitization with pre-exposure to the magnetic field was dose-dependent where the highest cytotoxicity was seen at 1 tesla. Further experiments revealed that the anti-proliferative effect of this treatment procedure is due to induction of apoptotic cell death. Conclusions These results might point to the importance of combining magnetic nanoparticles with a static magnetic field in treatment of doxorubicin-refractory breast cancer cells. PMID:22533492

2012-01-01

98

Controllable synthesis of monodispersed silver nanoparticles as standards for quantitative assessment of their cytotoxicity.  

PubMed

Silver nanoparticles (Ag NPs) are appealing due to their excellent antibacterial/antivirus properties. At the meantime, the wide applications of Ag NPs as antibacterial/antivirus agents arise the concern of Ag NPs' toxicity. However, quantitative understanding of the cytotoxicity of Ag NPs is minimum since that the Ag NPs in current studies have wide size distributions, in which the size effect of Ag NPs on cytotoxicity was unable to be accurately evaluated. In this work, unprecedentedly monodispersed Ag NPs with sizes of 25, 35, 45, 60 and 70 nm were obtained, respectively, by using an optimized polyol method with poly(vinyl pyrrolidone) (PVP) as surfactant. It was found that the reaction temperature, reaction time, concentration of the surfactant and reactants are playing important roles in determining the size and size distribution of Ag NPs. With the monodispersed Ag NPs as standard samples, the size- and dose- dependent cytotoxicity of Ag NPs against Human lung fibroblast (HLF) cells was accurately accomplished in terms of cell viability, apoptosis and necrosis, reactive oxygen species, etc. We expect that the monodispersed Ag NPs will act as the standard samples for quantitatively characterizing the toxicity of Ag NPs in vitro and in vivo. PMID:22137123

Li, Lun; Sun, Jie; Li, Xiaoran; Zhang, Yan; Wang, Zhaoxu; Wang, Chunren; Dai, Jianwu; Wang, Qiangbin

2012-02-01

99

Assessing carbon-encapsulated iron nanoparticles cytotoxicity in Lewis lung carcinoma cells.  

PubMed

Carbon-encapsulated iron nanoparticles (CEINs) have been considered as attractive candidates for several biomedical applications. In the present study, we synthesized CEINs (the mean diameter 40-80?nm) using a carbon arc route, and the as-synthesized CEINs were characterized (scanning and transmission electron microscopy, dynamic light scattering, turbidimetry, Zeta potential) and further tested as raw and purified nanomaterials containing the carbon surface modified with acidic groups. For cytotoxicity evaluation, we applied a battery of different methods (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase, calcein AM/propidium iodide, annexin V/propidium iodide, JC-1, cell cycle assay, Zeta potential, TEM and inductively coupled plasma mass spectrometry) to address the strategic cytotoxic endpoints of Lewis lung carcinoma cells due to CEIN (0.0001-100?µg?ml(-1) ) exposures in vitro. Our studies evidence that incubation of Lewis lung carcinoma cells with CEINs is accompanied in substantial changes of zeta potential in cells and these effects may result in different internalization profiles. The results show that CEINs increased the mitochondrial and cell membrane cytotoxicity; however, the raw CEIN material (Fe@C/Fe) produced higher toxicities than the rest of the CEINs studied to data. The study showed that non-modified CEINs (Fe@C/Fe and Fe@C) elevated some pro-apoptotic events to a greater extent compared to that of the surface-modified CEINs (Fe@C-COOH and Fe@C-(CH2 )2 COOH). They also diminished the mitochondrial membrane potentials. In contrast to non-modified CEINs, the surface-functionalized nanoparticles caused the concentration- and time-dependent arrest of the S phase in cells. Taken all together, our results shed new light on the rational design of CEINs, as their geometry, hydrodynamic and, in particular, surface characteristics are important features in selecting CEINs as future nanomaterials for nanomedicine applications. PMID:24474239

Grudzinski, Ireneusz P; Bystrzejewski, Michal; Cywinska, Monika A; Kosmider, Anita; Poplawska, Magdalena; Cieszanowski, Andrzej; Fijalek, Zbigniew; Ostrowska, Agnieszka; Parzonko, Andrzej

2014-04-01

100

Cytotoxicity of surface-functionalized silicon and germanium nanoparticles: the dominant role of surface charges.  

PubMed

Although it is frequently hypothesized that surface (like surface charge) and physical characteristics (like particle size) play important roles in cellular interactions of nanoparticles (NPs), a systematic study probing this issue is missing. Hence, a comparative cytotoxicity study, quantifying nine different cellular endpoints, was performed with a broad series of monodisperse, well characterized silicon (Si) and germanium (Ge) NPs with various surface functionalizations. Human colonic adenocarcinoma Caco-2 and rat alveolar macrophage NR8383 cells were used to clarify the toxicity of this series of NPs. The surface coatings on the NPs appeared to dominate the cytotoxicity: the cationic NPs exhibited cytotoxicity, whereas the carboxylic acid-terminated and hydrophilic PEG- or dextran-terminated NPs did not. Within the cationic Si NPs, smaller Si NPs were more toxic than bigger ones. Manganese-doped (1% Mn) Si NPs did not show any added toxicity, which favors their further development for bioimaging. Iron-doped (1% Fe) Si NPs showed some added toxicity, which may be due to the leaching of Fe(3+) ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be the target for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such an imbalance led to a series of other cellular events for cationic NPs, like decreased mitochondrial membrane potential (??m) and ATP production, induction of ROS generation, increased cytoplasmic Ca(2+) content, production of TNF-? and enhanced caspase-3 activity. Taken together, the results explain the toxicity of Si NPs/Ge NPs largely by their surface characteristics, provide insight into the mode of action underlying the observed cytotoxicity, and give directions on synthesizing biocompatible Si and Ge NPs, as this is crucial for bioimaging and other applications in for example the field of medicine. PMID:23619571

Bhattacharjee, Sourav; Rietjens, Ivonne M C M; Singh, Mani P; Atkins, Tonya M; Purkait, Tapas K; Xu, Zejing; Regli, Sarah; Shukaliak, Amber; Clark, Rhett J; Mitchell, Brian S; Alink, Gerrit M; Marcelis, Antonius T M; Fink, Mark J; Veinot, Jonathan G C; Kauzlarich, Susan M; Zuilhof, Han

2013-06-01

101

Cytotoxicity of Surface-functionalized Silicon and Germanium Nanoparticles: The Dominant Role of Surface Charges  

PubMed Central

Although it is hypothesized that surface (like surface charge) and physical characteristics (like particle size) play important roles in cellular interactions of nanoparticles (NPs), a systematic study probing this issue is missing. Hence, a comparative cytotoxicity study quantifying nine different cellular endpoints, was performed with a broad series of monodisperse, well characterized silicon (Si) and germanium (Ge) NPs with various surface functionalizations. Human colonic adenocarcinoma Caco-2 and rat alveolar macrophage NR8383 cells were used, to clarify the toxicity of this series of NPs. The surface coatings on the NPs appeared to dominate the cytotoxicity: the cationic NPs exhibited cytotoxicity, whereas the carboxylic acid-terminated and hydrophilic PEG- or dextran-terminated NPs did not. Within the cationic Si NPs, smaller Si NPs were more toxic than bigger ones. Manganese-doped (1 % Mn) Si NPs did not show any added toxicity, which favors their further development for bioimaging. Iron-doped (1 % Fe) Si NPs showed some added toxicity, which may be due to the leaching of Fe3+ ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be a target organ for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such imbalance led to a series of other cellular events for cationic NPs, like decreased mitochondrial membrane potential (??m) and ATP production, induction of ROS generation, increased cytoplasmic Ca2+ content, production of TNF-? and enhanced caspase-3 activity. Taken together, the results explain the toxicity of Si NPs/Ge NPs largely by their surface characteristics, provide insight in the mode of action underlying the observed cytotoxicity, and give directions on synthesizing biocompatible Si and Ge NPs, as this is crucial for bioimaging and other applications in for example the field of medicine. PMID:23619571

Bhattacharjee, Sourav; Rietjens, Ivonne MCM; Singh, Mani P; Atkins, Tonya M; Purkait, Tapas K; Xu, Zejing; Regli, Sarah; Shukaliak, Amber; Clark, Rhett J; Mitchell, Brian S; Alink, Gerrit M; Marcelis, Antonius TM; Fink, Mark J; Veinot, Jonathan GC; Kauzlarich, Susan M; Zuilhofa, Han

2013-01-01

102

Effect of seabuckthorn on sodium nitroprusside-induced cytotoxicity in murine macrophages.  

PubMed

The present study reports the anti-oxidant activity of alcoholic extracts of leaf and fruit of seabuckthorn (SBT) on nitric oxide (NO) induced cytotoxicity in J-774 macrophages. Sodium nitroprusside (SNP), which generates NO at the concentration of 500 microg/ml, induced cytotoxicity as revealed by decreased neutral red uptake by macrophages. The cytotoxicity of SNP was attributed to enhanced reactive oxygen species (ROS) production, which in turn resulted in decrease in anti-oxidant levels. Alcoholic leaf and fruit extracts of SBT at the concentration of 500 microg/ml were found to have a significant cytoprotective effect against SNP-induced oxidative stress. These extracts inhibited SNP-induced cytotoxicity, free radical production and maintained the anti-oxidant status identical to that of control cells. The alcoholic fruit extract of SBT was found to have significantly higher anti-oxidant activity than leaf extract against SNP-induced cytotoxicity in murine macrophages. PMID:12481983

Geetha, S; Ram, M Sai; Singh, Virendra; Ilavazhagan, G; Sawhney, R C

2002-11-01

103

Antibacterial activity and cytotoxicity of multi-walled carbon nanotubes decorated with silver nanoparticles  

PubMed Central

Recently, various nanoscale materials, including silver (Ag) nanoparticles, have been actively studied for their capacity to effectively prevent bacterial growth. A critical challenge is to enhance the antibacterial properties of nanomaterials while maintaining their biocompatibility. The conjugation of multiple nanomaterials with different dimensions, such as spherical nanoparticles and high-aspect-ratio nanotubes, may increase the target-specific antibacterial capacity of the consequent nanostructure while retaining an optimal biocompatibility. In this study, multi-walled carbon nanotubes (MWCNTs) were treated with a mixture of acids and decorated with Ag nanoparticles via a chemical reduction of Ag cations by ethanol solution. The synthesized Ag-MWCNT complexes were characterized by transmission electron microscopy, X-ray diffractometry, and energy-dispersive X-ray spectroscopy. The antibacterial function of Ag-MWCNTs was evaluated against Methylobacterium spp. and Sphingomonas spp. In addition, the biocompatibility of Ag-MWCNTs was evaluated using both mouse liver hepatocytes (AML 12) and human peripheral blood mononuclear cells. Finally, we determined the minimum amount of Ag-MWCNTs required for a biocompatible yet effective antibacterial treatment modality. We report that 30 ?g/mL of Ag-MWCNTs confers antibacterial functionality while maintaining minimal cytotoxicity toward both human and animal cells. The results reported herein would be beneficial for researchers interested in the efficient preparation of hybrid nanostructures and in determining the minimum amount of Ag-MWCNTs necessary to effectively hinder the growth of bacteria. PMID:25336943

Seo, Youngmin; Hwang, Jangsun; Kim, Jieun; Jeong, Yoon; Hwang, Mintai P; Choi, Jonghoon

2014-01-01

104

Mycoplasma pneumoniae induces cytotoxic activity in guinea pig bronchoalveolar cells  

SciTech Connect

Precultured guinea pig alveolar macrophages (AM) and freshly harvested alveolar cells (FHAC) activated by interaction with Mycoplasma pneumoniae were cytotoxic for xenogeneic /sup 75/selenomethionine-labeled tumor target cells. Phagocytosis of whole opsonized or nonopsonized M. pneumoniae cells was more effective in eliciting cytotoxicity than uptake of sonicated microorganisms. The addition of living mycoplasma cells to the assay system enhanced the cytotoxic effect considerably. Target cells were significantly more susceptible to the cytotoxic action of phagocytes if they were coated with mycoplasma antigen or cocultured together with M. pneumoniae. The activation of the phagocytes could be inhibited by 2-deoxy-D-glucose but not by antimicrobial substances suppressing mycoplasma protein synthesis. It was accompanied by /sup 51/Cr release without detectable signs of cell damage. The supernatants of activated cells were cytotoxic for approximately 24 h. Inhibition, release, and cytotoxic activity indicate the necessity of an intact metabolism of the effector cells and suggest a secretion of cytotoxic substances.

Kist, M.; Koester, H.; Bredt, W.

1985-06-01

105

Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release  

PubMed Central

Background Silver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials. A wide range of toxicity studies have been performed on various AgNPs, but these studies report a high variation in toxicity and often lack proper particle characterization. The aim of this study was to investigate size- and coating-dependent toxicity of thoroughly characterized AgNPs following exposure of human lung cells and to explore the mechanisms of toxicity. Methods BEAS-2B cells were exposed to citrate coated AgNPs of different primary particle sizes (10, 40 and 75 nm) as well as to 10 nm PVP coated and 50 nm uncoated AgNPs. The particle agglomeration in cell medium was investigated by photon cross correlation spectroscopy (PCCS); cell viability by LDH and Alamar Blue assay; ROS induction by DCFH-DA assay; genotoxicity by alkaline comet assay and ?H2AX foci formation; uptake and intracellular localization by transmission electron microscopy (TEM); and cellular dose as well as Ag release by atomic absorption spectroscopy (AAS). Results The results showed cytotoxicity only of the 10 nm particles independent of surface coating. In contrast, all AgNPs tested caused an increase in overall DNA damage after 24 h assessed by the comet assay, suggesting independent mechanisms for cytotoxicity and DNA damage. However, there was no ?H2AX foci formation and no increased production of intracellular reactive oxygen species (ROS). The reasons for the higher toxicity of the 10 nm particles were explored by investigating particle agglomeration in cell medium, cellular uptake, intracellular localization and Ag release. Despite different agglomeration patterns, there was no evident difference in the uptake or intracellular localization of the citrate and PVP coated AgNPs. However, the 10 nm particles released significantly more Ag compared with all other AgNPs (approx. 24 wt% vs. 4–7 wt%) following 24 h in cell medium. The released fraction in cell medium did not induce any cytotoxicity, thus implying that intracellular Ag release was responsible for the toxicity. Conclusions This study shows that small AgNPs (10 nm) are cytotoxic for human lung cells and that the toxicity observed is associated with the rate of intracellular Ag release, a ‘Trojan horse’ effect. PMID:24529161

2014-01-01

106

Metabolic profiling reveals disorder of carbohydrate metabolism in mouse fibroblast cells induced by titanium dioxide nanoparticles.  

PubMed

As titanium dioxide (TiO(2)) nanoparticles are widely used commercially, their potential biosafety and metabolic mechanism needs to be fully explained. In this study, the cytotoxicity of homogeneous and weakly aggregated (< 100?nm) TiO(2) nanoparticles was investigated by analyzing the changes in metabolite profiles both in mouse fibroblast (L929) cells and their corresponding culture media using gas chromatograph with a time-of-flight mass spectrometry (GC/TOFMS)-based metabolomic strategy. With multivariate statistics analysis, satisfactory separations were observed in principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models. Based on the variable importance in the OPLS-DA models, a series of differential metabolites were identified by comparison between TiO(2) nanoparticle-treated L929 cells or their corresponding culture media and the control groups. It was found that the major biochemical metabolism (carbohydrate metabolism) was suppressed in TiO(2) nanoparticle-treated L929 cells and their corresponding culture media. These results might account for the serious damage to energy metabolism in mitochondria and the increased cellular oxidation stress in TiO(2) nanoparticle-induced L929 cells. These results also suggest that the metabolomic strategy had a great potential in evaluating the cytotoxicity of TiO(2) nanoparticles and thus was very helpful in understanding its underlying molecular mechanisms. PMID:22996321

Jin, Chengyu; Liu, Yumin; Sun, Limin; Chen, Tianlu; Zhang, Yinan; Zhao, Aihua; Wang, Xiaoyan; Cristau, Melanie; Wang, Kaisheng; Jia, Wei

2013-12-01

107

Preparation, characterization, cytotoxicity, and genotoxicity evaluations of thiolated- and s-nitrosated superparamagnetic iron oxide nanoparticles: implications for cancer treatment.  

PubMed

Iron oxide magnetic nanoparticles have been proposed for an increasing number of biomedical applications, such as drug delivery. To this end, toxicological studies of their potent effects in biological media must be better evaluated. The aim of this study was to synthesize, characterize, and examine the potential in vitro cytotoxicity and genotoxicity of thiolated (SH) and S-nitrosated (S-NO) iron oxide superparamagnetic nanoparticles toward healthy and cancer cell lines. Fe3O4 nanoparticles were synthesized by coprecipitation techniques and coated with small thiol-containing molecules, such as mercaptosuccinic acid (MSA) or meso-2,3-dimercaptosuccinic acid (DMSA). The physical-chemical, morphological, and magnetic properties of thiol-coating Fe3O4 nanoparticles were characterized by different techniques. The thiol groups on the surface of the nanoparticles were nitrosated, leading to the formation of S-nitroso-MSA- or S-nitroso-DMSA-Fe3O4 nanoparticles. The cytotoxicity and genotoxicity of thiolated and S-nitrosated nanoparticles were more deeply evaluated in healthy (3T3, human lymphocytes cells, and chinese hamster ovary cells) and cancer cell lines (MCF-7). The results demonstrated that thiol-coating iron oxide magnetic nanoparticles have few toxic effects in cells, whereas S-nitrosated-coated particles did cause toxic effects. Moreover, due to the superaramagnetic behavior of S-nitroso-Fe3O4 nanoparticles, those particles can be guided to the target site upon the application of an external magnetic field, leading to local toxic effects in the tumor cells. Taken together, the results suggest the promise of S-nitroso-magnetic nanoparticles in cancer treatment. PMID:24949992

Seabra, Amedea B; Pasquôto, Tatiane; Ferrarini, Ana Carolina F; Santos, Marconi da Cruz; Haddad, Paula S; de Lima, Renata

2014-07-21

108

Molecular Determinants of Apoptosis Induced by the Cytotoxic Ribonuclease Onconase: Evidence for Cytotoxic Mechanisms Different from Inhibition of Protein Synthesis1  

Microsoft Academic Search

Cytotoxic endoribonucleases (RNases) possess a potential for use in cancer therapy. However, the molecular determinants of RNase-induced cell death are not well understood. In this work, we identify such deter- minants of the cytotoxicity induced by onconase, an amphibian cytotoxic RNase. Onconase displayed a remarkable specificity for tRNA in vivo, leaving rRNA and mRNA apparently undamaged. Onconase-treated cells displayed apoptosis-associated

Mihail S. Iordanov; Olga P. Ryabinina; John Wong; Thanh-Hoai Dinh; Dianne L. Newton; Susanna M. Rybak; Bruce E. Magun

2000-01-01

109

The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles  

PubMed Central

Many types of nanoparticles (NPs) are tested for use in medical products, particularly in imaging and gene and drug delivery. For these applications, cellular uptake is usually a prerequisite and is governed in addition to size by surface characteristics such as hydrophobicity and charge. Although positive charge appears to improve the efficacy of imaging, gene transfer, and drug delivery, a higher cytotoxicity of such constructs has been reported. This review summarizes findings on the role of surface charge on cytotoxicity in general, action on specific cellular targets, modes of toxic action, cellular uptake, and intracellular localization of NPs. Effects of serum and intercell type differences are addressed. Cationic NPs cause more pronounced disruption of plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells ingest cationic NPs to a higher extent, but charge density and hydrophobicity are equally important; phagocytic cells preferentially take up anionic NPs. Cells do not use different uptake routes for cationic and anionic NPs, but high uptake rates are usually linked to greater biological effects. The different uptake preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs may influence the efficacy and selectivity of NPs for drug delivery and imaging. PMID:23144561

Frohlich, Eleonore

2012-01-01

110

Anti-platelet agents augment cisplatin nanoparticle cytotoxicity by enhancing tumor vasculature permeability and drug delivery.  

PubMed

Tumor vasculature is critically dependent on platelet mediated hemostasis and disruption of the same can augment delivery of nano-formulation based chemotherapeutic agents which depend on enhanced permeability and retention for tumor penetration. Here, we evaluated the role of Clopidogrel, a well-known inhibitor of platelet aggregation, in potentiating the tumor cytotoxicity of cisplatin nano-formulation in a murine breast cancer model. In vivo studies in murine syngeneic 4T1 breast cancer model showed a significant greater penetration of macromolecular fluorescent nanoparticles after clopidogrel pretreatment. Compared to self-assembling cisplatin nanoparticles (SACNs), combination therapy with clopidogrel and SACN was associated with a 4 fold greater delivery of cisplatin to tumor tissue and a greater reduction in tumor growth as well as higher survival rate. Clopidogrel enhances therapeutic efficiency of novel cisplatin based nano-formulations agents by increasing tumor drug delivery and can be used as a potential targeting agent for novel nano-formulation based chemotherapeutics. PMID:25302488

Pandey, Ambarish; Sarangi, Sasmit; Chien, Kelly; Sengupta, Poulomi; Papa, Anne-Laure; Basu, Sudipta; Sengupta, Shiladitya

2014-11-01

111

Sunflower oil mediated biomimetic synthesis and cytotoxicity of monodisperse hexagonal silver nanoparticles.  

PubMed

In this work, sunflower oil was utilized for the biomimetic synthesis of silver (Ag) nanoparticles (NPs), leading to highly mono-dispersed hexagonal-shaped silver nanoparticles (NPs) at various concentrations. It was found that the biomolecules of the oil not only have the capability to reduce silver ions, due to its extended phenolic system, but also appear to recognize and affect the Ag nanocrystal growth on the (110) face, leading to hexagonal growth of the NPs of 50nm size. Initially, some spherical AgNPs of less than 10nm diameter were observed; however, over a longer period of time, a majority of hexagonal-shaped nanocrystals were formed. The one step synthesis can be extended for other metals. The as prepared sunflower oil capped AgNPs being completely free of toxic chemicals can be directly utilized for in vitro studies and offer a more rational approach for cellular applications. The NP solution exhibited dose-dependent cytotoxicity in human lung carcinoma cells and physiologically relevant cell model (3T3L1cells). PMID:25280698

Thakore, Sonal; Rathore, Puran Singh; Jadeja, Ravirajsinh N; Thounaojam, Menaka; Devkar, Ranjitsinh V

2014-11-01

112

Co-nanoencapsulation of magnetic nanoparticles and selol for breast tumor treatment: in vitro evaluation of cytotoxicity and magnetohyperthermia efficacy  

PubMed Central

Antitumor activities have been described in selol, a hydrophobic mixture of molecules containing selenium in their structure, and also in maghemite magnetic nanoparticles (MNPs). Both selol and MNPs were co-encapsulated within poly(lactic-co-glycolic acid) (PLGA) nanocapsules for therapeutic purposes. The PLGA-nanocapsules loaded with MNPs and selol were labeled MSE-NC and characterized by transmission and scanning electron microscopy, electrophoretic mobility, photon correlation spectroscopy, presenting a monodisperse profile, and positive charge. The antitumor effect of MSE-NC was evaluated using normal (MCF-10A) and neoplastic (4T1 and MCF-7) breast cell lines. Nanocapsules containing only MNPs or selol were used as control. MTT assay showed that the cytotoxicity induced by MSE-NC was dose and time dependent. Normal cells were less affected than tumor cells. Cell death occurred mainly by apoptosis. Further exposure of MSE-NC treated neoplastic breast cells to an alternating magnetic field increased the antitumor effect of MSE-NC. It was concluded that selol-loaded magnetic PLGA-nanocapsules (MSE-NC) represent an effective magnetic material platform to promote magnetohyperthermia and thus a potential system for antitumor therapy. PMID:23055734

Estevanato, Luciana LC; Silva, Jaqueline R Da; Falqueiro, Andre M; Mosiniewicz-Szablewska, Ewa; Suchocki, Piotr; Tedesco, Antonio C; Morais, Paulo C; Lacava, Zulmira GM

2012-01-01

113

Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells  

PubMed Central

The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins. PMID:25192420

Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi

2014-01-01

114

Herpes Simplex Virus Type 1 Renders Infected Cells Resistant to Cytotoxic T-Lymphocyte-Induced Apoptosis  

Microsoft Academic Search

Many viruses interfere with apoptosis of infected cells, presumably preventing cellular apoptosis as a direct response to viral infection. Since cytotoxic T lymphocytes (CTL) induce apoptosis of infected cells as part of the \\

KEITH R. JEROME; JONATHAN F. TAIT; DAVID M. KOELLE; LAWRENCE COREY

1998-01-01

115

Comparative Cytotoxic Evaluation of Free and Sodium Alginate Nanoparticle-Encapsulated ICD-85 on Primary Lamb Kidney Cells  

PubMed Central

Background Current anti-cancer drug therapy results in systemic side effects due to non-specific uptake by normal healthy noncancerous tissues. To alleviate this difficulty, many attempts have been devoted to the development of new delivery systems such as polymeric Nanoparticles (NPs). In this study, we prepared ICD-85 NPs based on sodium alginate and analyzed the cytotoxic activity of ICD-85 NPs relative to free ICD-85 on primary lamb kidney cells. Methods ICD-85 loaded sodium alginate nanoparticles were prepared by ionic gelation method and were characterized by the particle size, size distribution and Fourier Transform Infrared (FT-IR) spectroscopy. The in vitro cytotoxicity was evaluated by MTT assay and membrane integrity was evaluated by measuring Lactate Dehydrogenase (LDH) activity. The morphological alterations of untreated and treated cells were assessed by light inverted microscope. Results MTT assay showed that ICD-85 NPs could significantly decrease the in vitro cytotoxicity on primary lamb kidney cells compared to the free ICD-85. The IC10 value at 72 hours was increased from 9±2.7 ?g/ml for free ICD-85 to 52±4.3 ?g/ml for ICD-85 NPs. LDH assay demonstrated that free ICD-85 had dose-dependent cytotoxicity on primary lamb kidney cells while ICD-85 NPs exhibited significantly decreased cytotoxicity at equivalent concentrations. Moreover, morphological analysis showed no significant difference between control and treated cells with ICD-85 NPs. Conclusion Based on the results obtained in the present study it can be concluded that encapsulation of ICD-85 with sodium alginate nanoparticles can reduce its necrotic effect on primary lamb kidney cells.

Zare Mirakabadi, Abbas; Moradhaseli, Saeed

2013-01-01

116

Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract.  

PubMed

Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50) value of 23.83±1.1 ?g/mL (HepG2), 18.75±2.1 ?g/mL (MCF-7), 12.5±1.7 ?g/mL (HeLa), and 6.4±2.3 ?g/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer. PMID:24899805

Namvar, Farideh; Rahman, Heshu Sulaiman; Mohamad, Rosfarizan; Baharara, Javad; Mahdavi, Mahnaz; Amini, Elaheh; Chartrand, Max Stanley; Yeap, Swee Keong

2014-01-01

117

cytotoxic T cells kill infected cells directly by inducing them to undergo apoptosis helper T cells help activate B cells, macrophages and cytotoxic T cells.  

E-print Network

cytotoxic T cells kill infected cells directly by inducing them to undergo apoptosis helper T cells help activate B cells, macrophages and cytotoxic T cells. Both classes of T cells express cell-surface, antibodylike receptors, encoded by genes that are assembled from multiple gene segments during T cell

Morante, Silvia

118

Evaluation of cytotoxic, genotoxic and inflammatory response in human alveolar and bronchial epithelial cells exposed to titanium dioxide nanoparticles.  

PubMed

The toxicity of titanium dioxide nanoparticles (TiO2 -NPs), used in several applications, seems to be influenced by their specific physicochemical characteristics. Cyto-genotoxic and inflammatory effects induced by a mixture of 79% anatase/21% rutile TiO2 -NPs were investigated in human alveolar (A549) and bronchial (BEAS-2B) cells exposed to 1-40?µg?ml(-1) 30?min, 2 and 24?h to assess potential pulmonary toxicity. The specific physicochemical properties such as crystallinity, NP size and shape, agglomerate size, surface charge and specific surface area (SSA) were analysed. Cytotoxic effects were studied by evaluating cell viability using the WST1 assay and membrane damage using LDH analysis. Direct/oxidative DNA damage was assessed by the Fpg-comet assay and the inflammatory potential was evaluated as interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-? release by enzyme-linked immunosorbant assay (ELISA). In A549 cells no significant viability reduction and moderate membrane damage, only at the highest concentration, were detected, whereas BEAS-2B cells showed a significant viability reduction and early membrane damage starting from 10?µg?ml(-1) . Direct/oxidative DNA damage at 40?µg?ml(-1) and increased IL-6 release at 5?µg?ml(-1) were found only in A549 cells after 2?h. The secretion of pro-inflammatory cytokine IL-6, involved in the early acute inflammatory response, and oxidative DNA damage indicate the promotion of early and transient oxidative-inflammatory effects of tested TiO2 -NPs on human alveolar cells. The findings show a higher susceptibility of normal bronchial cells to cytotoxic effects and higher responsiveness of transformed alveolar cells to genotoxic, oxidative and early inflammatory effects induced by tested TiO2 -NPs. This different cell behaviour after TiO2 -NPs exposure suggests the use of both cell lines and multiple end-points to elucidate NP toxicity on the respiratory system. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25224607

Ursini, Cinzia Lucia; Cavallo, Delia; Fresegna, Anna Maria; Ciervo, Aureliano; Maiello, Raffaele; Tassone, Paola; Buresti, Giuliana; Casciardi, Stefano; Iavicoli, Sergio

2014-11-01

119

Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells  

PubMed Central

Background Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA) by flow cytometry. Results RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation. Conclusion RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling. PMID:16216126

Bossios, Apostolos; Psarras, Stelios; Gourgiotis, Dimitrios; Skevaki, Chrysanthi L; Constantopoulos, Andreas G; Saxoni-Papageorgiou, Photini; Papadopoulos, Nikolaos G

2005-01-01

120

Mixed molecular weight copolymer nanoparticles for the treatment of drug-resistant tumors: formulation development and cytotoxicity.  

PubMed

Nanoparticles composed of both high- and low-molecular-weight methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL) diblock copolymers (termed "mixed molecular weight nanoparticles") were investigated for the encapsulation and delivery of the taxane drugs paclitaxel (PTX) and docetaxel (DTX). These nanoparticles were prepared using nanoprecipitation and emulsion methods. These 80 nm nanoparticles were prepared with high yields, efficiently solubilized PTX and DTX up to 500 and 1300 ?g/mL, respectively, and demonstrated controlled release of these drugs over 14 days. The taxane-sensitive (MDCKII) and taxane-resistant [P-glycoprotein (P-gp) overexpressing] MDCKII-MDR cell lines were used to establish the cytotoxic profiles of these nanoparticles. Because of the coencapsulation of the previously demonstrated P-gp inhibitor, a low-molecular-weight MePEG-b-PCL copolymer (MePEG17 -b-PCL5 ), these drug-loaded mixed molecular weight nanoparticles dramatically reduced the viability of P-gp overexpressing MDCKII-MDR cells and restored sensitivity to taxane drugs in these cells. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3966-3976, 2014. PMID:25318668

Wan, Chung Ping Leon; Letchford, Kevin; Leung, Donna; Jackson, John K; Burt, Helen M

2014-12-01

121

Hepatotoxicity and liver injury induced by hydroxyapatite nanoparticles.  

PubMed

As hydroxyapatite nanoparticles (HA NPs) are increasingly used in biomedical and biotechnological fields, risk assessment of HA NPs has attracted extensive attention. Nevertheless, little is known about the potential adverse effects of HA NPs on normal hepatocytes and the liver. In the present study, we conducted an in vitro study in which 80-nm HA NPs were incubated with normal Buffalo rat liver (BRL) cells. By analyzing the changes in cell viability, apoptosis/necrosis and the mitogen-activated protein kinase (MAPK) signaling pathway, we investigated the cytotoxicity and potential mechanism of HA NPs in hepatocytes. Furthermore, we used the serum hematology and histopathology examinations to explore the in vivo effects of HA NPs on the structure and function of the liver. Our results showed that exposure to HA NPs at a concentration above 200?µg?ml(-1) decreased cell viability, increased levels of lactate dehydrogenase (LDH) leakage, induced apoptosis and necrosis, and triggered the MAPK signaling pathway in BRL cells in a dose-dependent manner. Moreover, our in vivo study indicated that HA NPs increased the white blood cell count (WBC) and the levels of tumor necrosis factor-? (TNF-?), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum, caused inflammatory cell infiltration at the portal area in the liver, and induced hepatic oxidative stress with elevated levels of hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA). These data demonstrate that at certain concentrations, 80-nm HA NPs cause hepatotoxicity and liver injury. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25225040

Chen, Qingqing; Xue, Yang; Sun, Jiao

2014-11-01

122

Protective Effects of Anethole Dithiolethione against Oxidative Stress-induced Cytotoxicity in Human Jurkat T Cells  

Microsoft Academic Search

The protective effects of anethole dithiolethione (ADT) against H2O2- or 4-hydroxynonenal (HNE)-induced cytotoxicity in human Jurkat T cells were investigated. Jurkat T cells were pretreated with ADT (10–50 ?M) for 18 hr and then challenged with H2O2 or HNE for up to 4 hr. Cytotoxicity was assessed by measuring: 1) leakage of lactate dehydrogenase from cells to medium; and 2)

Savita Khanna; Chandan K Sen; Sashwati Roy; Marie-Odile Christen; Lester Packer

1998-01-01

123

Use of a Rapid Cytotoxicity Screening Approach to Engineer a Safer Zinc Oxide Nanoparticle through Iron Doping  

PubMed Central

The establishment of verifiably safe nanotechnology requires the development of assessment tools to identify hazardous nanomaterial properties that could be modified to improve nanomaterial safety. While there is a lot of debate of what constitutes appropriate safety screening methods, one approach is to use the assessment of cellular injury pathways to collect knowledge about hazardous material properties that could lead to harm to humans and the environment. We demonstrate the use of a multi-parameter cytotoxicity assay that evaluates toxic oxidative stress to compare the effects of titanium dioxide (TiO2), cerium oxide (CeO2) and zinc oxide (ZnO) nanoparticles in bronchial epithelial and macrophage cell lines. The nanoparticles were chosen based on their volume of production and likelihood of spread to the environment. Among the materials, dissolution of ZnO nanoparticles and Zn2+ release were capable of ROS generation and activation of an integrated cytotoxic pathway that includes intracellular calcium flux, mitochondrial depolarization, and plasma membrane leakage. These responses were chosen based on the compatibility of the fluorescent dyes that contemporaneously assess their response characteristics by a semi-automated epifluorescence procedure. Purposeful reduction of ZnO cytotoxicity was achieved by iron doping, which changed the material matrix to slow Zn2+ release. In summary, we demonstrate the utility of a rapid throughput, integrated biological oxidative stress response pathway to perform hazard ranking of a small batch of metal oxide nanoparticles, in addition to showing how this assay can be used to improve nanosafety by decreasing ZnO dissolution through Fe doping. PMID:20043640

George, Saji; Pokhrel, Suman; Xia, Tian; Gilbert, Benjamin; Ji, Zhaoxia; Schowalter, Marco; Rosenauer, Andreas; Damoiseaux, Robert; Bradley, Kenneth A; Madler, Lutz; Nel, Andre E

2014-01-01

124

Oxidative stress induced by pure and iron-doped amorphous silica nanoparticles in subtoxic conditions.  

PubMed

Amorphous silica nanoparticles (SiO?-NPs) have found broad applications in industry and are currently intensively studied for potential uses in medical and biomedical fields. Several studies have reported cytotoxic and inflammatory responses induced by SiO?-NPs in different cell types. The present study was designed to examine the association of oxidative stress markers with SiO?-NP induced cytotoxicity in human endothelial cells. We used pure monodisperse amorphous silica nanoparticles of two sizes (16 and 60 nm; S16 and S60) and a positive control, iron-doped nanosilica (16 nm; SFe), to study the generation of hydroxyl radicals (HO·) in cellular-free conditions and oxidative stress in cellular systems. We investigated whether SiO?-NPs could influence intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, increase lipid peroxidation (malondialdehyde (MDA) and 4-hydroxyalkenal (HAE) concentrations), and up-regulate heme oxygenase-1 (HO-1) mRNA expression in the studied cells. None of the particles, except SFe, produced ROS in cell-free systems. We found significant modifications for all parameters in cells treated with SFe nanoparticles. At cytotoxic doses of S16 (40-50 ?g/mL), we detected weak alterations of intracellular glutathione (4 h) and a marked induction of HO-1 mRNA (6 h). Cytotoxic doses of S60 elicited similar responses. Preincubation of cells being exposed to SiO?-NPs with an antioxidant (5 mM N-acetylcysteine, NAC) significantly reduced the cytotoxic activity of S16 and SFe (when exposed up to 25 and 50 ?g/mL, respectively) but did not protect cells treated with S60. Preincubation with NAC significantly reduced HO-1 mRNA expression in cells treated with SFe but did not have any effect on HO-1 mRNA level in cell exposed to S16 and S60. Our study demonstrates that the chemical composition of the silica nanoparticles is a dominant factor in inducing oxidative stress. PMID:22263782

Napierska, Dorota; Rabolli, Virginie; Thomassen, Leen C J; Dinsdale, David; Princen, Catherine; Gonzalez, Laetitia; Poels, Katrien L C; Kirsch-Volders, Micheline; Lison, Dominique; Martens, Johan A; Hoet, Peter H

2012-04-16

125

Green synthesis of silver nanoparticles using Ganoderma neo-japonicum Imazeki: a potential cytotoxic agent against breast cancer cells  

PubMed Central

Background Silver nanoparticles (AgNPs) are an important class of nanomaterial for a wide range of industrial and biomedical applications. AgNPs have been used as antimicrobial and disinfectant agents due their detrimental effect on target cells. The aim of our study was to determine the cytotoxic effects of biologically synthesized AgNPs using hot aqueous extracts of the mycelia of Ganoderma neo-japonicum Imazeki on MDA-MB-231 human breast cancer cells. Methods We developed a green method for the synthesis of water-soluble AgNPs by treating silver ions with hot aqueous extract of the mycelia of G. neo-japonicum. The formation of AgNPs was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. Furthermore, the toxicity of synthesized AgNPs was evaluated using a series of assays: such as cell viability, lactate dehydrogenase leakage, reactive oxygen species generation, caspase 3, DNA laddering, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling in human breast cancer cells (MDA-MB-231). Results The ultraviolet-visible absorption spectroscopy results showed a strong resonance centered on the surface of AgNPs at 420 nm. The X-ray diffraction analysis confirmed that the synthesized AgNPs were single-crystalline, corresponding with the result of transmission electron microscopy. Treatment of MDA-MB-231 breast cancer cells with various concentrations of AgNPs (1–10 ?g/mL) for 24 hours revealed that AgNPs could inhibit cell viability and induce membrane leakage in a dose-dependent manner. Cells exposed to AgNPs showed increased reactive oxygen species and hydroxyl radical production. Furthermore, the apoptotic effects of AgNPs were confirmed by activation of caspase 3 and DNA nuclear fragmentation. Conclusion The results indicate that AgNPs possess cytotoxic effects with apoptotic features and suggest that the reactive oxygen species generated by AgNPs have a significant role in apoptosis. The present findings suggest that AgNPs could contribute to the development of a suitable anticancer drug, which may lead to the development of a novel nanomedicine for the treatment of cancers. PMID:24265551

Gurunathan, Sangiliyandi; Raman, Jegadeesh; Malek, Sri Nurestri Abd; John, Priscilla A; Vikineswary, Sabaratnam

2013-01-01

126

Study of cadmium-induced cytotoxicity using two-photon excitation endogenous fluorescence  

E-print Network

Study of cadmium-induced cytotoxicity using two-photon excitation endogenous fluorescence microscopy, the cadmium Cd - induced cellular toxic level can be assessed by the free-to protein- bound excited at 730 nm is captured at different times following exposure to cadmium at a variety

Qu, Jianan

127

In vitro evaluation of cellular response induced by manufactured nanoparticles.  

PubMed

"Nanoparticle" is defined as the particles whose diameter in at least one dimension is less than 100 nm. Compared with fine-particles, nanoparticles have large specific surface area. There is a dramatic increase over fine-particles in chemical and physical activities, such as ion release, adsorption ability, and ROS production. These properties are important for industrial use, and many nanoparticles are already used in products familiar to consumers as sunscreens and cosmetics. However, nanoparticle properties beneficial to the industry may also induce biological influences, including toxic activities. Recently, many investigations about the toxicology of nanoparticles have been reported. In the evaluation of nanoparticles toxicity, in vitro studies give us important information, especially in terms of toxic mechanisms. In vitro studies showed that some nanoparticles induce oxidative stress, apoptosis, production of cytokines, and cell death. There are reports that cellular influences of other nanoparticles are small. There are also reports of different results, some with low and some with high influences, for the same nanoparticle. One of the causes of this inconsistency might be a diremption of the living body influence study and the characterization study. Characterization of individual nanoparticles and their dispersions are essential for in vitro evaluation of their biological effects since each nanoparticle shows unique chemical and physical properties. Particularly, the aggregation state and metal ion release ability of nanoparticles affect its cellular influences. Reports concerning the characterization in the in vitro toxicity assessment are increasing. For an accurate risk assessment of nanoparticles, in this review, we outline recent studies of in vitro evaluation of cellular influences induced by nanoparticles. Moreover, we also introduce current studies about the characterization methods of nanoparticles and their dispersions for toxicological evaluation. PMID:22136515

Horie, Masanori; Kato, Haruhisa; Fujita, Katsuhide; Endoh, Shigehisa; Iwahashi, Hitoshi

2012-03-19

128

INHIBITORS OF HYDROPEROXIDE METABOLISM ENHANCE ASCORBATE-INDUCED CYTOTOXICITY  

PubMed Central

Pharmacological ascorbate, via its oxidation, has been proposed as a pro-drug for the delivery of H2O2 to tumors. Pharmacological ascorbate decreases clonogenic survival of pancreatic cancer cells, which can be reversed by treatment with scavengers of H2O2. The goal of this study was to determine if inhibitors of intracellular hydroperoxide detoxification could enhance the cytotoxic effects of ascorbate. Human pancreatic cancer cells were treated with ascorbate alone or in combination with inhibitors of hydroperoxide removal including the glutathione disulfide reductase inhibitor 1,3 bis (2-chloroethyl)-1-nitrosurea (BCNU), siRNA targeted to glutathione disulfide reductase (siGR), and 2-deoxy-D-glucose (2DG), which inhibits glucose metabolism. Changes in the intracellular concentration of H2O2 were determined by analysis of the rate of aminotriazole-mediated inactivation of endogenous catalase activity. Pharmacological ascorbate increased intracellular H2O2 and depleted intracellular glutathione. When inhibitors of H2O2 metabolism were combined with pharmacological ascorbate the increase in intracellular H2O2 was amplified and cytotoxicity was enhanced. We conclude that inclusion of agents that inhibit cellular peroxide removal produced by pharmacological ascorbate leads to changes in the intracellular redox state resulting in enhanced cytotoxicity. PMID:23205739

Olney, Kristen E.; Du, Juan; van 't Erve, Thomas J.; Witmer, Jordan R.; Sibenaller, Zita A.; Wagner, Brett A.; Buettner, Garry R.; Cullen, Joseph J.

2013-01-01

129

Inhibitors of hydroperoxide metabolism enhance ascorbate-induced cytotoxicity.  

PubMed

Pharmacological ascorbate, via its oxidation, has been proposed as a pro-drug for the delivery of H(2)O(2) to tumors. Pharmacological ascorbate decreases clonogenic survival of pancreatic cancer cells, which can be reversed by treatment with scavengers of H(2)O(2). The goal of this study was to determine if inhibitors of intracellular hydroperoxide detoxification could enhance the cytotoxic effects of ascorbate. Human pancreatic cancer cells were treated with ascorbate alone or in combination with inhibitors of hydroperoxide removal including the glutathione disulfide reductase inhibitor 1,3 bis (2-chloroethyl)-1-nitrosurea (BCNU), siRNA targeted to glutathione disulfide reductase (siGR), and 2-deoxy-D-glucose (2DG), which inhibits glucose metabolism. Changes in the intracellular concentration of H(2)O(2) were determined by analysis of the rate of aminotriazole-mediated inactivation of endogenous catalase activity. Pharmacological ascorbate increased intracellular H(2)O(2) and depleted intracellular glutathione. When inhibitors of H(2)O(2) metabolism were combined with pharmacological ascorbate the increase in intracellular H(2)O(2) was amplified and cytotoxicity was enhanced. We conclude that inclusion of agents that inhibit cellular peroxide removal produced by pharmacological ascorbate leads to changes in the intracellular redox state resulting in enhanced cytotoxicity. PMID:23205739

Olney, K E; Du, J; van 't Erve, T J; Witmer, J R; Sibenaller, Z A; Wagner, B A; Buettner, G R; Cullen, J J

2013-03-01

130

Extracellular biosynthesis of silver nanoparticle using Streptomyces sp. 09 PBT 005 and its antibacterial and cytotoxic properties  

NASA Astrophysics Data System (ADS)

The application of microorganisms for the synthesis of nanoparticles as an eco-friendly and promising approach is welcome due to its non-toxicity and simplicity. The aim of this study was to synthesize silver nanoparticle using Streptomyces sp. (09 PBT 005). 09 PBT 005 was isolated from the soil sample of the agriculture field in Vengodu, Thiruvannamalai district, Tamil Nadu, India. 09 PBT 005 was subjected to molecular characterization by 16S rRNA sequence analysis. It was found that 09 PBT 005 belonged to Streptomyces sp. The isolate Streptomyces sp. 09 PBT 005 was inoculated in fermentation medium and incubated at 30 ºC for 12 days in different pH conditions. The 0.02 molar concentration showed good antibacterial activity against Gram-positive and Gram-negative bacteria at pH-7. The synthesis of silver nanoparticles was investigated by UV-Vis spectroscopy, scanning electron microscopy and Fourier Transform Infrared analysis. The synthesized AgNPs sizes were found to be in the dimensions ranging between 198 and 595 nm. The cytotoxicity of the synthesized nanoparticles was studied against A549 adenocarcinoma lung cancer cell line. It showed 83.23 % activity at 100 ?l with IC 50 value of 50 ?l. This method will be useful in the biosynthesis of nanoparticles.

Saravana Kumar, P.; Balachandran, C.; Duraipandiyan, V.; Ramasamy, D.; Ignacimuthu, S.; Al-Dhabi, Naif Abdullah

2014-03-01

131

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells  

PubMed Central

Background The increased use of engineered nanoparticles (NPs) has caused new concerns about the potential exposure to biological systems and the potential risk that these materials may pose on human health. Here, we examined the effects of exposure to different concentrations (0–50 ?g/mL) and incubation times (10 hours, 24 hours, or 48 hours) of yttrium oxide (Y2O3) NPs on human embryonic kidney (HEK293) cells. Changes in cellular morphology, cell viability, cell membrane integrity, reactive oxygen species levels, mitochondrial membrane potential, cell death (apoptosis and necrosis), and the DNA damage after NP exposure were compared to the effects seen following incubation with paraquat, a known toxicant. Results The 24-hour inhibitory concentration 50 (IC50) of Y2O3 NPs (41±5 nm in size) in the HEK293 cells was found to be 108 ?g/mL. Incubation with Y2O3 NPs (12.25–50 ?g/mL) increased the ratio of Bax/Bcl-2, caspase-3 expression and promoted apoptotic- and necrotic-mediated cell death in both a concentration and a time-dependent manner. Decreases in cell survivability were associated with elevations in cellular reactive oxygen species levels, increased mitochondrial membrane permeability, and evidence of DNA damage, which were consistent with the possibility that mitochondria impairment may play an important role in the cytotoxic response. Conclusion These data demonstrate that the Y2O3 NP exposure is associated with increased cellular apoptosis and necrosis in cultured HEK293 cells. PMID:24648735

Selvaraj, Vellaisamy; Bodapati, Sravanthi; Murray, Elizabeth; Rice, Kevin M; Winston, Nicole; Shokuhfar, Tolou; Zhao, Yu; Blough, Eric

2014-01-01

132

Preparation and Cytotoxic Evaluation of Magnetite (Fe3O4) Nanoparticles on Breast Cancer Cells and its Combinatory Effects with Doxorubicin used in Hyperthermia  

PubMed Central

Background Magnetic nanoparticles in a variable magnetic field are able to produce heat. This heat (42-45°C) has more selective effect on fast dividing cancer cells than normal tissues. Methods In this work magnetite nanoparticles have been prepared via co-precipitation and phase identification was performed by powder x-ray diffraction (XRD). Magnetic parameters of the prepared nanoparticles were measured by a Vibrating Sample Magnetometer (VSM). A sensitive thermometer has been used to measure the increase of temperature in the presence of an alternating magnetic field. To evaluate the cytotoxicity of nanoparticles, the suspended magnetite nanoparticles in liquid paraffin, doxorubicin and a mixture of both were added to the MDA-MB-468 cells in separate 15 ml tubes and left either in the RT or in the magnetic field for 30 min. Cell survival was measured by trypan blue exclusion assay and flow cytometer. Particle size distribution of the nanoparticles was homogeneous with a mean particles size of 10 nm. A 15°C temperature increase was achieved in presence of an AC magnetic field after 15 min irradiation. Results Biological results showed that magnetite nanoparticles alone were not cytotoxic at RT, while in the alternative magnetic filed more than 50% of cells were dead. Doxorubicin alone was not cytotoxic during 30 min, but in combination with magnetite more than 80% of the cells were killed. Conclusion It could be concluded that doxorubicin and magnetite nanoparticles in an AC magnetic field had combinatory effects against cells. PMID:23799178

Sadeghi-Aliabadi, Hojjat; Mozaffari, Morteza; Behdadfar, Behshid; Raesizadeh, Maryam; Zarkesh-Esfahani, Hamid

2013-01-01

133

Antibacterial and Cytotoxic Efficacy of Extracellular Silver Nanoparticles Biofabricated from Chromium Reducing Novel OS4 Strain of Stenotrophomonas maltophilia  

PubMed Central

Biofabricated metal nanoparticles are generally biocompatible, inexpensive, and ecofriendly, therefore, are used preferably in industries, medical and material science research. Considering the importance of biofabricated materials, we isolated, characterized and identified a novel bacterial strain OS4 of Stenotrophomonas maltophilia (GenBank: JN247637.1). At neutral pH, this Gram negative bacterial strain significantly reduced hexavalent chromium, an important heavy metal contaminant found in the tannery effluents and minings. Subsequently, even at room temperature the supernatant of log phase grown culture of strain OS4 also reduced silver nitrate (AgNO3) to generate nanoparticles (AgNPs). These AgNPs were further characterized by UV–visible, Nanophox particle size analyzer, XRD, SEM and FTIR. As evident from the FTIR data, plausibly the protein components of supernatant caused the reduction of AgNO3. The cuboid and homogenous AgNPs showed a characteristic UV-visible peak at 428 nm with average size of ?93 nm. The XRD spectra exhibited the characteristic Bragg peaks of 111, 200, 220 and 311 facets of the face centred cubic symmetry of nanoparticles suggesting that these nanoparticles were crystalline in nature. From the nanoparticle release kinetics data, the rapid release of AgNPs was correlated with the particle size and increasing surface area of the nanoparticles. A highly significant antimicrobial activity against medically important bacteria by the biofabricated AgNPs was also revealed as decline in growth of Staphylococcus aureus (91%), Escherichia coli (69%) and Serratia marcescens (66%) substantially. Additionally, different cytotoxic assays showed no toxicity of AgNPs to liver function, RBCs, splenocytes and HeLa cells, hence these particles were safe to use. Therefore, this novel bacterial strain OS4 is likely to provide broad spectrum benefits for curing chromium polluted sites, for biofabrication of AgNPs and ultimately in the nanoparticle based drug formulation for the treatment of infectious diseases. PMID:23555625

Oves, Mohammad; Khan, Mohammad Saghir; Zaidi, Almas; Ahmed, Arham S.; Ahmed, Faheem; Ahmad, Ejaz; Sherwani, Asif; Owais, Mohammad; Azam, Ameer

2013-01-01

134

Antibacterial and cytotoxic efficacy of extracellular silver nanoparticles biofabricated from chromium reducing novel OS4 strain of Stenotrophomonas maltophilia.  

PubMed

Biofabricated metal nanoparticles are generally biocompatible, inexpensive, and ecofriendly, therefore, are used preferably in industries, medical and material science research. Considering the importance of biofabricated materials, we isolated, characterized and identified a novel bacterial strain OS4 of Stenotrophomonas maltophilia (GenBank: JN247637.1). At neutral pH, this Gram negative bacterial strain significantly reduced hexavalent chromium, an important heavy metal contaminant found in the tannery effluents and minings. Subsequently, even at room temperature the supernatant of log phase grown culture of strain OS4 also reduced silver nitrate (AgNO3) to generate nanoparticles (AgNPs). These AgNPs were further characterized by UV-visible, Nanophox particle size analyzer, XRD, SEM and FTIR. As evident from the FTIR data, plausibly the protein components of supernatant caused the reduction of AgNO3. The cuboid and homogenous AgNPs showed a characteristic UV-visible peak at 428 nm with average size of ~93 nm. The XRD spectra exhibited the characteristic Bragg peaks of 111, 200, 220 and 311 facets of the face centred cubic symmetry of nanoparticles suggesting that these nanoparticles were crystalline in nature. From the nanoparticle release kinetics data, the rapid release of AgNPs was correlated with the particle size and increasing surface area of the nanoparticles. A highly significant antimicrobial activity against medically important bacteria by the biofabricated AgNPs was also revealed as decline in growth of Staphylococcus aureus (91%), Escherichia coli (69%) and Serratia marcescens (66%) substantially. Additionally, different cytotoxic assays showed no toxicity of AgNPs to liver function, RBCs, splenocytes and HeLa cells, hence these particles were safe to use. Therefore, this novel bacterial strain OS4 is likely to provide broad spectrum benefits for curing chromium polluted sites, for biofabrication of AgNPs and ultimately in the nanoparticle based drug formulation for the treatment of infectious diseases. PMID:23555625

Oves, Mohammad; Khan, Mohammad Saghir; Zaidi, Almas; Ahmed, Arham S; Ahmed, Faheem; Ahmad, Ejaz; Sherwani, Asif; Owais, Mohammad; Azam, Ameer

2013-01-01

135

The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion.  

PubMed

This investigation was designed to determine whether nano-sized manganese oxide (Mn-40 nm) particles would induce dopamine (DA) depletion in a cultured neuronal phenotype, PC-12 cells, similar to free ionic manganese (Mn(2+)). Cells were exposed to Mn-40 nm, Mn(2+) (acetate), or known cytotoxic silver nanoparticles (Ag-15 nm) for 24 h. Phase-contrast microscopy studies show that Mn-40 nm or Mn(2+) exposure did not greatly change morphology of PC-12 cells. However, Ag-15 nm and AgNO(3) produce cell shrinkage and irregular membrane borders compared to control cells. Further microscopic studies at higher resolution demonstrated that Mn-40 nm nanoparticles and agglomerates were effectively internalized by PC-12 cells. Mitochondrial reduction activity, a sensitive measure of particle and metal cytotoxicity, showed only moderate toxicity for Mn-40 nm compared to similar Ag-15 nm and Mn(2+) doses. Mn-40 nm and Mn(2+) dose dependently depleted DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), while Ag-15 nm only significantly reduced DA and DOPAC at concentrations of 50 mug/ml. Therefore, the DA depletion of Mn-40 nm was most similar to Mn(2+), which is known to induce concentration-dependent DA depletion. There was a significant increase (> 10-fold) in reactive oxygen species (ROS) with Mn-40 nm exposure, suggesting that increased ROS levels may participate in DA depletion. These results clearly demonstrate that nanoscale manganese can deplete DA, DOPAC, and HVA in a dose-dependent manner. Further study is required to evaluate the specific intracellular distribution of Mn-40 nm nanoparticles, metal dissolution rates in cells and cellular matrices, if DA depletion is induced in vivo, and the propensity of Mn nanoparticles to cross the blood-brain barrier or be selectively uptaken by nasal epithelium. PMID:16714391

Hussain, Saber M; Javorina, Amanda K; Schrand, Amanda M; Duhart, Helen M; Ali, Syed F; Schlager, John J

2006-08-01

136

Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity  

PubMed Central

Resistance to chemotherapy presents a serious challenge in the successful treatment of various cancers and is mainly responsible for mortality associated with disseminated cancers. Here we show that expression of HtrA1, which is frequently downregulated in ovarian cancer, influences tumor response to chemotherapy by modulating chemotherapy-induced cytotoxicity. Downregulation of HtrA1 attenuated cisplatin- and paclitaxel-induced cytotoxicity, while forced expression of HtrA1 enhanced cisplatin- and paclitaxel-induced cytotoxicity. HtrA1 expression was upregulated by both cisplatin and paclitaxel treatment. This upregulation resulted in limited autoproteolysis and activation of HtrA1. Active HtrA1 induces cell death in a serine protease–dependent manner. The potential role of HtrA1 as a predictive factor of clinical response to chemotherapy was assessed in both ovarian and gastric cancer patients receiving cisplatin-based regimens. Patients with ovarian or gastric tumors expressing higher levels of HtrA1 showed a higher response rate compared with those with lower levels of HtrA1 expression. These findings uncover what we believe to be a novel pathway by which serine protease HtrA1 mediates paclitaxel- and cisplatin-induced cytotoxicity and suggest that loss of HtrA1 in ovarian and gastric cancers may contribute to in vivo chemoresistance. PMID:16767218

Chien, Jeremy; Aletti, Giovanni; Baldi, Alfonso; Catalano, Vincenzo; Muretto, Pietro; Keeney, Gary L.; Kalli, Kimberly R.; Staub, Julie; Ehrmann, Michael; Cliby, William A.; Lee, Yean Kit; Bible, Keith C.; Hartmann, Lynn C.; Kaufmann, Scott H.; Shridhar, Viji

2006-01-01

137

Methylglyoxal-induced cytotoxicity in neonatal rat brain: a role for oxidative stress and MAP kinases.  

PubMed

Carbonyl compounds such as methylglyoxal (MGO) seem to play an important role in complications resulting from diabetes mellitus, in aging and neurodegenerative disorders. In this study, we are showing, that MGO is able to suppress cell viability and induce apoptosis in the cerebral cortex and hippocampus of neonatal rats ex-vivo. These effects are partially related with ROS production, evaluated by DCFH-DA assay. Coincubation of MGO and reduced glutathione (GSH) or Trolox (vitamin E) totally prevented ROS production but only partially prevented the MGO-induced decreased cell viability in the two brain structures, as evaluated by the MTT assay. Otherwise, L-NAME, a nitric oxide (NO) inhibitor, partially prevented ROS production in the two structures but partially prevented cytotoxicity in the hippocampus. Pharmacological inhibition of Erk, has totally attenuated MGO-induced ROS production and cytotoxicity, suggesting that MEK/Erk pathway could be upstream of ROS generation and cell survival. Otherwise, p38MAPK and JNK failed to prevent ROS generation but induced decreased cell survival consistent with ROS-independent mechanisms. We can propose that Erk, p38MAPK and JNK are involved in the cytotoxicity induced by MGO through different signaling pathways. While Erk could be an upstream effector of ROS generation, p38MAPK and JNK seem to be associated with ROS-independent cytotoxicity in neonatal rat brain. The cytotoxic damage progressed to apoptotic cell death at MGO concentration higher than those described for adult brain, suggesting that the neonatal brain is resistant to MGO-induced cell death. The consequences of MGO-induced brain damage early in life, remains to be clarified. However, it is feasible that high MGO levels during cortical and hippocampal development could be, at least in part, responsible for the impairment of cognitive functions in adulthood. PMID:23378107

Heimfarth, Luana; Loureiro, Samanta Oliveira; Pierozan, Paula; de Lima, Bárbara Ortiz; Reis, Karina Pires; Torres, Elisandra Barbosa; Pessoa-Pureur, Regina

2013-09-01

138

Assessment of Cr(VI)-Induced Cytotoxicity and Genotoxicity Using High Content Analysis  

PubMed Central

Oral exposure to high concentrations of hexavalent chromium [Cr(VI)] induces intestinal redox changes, villus cytotoxicity, crypt hyperplasia, and intestinal tumors in mice. To assess the effects of Cr(VI) in a cell model relevant to the intestine, undifferentiated (proliferating) and differentiated (confluent) Caco-2 cells were treated with Cr(VI), hydrogen peroxide or rotenone for 2–24 hours. DNA damage was then assessed by nuclear staining intensity of 8-hydroxydeoxyguanosine (8-OHdG) and phosphorylated histone variant H2AX (?-H2AX) measured by high content analysis methods. In undifferentiated Caco-2, all three chemicals increased 8-OHdG and ?-H2AX staining at cytotoxic concentrations, whereas only 8-OHdG was elevated at non-cytotoxic concentrations at 24 hr. Differentiated Caco-2 were more resistant to cytotoxicity and DNA damage than undifferentiated cells, and there were no changes in apoptotic markers p53 or annexin-V. However, Cr(VI) induced a dose-dependent translocation of the unfolded protein response transcription factor ATF6 into the nucleus. Micronucleus (MN) formation was assessed in CHO-K1 and A549 cell lines. Cr(VI) increased MN frequency in CHO-K1 only at highly cytotoxic concentrations. Relative to the positive control Mitomycin-C, Cr(VI) only slightly increased MN frequency in A549 at mildly cytotoxic concentrations. The results demonstrate that Cr(VI) genotoxicity correlates with cytotoxic concentrations, and that H2AX phosphorylation occurs at higher concentrations than oxidative DNA damage in proliferating Caco-2 cells. The findings suggest that in vitro genotoxicity of Cr(VI) is primarily oxidative in nature at low concentrations. Implications for in vivo intestinal toxicity of Cr(VI) will be discussed. PMID:22905163

Thompson, Chad M.; Fedorov, Yuriy; Brown, Daniel D.; Suh, Mina; Proctor, Deborah M.; Kuriakose, Liz; Haws, Laurie C.; Harris, Mark A.

2012-01-01

139

Dexamethasone-loaded Block Copolymer Nanoparticles Induce Leukemia Cell Death and Enhances Therapeutic Efficacy: A Novel Application in Pediatric Nanomedicine  

PubMed Central

Nanotechnology approaches have tremendous potential for enhancing treatment efficacy with lower doses of chemotherapeutics. Nanoparticle-based drug delivery approaches are poorly developed for childhood leukemia. Dexamethasone (Dex) is one of the most common chemotherapeutic drugs used in the treatment of childhood leukemia. In this study, we encapsulated Dex in polymeric nanoparticles and validated their anti-leukemic potential in vitro and in vivo. Nanoparticles (NPs) with an average diameter of 110 nm were assembled from amphiphilic block copolymers poly (ethylene glycol) (PEG) and poly (?-caprolactone) (PCL) bearing pendant cyclic ketals. The blank nanoparticles were non-toxic to cultured cells in vitro and to mice in vivo. Encapsulation of Dex into the nanoparticles (Dex-NP) did not compromise the bioactivity of the drug. Dex-NPs induced glucocorticoid phosphorylation and showed cytotoxicity similar to the free Dex in leukemic cells. Studies using nanoparticles labeled with fluorescent dyes revealed leukemic cell surface binding and internalization. In vivo biodistribution studies showed NP accumulation in the liver and spleen with subsequent clearance of the particles with time. In a pre-clinical model of leukemia, Dex-NPs significantly improved the quality of life and survival of mice compared to the free drug. To our knowledge, this is the first report showing the efficacy of polymeric nanoparticles to deliver Dex to potentially treat childhood leukemia and reveals that low dose of Dex should be sufficient for inducing cell death and improve survival. PMID:23194373

Krishnan, Vinu; Xu, Xian; Barwe, Sonali P.; Yang, Xiaowei; Czymmek, Kirk; Waldman, Scott A.; Mason, Robert W.; Jia, Xinqiao; Rajasekaran, Ayyappan K.

2014-01-01

140

Role of EGFR degradation in cisplatin-induced cytotoxicity in head and neck cancer  

PubMed Central

Cisplatin and its analogues are the most commonly used agents in the treatment of head and neck squamous cell carcinoma (HNSCC). In this study, we investigated a possible role of epidermal growth factor receptor (EGFR), phosphorylation and degradation in cisplatin-induced cytotoxicity. Cisplatin treatment led to an increase in initial EGFR phosphorylation at the Y1045, the binding site of ubiquitin ligase, Casitas B-lineage lymphoma (c-Cbl), followed by ubiquitination in the relatively cisplatin-sensitive cell lines. However, cisplatin-resistant cell lines underwent minimal EGFR phosphorylation at the Y1045 site and minimal ubiquitination. We found that EGFR degradation in response to cisplatin was highly correlated with cytotoxicity in seven head and neck cancer cell lines. Pretreatment with epidermal growth factor (EGF), enhanced cisplatin-induced EGFR degradation and cytotoxicity, whereas erlotinib pretreatment blocked EGFR phosphorylation, degradation, and cisplatin-induced cytotoxicity. Expression of a mutant Y1045F EGFR, which is relatively resistant to c-Cbl mediated degradation, in Chinese hamster ovary cells and the UMSCC11B human head and neck cancer cell line protected EGFR from cisplatin-induced degradation and enhanced cell survival compared to WT-EGFR. Transfection of WT-c-Cbl enhanced EGFR degradation and cisplatin-induced cytotoxicity compared to control vector. These results demonstrate that cisplatin-induced EGFR phosphorylation and subsequent ubiquitination and degradation is an important determinant of cisplatin sensitivity. Our findings suggest that treatment with an EGFR inhibitor before cisplatin would be antagonistic, as EGFR inhibition would protect EGFR from cisplatin-mediated phosphorylation and subsequent ubiquitination and degradation, which may explain the negative results of several recent clinical trials. Furthermore, they suggest that EGFR degradation is worth exploring as an early biomarker of response and as a target to improve outcome. PMID:20215522

Ahsan, A; Hiniker, SM; Ramanand, SG; Nyati, S; Hegde, A; Helman, A; Menawat, R; Bhojani, MS; Lawrence, TS; Nyati, MK

2010-01-01

141

Role of Reactive Oxygen Species on Diesel Exhaust Particle-Induced Cytotoxicity in Rat Cardiac Myocytes  

Microsoft Academic Search

Exposure to air pollution containing diesel exhaust particles (DEP) is associated with an increase in mortality rate attributed to cardiovascular diseases, but the mechanisms by which DEP produces adverse cardiovascular effects at the cellular level are not elucidated. This study investigated the cytotoxic mechanisms underlying DEP-induced neonatal rat cardiac myocytes effects in vitro, focusing on the role of reactive oxygen

Yuta Okayama; Masayoshi Kuwahara; Akira K. Suzuki; Hirokazu Tsubone

2006-01-01

142

Cytotoxicity of sophorolipid-gellan gum-gold nanoparticle conjugates and their doxorubicin loaded derivatives towards human glioma and human glioma stem cell lines.  

PubMed

Biocompatible gold nanoparticles were synthesized by using a naturally occurring gum--Gellan Gum--as a capping and reducing agent. These were further conjugated with sophorolipids which again were accessed through a biochemical transformation of a fatty acid. The cellular uptake of sophorolipid-conjugated gellan gum reduced gold nanoparticles and their cytotoxicity on human glioma cell line LN-229 and human glioma stem cell line HNGC-2 were investigated. Quite surprisingly even the simple sophorolipid-conjugated gellan gum reduced/capped gold nanoparticles showed greater efficacy in killing the glioma cell lines and, gratifyingly, the glioma stem cell lines also. The cytotoxic effects became more prominent once the anti cancer drug doxorubicin hydrochloride was also conjugated to these gold nanoparticles. PMID:21069248

Dhar, Sheetal; Reddy, E Maheswara; Prabhune, Asmita; Pokharkar, Varsha; Shiras, Anjali; Prasad, B L V

2011-02-01

143

Antibacterial and cytotoxic effect of biologically synthesized silver nanoparticles using aqueous root extract of Erythrina indica lam.  

PubMed

Simple, yet an effective and rapid approach for the green synthesis of silver nanoparticles (Ag NPs) using root extract of Erythrina indica and its in vitro antibacterial activity was tried against human pathogenic bacteria and its cytotoxic effect in breast and lung cancer cell lines has been demonstrated in this study. Various instrumental techniques were adopted to characterize the synthesized Ag NPs viz. UV-Vis (Ultra violet), FTIR (Fourier Transform Infrared), XRD (X-ray diffraction), DLS (Dynamic light scattering), HR TEM (High-resolution transmission electron microscopy), EDX (Energy-dispersive X-ray spectroscopy). Surface plasmon spectra for Ag NPs are centered nearly at 438 nm with dark brown color. FTIR analysis revealed the presence of terpenes, phenol, flavonols and tannin act as effective reducing and capping agents for converting silver nitrate to Ag NPs. The synthesized Ag NPs were found to be spherical in shape with size in the range of 20-118 nm. Moreover, the synthesized Ag NPs showed potent antibacterial activity against Gram positive and Gram negative bacteria and these biologically synthesized nanoparticles were also proved to exhibit excellent cytotoxic effect on breast and lung cancer cell lines. PMID:25189525

Rathi Sre, P R; Reka, M; Poovazhagi, R; Arul Kumar, M; Murugesan, K

2015-01-25

144

Docetaxel Loaded PEG-PLGA Nanoparticles: Optimized Drug Loading, In-vitro Cytotoxicity and In-vivo Antitumor Effect  

PubMed Central

In this study a 3-factor, 3-level Box-Behnken design was used to prepare optimized docetaxel (DTX) loaded pegylated poly lactide-co-glycolide (PEG-PLGA) Nanoparticles (NPs) with polymer concentration (X1), drug concentration (X2) and ratio of the organic to aqueous solvent (X3) as the independent variables and particle size (Y1), poly dispersity index (PDI) (Y2) and drug loading (Y3) as the responses. The cytotoxicity of optimized DTX loaded PEG-PLGA NPs was studied in SKOV3 tumor cell lines by standard MTT assay. The in-vivo antitumor efficacy of DTX loaded PLGA-PEG NPs was assessed in tumor bearing female BALB/c mice. The optimum level of Y1, Y2 and Y3 predicted by the model were 188 nm, 0.16 and 9% respectively with perfect agreement with the experimental data. The in-vitro release profile of optimum formulation showed a burst release of approximately 20% (w/w) followed by a sustained release profile of the loaded drug over 288 h. The DTX loaded optimized nanoparticles showed a greater cytotoxicity against SKOV3 cancer cells than free DTX. Enhanced tumor-suppression effects were achieved with DTX-loaded PEG-PLGA NPs. These results demonstrated that optimized NPs could be a potentially useful delivery system for DTX as an anticancer agent.

Noori Koopaei, Mona; Khoshayand, Mohammad Reza; Mostafavi, Seyed Hossein; Amini, Mohsen; Khorramizadeh, Mohammad Reza; Jeddi Tehrani, Mahmood; Atyabi, Fatemeh; Dinarvand, Rassoul

2014-01-01

145

Docetaxel Loaded PEG-PLGA Nanoparticles: Optimized Drug Loading, In-vitro Cytotoxicity and In-vivo Antitumor Effect.  

PubMed

In this study a 3-factor, 3-level Box-Behnken design was used to prepare optimized docetaxel (DTX) loaded pegylated poly lactide-co-glycolide (PEG-PLGA) Nanoparticles (NPs) with polymer concentration (X1), drug concentration (X2) and ratio of the organic to aqueous solvent (X3) as the independent variables and particle size (Y1), poly dispersity index (PDI) (Y2) and drug loading (Y3) as the responses. The cytotoxicity of optimized DTX loaded PEG-PLGA NPs was studied in SKOV3 tumor cell lines by standard MTT assay. The in-vivo antitumor efficacy of DTX loaded PLGA-PEG NPs was assessed in tumor bearing female BALB/c mice. The optimum level of Y1, Y2 and Y3 predicted by the model were 188 nm, 0.16 and 9% respectively with perfect agreement with the experimental data. The in-vitro release profile of optimum formulation showed a burst release of approximately 20% (w/w) followed by a sustained release profile of the loaded drug over 288 h. The DTX loaded optimized nanoparticles showed a greater cytotoxicity against SKOV3 cancer cells than free DTX. Enhanced tumor-suppression effects were achieved with DTX-loaded PEG-PLGA NPs. These results demonstrated that optimized NPs could be a potentially useful delivery system for DTX as an anticancer agent. PMID:25276182

Noori Koopaei, Mona; Khoshayand, Mohammad Reza; Mostafavi, Seyed Hossein; Amini, Mohsen; Khorramizadeh, Mohammad Reza; Jeddi Tehrani, Mahmood; Atyabi, Fatemeh; Dinarvand, Rassoul

2014-01-01

146

Retardation-induced plasmonic blinking in coupled nanoparticles  

E-print Network

Retardation-induced plasmonic blinking in coupled nanoparticles Holger Fischer* and Olivier J. F We study how retardation leads to interference effects in radiatively coupled plasmonic nanoparticles. We show that inclined illumination through a glass substrate on two plasmonic particles results

Floreano, Dario

147

Cytotoxicity of sophorolipid-gellan gum-gold nanoparticle conjugates and their doxorubicin loaded derivatives towards human glioma and human glioma stem cell lines  

Microsoft Academic Search

Biocompatible gold nanoparticles were synthesized by using a naturally occurring gum-Gellan Gum-as a capping and reducing agent. These were further conjugated with sophorolipids which again were accessed through a biochemical transformation of a fatty acid. The cellular uptake of sophorolipid-conjugated gellan gum reduced gold nanoparticles and their cytotoxicity on human glioma cell line LN-229 and human glioma stem cell line

Sheetal Dhar; E. Maheswara Reddy; Asmita Prabhune; Varsha Pokharkar; Anjali Shiras; B. L. V. Prasad

2011-01-01

148

Celecoxib-Induced Cytotoxic Effect Is Potentiated by Inhibition of Autophagy in Human Urothelial Carcinoma Cells  

PubMed Central

Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC) cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum (ER) stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine (3-MA), bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC. PMID:24349176

Ho, I-Lin; Chang, Hong-Chiang; Chuang, Yuan-Ting; Lin, Wei-Chou; Lee, Ping-Yi; Chang, Shih-Chen; Chiang, Chih-Kang; Pu, Yeong-Shiau; Chou, Chien-Tso; Hsu, Chen-Hsun; Liu, Shing-Hwa

2013-01-01

149

Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity  

PubMed Central

The latent HIV-1 reservoir remains the major barrier to HIV-1 eradication. Although successful at limiting HIV replication, highly active antiretroviral therapy is unable to cure HIV infection, thus novel therapeutic strategies are needed to eliminate the virus. Magnetic field hyperthermia (MFH) generates thermoablative cytotoxic temperatures in target-cell populations, and has delivered promising outcomes in animal models, as well as in several cancer clinical trials. MFH has been proposed as a strategy to improve the killing of HIV-infected cells and for targeting the HIV latent reservoirs. We wished to determine whether MFH could be used to enhance cytotoxic T-lymphocyte (CTL) targeting of HIV-infected cells in a proof-of-concept study. Here, for the first time, we apply MFH to an infectious disease (HIV-1) using the superparamagnetic iron oxide nanoparticle FeraSpin R. We attempt to improve the cytotoxic potential of T-cell receptor-transfected HIV-specific CTLs using thermotherapy, and assess superparamagnetic iron oxide nanoparticle toxicity, uptake, and effect on cell function using more sensitive methods than previously described. FeraSpin R exhibited only limited toxicity, demonstrated efficient uptake and cell-surface attachment, and only modestly impacted T-cell function. In contrast to the cancer models, insufficient MFH was generated to enhance CTL killing of HIV-infected cells. MFH remains an exciting new technology in the field of cancer therapeutics, which, as technology improves, may have significant potential to enhance CTL function and act as an adjunctive therapy in the eradication of latently infected HIV-positive cells. PMID:23901272

Williams, James P; Southern, Paul; Lissina, Anya; Christian, Helen C; Sewell, Andrew K; Phillips, Rodney; Pankhurst, Quentin; Frater, John

2013-01-01

150

The decrease of PAMAM dendrimer-induced cytotoxicity by PEGylation via attenuation of oxidative stress  

NASA Astrophysics Data System (ADS)

Due to their unique structure, poly(amidoamine) (PAMAM) dendrimers have been widely used in medical applications. However, PAMAM dendrimers bearing amino terminals show certain cytotoxicity. In order to improve their biocompatibility, we modified Generation-5 PAMAM dendrimers by conjugating them with poly(ethylene glycol) (PEG) of two different molecular weights and different number of chains. The IC50 values of PEGylated dendrimers were 12-105 fold higher than those of PAMAM dendrimers. To investigate the influence of PEGylation on PAMAM-induced cytotoxicity, the intracellular responses, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), and apoptosis were examined. The results indicated that conjugation with PEG could effectively reduce the PAMAM-induced cell apoptosis by attenuating the ROS production and inhibiting PAMAM-induced MMP collapse. Meanwhile, dendrimers conjugated with less PEG of lower molecular weight did not significantly change the endocytic properties. Dendrimers conjugated with more PEG of higher molecular weight were much less cytotoxic. This study provided a novel insight into the effects of PEGylation on the decrease of cytotoxicity at the molecular level.

Wang, Wei; Xiong, Wei; Wan, Jiangling; Sun, Xiaohui; Xu, Huibi; Yang, Xiangliang

2009-03-01

151

Digitoxin-induced cytotoxicity in cancer cells is mediated through distinct kinase and interferon signaling networks.  

PubMed

Cardiac glycosides (e.g., digoxin, digitoxin) constitute a diverse family of plant-derived sodium pump inhibitors that have been in clinical use for the treatment of heart-related diseases (congestive heart failure, atrial arrhythmia) for many years. Recently though, accumulating in vitro and in vivo evidence highlight potential anticancer properties of these compounds. Despite the fact that members of this family have advanced to clinical trial testing in cancer therapeutics, their cytotoxic mechanism is not yet elucidated. In this study, we investigated the cytotoxic properties of cardiac glycosides against a panel of pancreatic cancer cell lines, explored their apoptotic mechanism, and characterized the kinetics of cell death induced by these drugs. Furthermore, we deployed a high-throughput kinome screening approach and identified several kinases of the Na-K-ATPase-mediated signal transduction circuitry (epidermal growth factor receptor, Src, pkC, and mitogen-activated protein kinases) as important mediators downstream of cardiac glycoside cytotoxic action. To further extend our knowledge on their mode of action, we used mass-spectrometry-based quantitative proteomics (stable isotope labeling of amino acids in cell culture) coupled with bioinformatics to capture large-scale protein perturbations induced by a physiological dose of digitoxin in BxPC-3 pancreatic cancer cells and identified members of the interferon family as key regulators of the main protein/protein interactions downstream of digitoxin action. Hence, our findings provide more in-depth information regarding the molecular mechanisms underlying cardiac glycoside-induced cytotoxicity. PMID:21859838

Prassas, Ioannis; Karagiannis, George S; Batruch, Ihor; Dimitromanolakis, Apostolos; Datti, Alessandro; Diamandis, Eleftherios P

2011-11-01

152

Singlet oxygen mediated DNA degradation by copper nanoparticles: potential towards cytotoxic effect on cancer cells  

Microsoft Academic Search

The DNA degradation potential and anti-cancer activities of copper nanoparticles of 4-5 nm size are reported. A dose dependent\\u000a degradation of isolated DNA molecules by copper nanoparticles through generation of singlet oxygen was observed. Singlet oxygen\\u000a scavengers such as sodium azide and Tris [hydroxyl methyl] amino methane were able to prevent the DNA degradation action of\\u000a copper nanoparticles confirming the

Gregor P Jose; Subhankar Santra; Swadhin K Mandal; Tapas K Sengupta

2011-01-01

153

Effect of amorphous silica nanoparticles on in vitro RANKL-induced osteoclast differentiation in murine macrophages  

PubMed Central

Amorphous silica nanoparticles (nSP) have been used as a polishing agent and/or as a remineralization promoter for teeth in the oral care field. The present study investigates the effects of nSP on osteoclast differentiation and the relationship between particle size and these effects. Our results revealed that nSP exerted higher cytotoxicity in macrophage cells compared with submicron-sized silica particles. However, tartrate-resistant acid phosphatase (TRAP) activity and the number of osteoclast cells (TRAP-positive multinucleated cells) were not changed by nSP treatment in the presence of receptor activator of nuclear factor ?B ligand (RANKL) at doses that did not induce cytotoxicity by silica particles. These results indicated that nSP did not cause differentiation of osteoclasts. Collectively, the results suggested that nanosilica exerts no effect on RANKL-induced osteoclast differentiation of RAW264.7 cells, although a detailed mechanistic examination of the nSP70-mediated cytotoxic effect is needed. PMID:21777482

2011-01-01

154

Effect of amorphous silica nanoparticles on in vitro RANKL-induced osteoclast differentiation in murine macrophages.  

PubMed

Amorphous silica nanoparticles (nSP) have been used as a polishing agent and/or as a remineralization promoter for teeth in the oral care field. The present study investigates the effects of nSP on osteoclast differentiation and the relationship between particle size and these effects. Our results revealed that nSP exerted higher cytotoxicity in macrophage cells compared with submicron-sized silica particles. However, tartrate-resistant acid phosphatase (TRAP) activity and the number of osteoclast cells (TRAP-positive multinucleated cells) were not changed by nSP treatment in the presence of receptor activator of nuclear factor ?B ligand (RANKL) at doses that did not induce cytotoxicity by silica particles. These results indicated that nSP did not cause differentiation of osteoclasts. Collectively, the results suggested that nanosilica exerts no effect on RANKL-induced osteoclast differentiation of RAW264.7 cells, although a detailed mechanistic examination of the nSP70-mediated cytotoxic effect is needed. PMID:21777482

Nabeshi, Hiromi; Yoshikawa, Tomoaki; Akase, Takanori; Yoshida, Tokuyuki; Tochigi, Saeko; Hirai, Toshiro; Uji, Miyuki; Ichihashi, Ko-Ichi; Yamashita, Takuya; Higashisaka, Kazuma; Morishita, Yuki; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-Ichi; Itoh, Norio; Yoshioka, Yasuo; Tsutsumi, Yasuo

2011-01-01

155

Effect of amorphous silica nanoparticles on in vitro RANKL-induced osteoclast differentiation in murine macrophages  

NASA Astrophysics Data System (ADS)

Amorphous silica nanoparticles (nSP) have been used as a polishing agent and/or as a remineralization promoter for teeth in the oral care field. The present study investigates the effects of nSP on osteoclast differentiation and the relationship between particle size and these effects. Our results revealed that nSP exerted higher cytotoxicity in macrophage cells compared with submicron-sized silica particles. However, tartrate-resistant acid phosphatase (TRAP) activity and the number of osteoclast cells (TRAP-positive multinucleated cells) were not changed by nSP treatment in the presence of receptor activator of nuclear factor ?B ligand (RANKL) at doses that did not induce cytotoxicity by silica particles. These results indicated that nSP did not cause differentiation of osteoclasts. Collectively, the results suggested that nanosilica exerts no effect on RANKL-induced osteoclast differentiation of RAW264.7 cells, although a detailed mechanistic examination of the nSP70-mediated cytotoxic effect is needed.

Nabeshi, Hiromi; Yoshikawa, Tomoaki; Akase, Takanori; Yoshida, Tokuyuki; Tochigi, Saeko; Hirai, Toshiro; Uji, Miyuki; Ichihashi, Ko-Ichi; Yamashita, Takuya; Higashisaka, Kazuma; Morishita, Yuki; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-Ichi; Itoh, Norio; Yoshioka, Yasuo; Tsutsumi, Yasuo

2011-07-01

156

Evaluation of pulsed laser ablation in liquids generated gold nanoparticles as novel transfection tools: efficiency and cytotoxicity  

NASA Astrophysics Data System (ADS)

Varying transfection efficiencies and cytotoxicity are crucial aspects in cell manipulation. The utilization of gold nanoparticles (AuNP) has lately attracted special interest to enhance transfection efficiency. Conventional AuNP are usually generated by chemical reactions or gas pyrolysis requiring often cell-toxic stabilizers or coatings to conserve their characteristics. Alternatively, stabilizer- and coating-free, highly pure, colloidal AuNP can be generated by pulsed laser ablation in liquids (PLAL). Mammalian cells were transfected efficiently by addition of PLAL-AuNP, but data systematically evaluating the cell-toxic potential are lacking. Herein, the transfection efficiency and cytotoxicity of PLAL AuNP was evaluated by transfection of a mammalian cell line with a recombinant HMGB1/GFP DNA expression vector. Different methods were compared using two sizes of PLAL-AuNP, commercialized AuNP, two magnetic NP-based protocols and a conventional transfection reagent (FuGENE HD; FHD). PLAL-AuNP were generated using a Spitfire Pro femtosecond laser system delivering 120 fs laser pulses at a wavelength of 800 nm focusing the fs-laser beam on a 99.99% pure gold target placed in ddH2O. Transfection efficiencies were analyzed after 24h using fluorescence microscopy and flow cytometry. Toxicity was assessed measuring cell proliferation and percentage of necrotic, propidium iodide positive cells (PI %). The addition of PLAL-AuNP significantly enhanced transfection efficiencies (FHD: 31 %; PLAL-AuNP size-1: 46 %; size-2: 50 %) with increased PI% but no reduced cell proliferation. Commercial AuNP-transfection showed significantly lower efficiency (23 %), slightly increased PI % and reduced cell proliferation. Magnetic NP based methods were less effective but showing also lowest cytotoxicity. In conclusion, addition of PLAL-AuNP provides a novel tool for transfection efficiency enhancement with acceptable cytotoxic side-effects.

Willenbrock, Saskia; Durán, María. Carolina; Barchanski, Annette; Barcikowski, Stephan; Feige, Karsten; Nolte, Ingo; Murua Escobar, Hugo

2014-03-01

157

Weakly Charged Cationic Nanoparticles Induce DNA Bending and Strand Separation  

SciTech Connect

The understanding of interactions between double stranded (ds) DNA and charged nanoparticles will have a broad bearing on many important applications from drug delivery [ 1 4 ] to DNAtemplated metallization. [ 5 , 6 ] Cationic nanoparticles (NPs) can bind to DNA, a negatively charged molecule, through a combination of electrostatic attraction, groove binding, and intercalation. Such binding events induce changes in the conformation of a DNA strand. In nature, DNA wraps around a cylindrical protein assembly (diameter and height of 6 nm) [ 7 ] with an 220 positive charge, [ 8 ] creating the complex known as chromatin. Wrapping and bending of DNA has also been achieved in the laboratory through the binding of highly charged species such as molecular assemblies, [ 9 , 10 ] cationic dendrimers, [ 11 , 12 ] and nanoparticles. [ 13 15 ] The charge of a nanoparticle plays a crucial role in its ability to induce DNA structural changes. If a nanoparticle has a highly positive surface charge density, the DNA is likely to wrap and bend upon binding to the nanoparticle [ 13 ] (as in the case of chromatin). On the other hand, if a nanoparticle is weakly charged it will not induce dsDNA compaction. [ 9 , 10 , 15 ] Consequently, there is a transition zone from extended to compact DNA conformations which depends on the chemical nature of the nanoparticle and occurs for polycations with charges between 5 and 10. [ 9 ] While the interactions between highly charged NPs and DNA have been extensively studied, the processes that occur within the transition zone are less explored.

Railsback, Justin [North Carolina State University; Singh, Abhishek [North Carolina State University; Pearce, Ryan [North Carolina State University; McKnight, Timothy E [ORNL; Collazo, Ramon [North Carolina State University; Sitar, Zlatko [ORNL; Yingling, Yaroslava [North Carolina State University; Melechko, Anatoli Vasilievich [ORNL

2012-01-01

158

Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells  

SciTech Connect

Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ? Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ? The impairment of mitochondrial functions may contribute to the enhanced toxicity. ? Inhibition of JNK activity attenuated palmitate/ CsA induced toxicity. ? Palmitate sensitizes cells to the toxicity induced by CsA at therapeutic exposure. ? Elevated free fatty acids may predispose the patients to CsA-induced toxicity.

Luo, Yi, E-mail: yi.luo@pfizer.com; Rana, Payal; Will, Yvonne

2012-06-01

159

Mechanism of Menadione-Induced Cytotoxicity in Rat Platelets  

Microsoft Academic Search

The elevation of intracellular Ca2+in various tissue through oxidative stress induced by menadione has been well documented. Increase of Ca2+level in platelets results in aggregation of platelets. To test the hypothesis that menadione-induced Ca2+elevations can play a role in platelet aggregation, we have studied the effect of menadione on aggregation of platelets isolated from female rats. Treatment with menadione to

Kyung-Ah Kim; Joo-Young Lee; Ki-Sook Park; Mee-Jeong Kim; Jin-Ho Chung

1996-01-01

160

Photoexpulsion of Surface-Grafted Ruthenium Complexes and Subsequent Release of Cytotoxic Cargos to Cancer Cells from Mesoporous Silica Nanoparticles  

PubMed Central

Ruthenium(II) polypyridyl complexes have emerged both as promising probes of DNA structure and as anticancer agents because of their unique photophysical and cytotoxic properties. A key consideration in the administration of those therapeutic agents is the optimization of their chemical reactivities to allow facile attack on the target sites, yet avoid unwanted side effects. Here, we present a drug delivery platform technology, obtained by grafting the surface of mesoporous silica nanoparticles (MSNPs) with ruthenium(II) dipyridophenazine (dppz) complexes. This hybrid nanomaterial displays enhanced luminescent properties relative to that of the ruthenium(II) dppz complex in a homogeneous phase. Since the coordination between the ruthenium(II) complex and a monodentate ligand linked covalently to the nanoparticles can be cleaved under irradiation with visible light, the ruthenium complex can be released from the surface of the nanoparticles by selective substitution of this ligand with a water molecule. Indeed, the modified MSNPs undergo rapid cellular uptake, and after activation with light, the release of an aqua ruthenium(II) complex is observed. We have delivered, in combination, the ruthenium(II) complex and paclitaxel, loaded in the mesoporous structure, to breast cancer cells. This hybrid material represents a promising candidate as one of the so-called theranostic agents that possess both diagnostic and therapeutic functions. PMID:23815127

Frasconi, Marco; Liu, Zhichang; Lei, Juying; Wu, Yilei; Strekalova, Elena; Malin, Dmitry; Ambrogio, Michael W.; Chen, Xinqi; Botros, Youssry Y.; Cryns, Vincent L.; Sauvage, Jean-Pierre; Stoddart, J. Fraser

2014-01-01

161

Erythropoietin reduces cisplatin-induced neurotoxicity without impairment of cytotoxic effects against tumor cells.  

PubMed

Cisplatin, a widely used chemotherapeutic is approved for the management of various solid tumors. Administration of cisplatin is associated with induction of significant toxicities that include neurotoxicity and nephrotoxicity, the latter leading to severe and debilitating anemia. Since erythropoietin, a hematopoietic growth factor that corrects chemotherapy-induced anemia, reduces transfusion requirements and seems to improve the patient's quality of life, has been shown to exert cytoprotective effects we decided to investigate its direct influence on cisplatin-induced neurotoxicity against primary cortical neurons isolated from rats. We observed that pre-treatment of neurons with erythropoietin significantly protects these cells from cisplatin-induced cytotoxicity. These effects correlated with amelioration of cisplatin-mediated activation of ERK1/2 kinases and decreased cleavage of caspase 3. Similarly to erythropoietin, a selective ERK1/2 inhibitor significantly reduced cisplatin-induced cytotoxicity against neuronal cells. Importantly, using the same experimental setting we did not observe any protection from cisplatin cytotoxicity against four established tumor cell lines. Altogether our studies confirm that erythropoietin might be an effective cytoprotective agent that reduces cisplatin-induced neurotoxicity. PMID:17982682

Nowis, Dominika; Legat, Magdalena; Bil, Jacek; Kurzaj, Zuzanna; Issat, Tadeusz; Stoklosa, Tomasz; Mioduszewska, Barbara; Kaczmarek, Leszek; Jakóbisiak, Marek; Golab, Jakub

2007-12-01

162

Involvement of intracellular Na^+ accumulation in Hg^{+2} or Cd^{+2} induced cytotoxicity  

NASA Astrophysics Data System (ADS)

Previously we showed that hepatocyte lysis induced by Hg^{+2} or Cd^{+2} could be partly attributed to mitochondrial toxicity [1, 2]. Similar changes in Na^+ homeostasis induced when Cd^{+2} or Hg^{+2} was incubated with hepatocytes. Cd^{+2} or Hg^{+2} induced cytotoxicity were prevented by Na^+ omission from the media or by the addition of the Na^+/H^+ exchange inhibitor 5-(N, N-dimethyl)-amiloride. Furthermore the omission of CI^- from the media or 2 addition of glycine, a CI^- channel blocker also prevented Cd^{+2} or Hg^{+2} induced hepatocyte toxicity. A hypotonic media also increased Cd^{+2} or Hg^{+2} induced hepatocyte cytotoxicity. This suggests that Cd^{+2} or Hg^{+2} cytotoxicity could be partly attributed to disruption of cell volume regulation mechanisms. The increased osmotic load caused by the uncontrolled accumulation of intracellular Na^+ in Cd^{+2} or Hg^{+2} treated hepatocytes likely resulted from the activation of Na^+/H^+ exchanger and the Na^+/HCO3^- cotransporter by the acidosis and ATP depletion caused by mitochondrial toxicity.

Pourahmad, J.; O'Brien, P. J.

2003-05-01

163

Catalponol enhances dopamine biosynthesis and protects against L-DOPA-induced cytotoxicity in PC12 cells.  

PubMed

The effects of catalponol (1) on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Catalponol at concentration ranges of 1-5 microM increased the intracellular levels of dopamine at 12-48 h. Catalponol at concentrations of up to 10 microM did not alter cell viability. Tyrosine hydroxylase (TH) activity was enhanced by 1 at 3 microM in a time-dependent manner, but aromatic L-amino acid decarboxylase activity was not. Catalponol also increased the intracellular levels of cyclic AMP and TH phosphorylation. In addition, catalponol at 3 microM associated with L-DOPA (20-50 microM) further enhanced the increases in dopamine levels induced by L-DOPA (50-100 microM) at 24 h. Catalponol at 2-5 microM inhibited L-DOPA (100-200 microM)-induced cytotoxicity at 48 h. These results suggest that 1 enhanced dopamine biosynthesis by inducing TH activity and protected against L-DOPA-induced cytotoxicity in PC12 cells, which was mediated by the increased levels of cyclic AMP. PMID:20183248

Huang, Hai-Shan; Han, Xiang-Hua; Hwang, Bang-Yeon; Park, Jae-In; Yoo, Se-Kuel; Choi, Hyun-Sook; Lim, Sung-Cil; Lee, Myung-Koo

2009-10-01

164

Cytotoxicity and gene expression changes induced by inorganic and organic trivalent arsenicals in human cells.  

PubMed

Inorganic arsenic (iAs) is a human urinary bladder, skin and lung carcinogen. iAs is metabolized to methylated arsenicals, with trivalent arsenicals more cytotoxic than pentavalent forms in vitro. In this study, cytotoxicity and gene expression changes for arsenite (iAs(III)), monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)) were evaluated in three human cell types, urothelial (1T1), keratinocyte (HEK001) and bronchial epithelial (HBE) cells, corresponding to target organs for iAs-induced cancer. Cells were exposed to arsenicals to determine cytotoxicity and to study gene expression changes. Affymetrix chips were used to determine differentially expressed genes (DEGs) by statistical analysis. Lethal concentrations (LC50) for trivalent arsenicals in all cells ranged from 1.6 to 10?M. MMA(III) and DMA(III) had 4-12-fold greater potency compared to iAs. Increasing concentrations of iAs(III) induced more genes and additional signaling pathways in HBE cells. At equivalent cytotoxic concentrations, greater numbers of DEGs were induced in 1T1 cells compared to the other cells. Each arsenical altered slightly different signaling pathways within and between cell types, but when altered pathways from all three arsenicals were combined, they were similar between cell types. The major signaling pathways altered included NRF2-mediated stress response, interferon, p53, cell cycle regulation and lipid peroxidation. These results show a similar process qualitatively and quantitatively for all three cell types, and support a mode of action involving cytotoxicity and regenerative proliferation. PMID:23876855

Dodmane, Puttappa R; Arnold, Lora L; Kakiuchi-Kiyota, Satoko; Qiu, Fang; Liu, Xiangde; Rennard, Stephen I; Cohen, Samuel M

2013-10-01

165

Flutamide-Induced Cytotoxicity and Oxidative Stress in an In Vitro Rat Hepatocyte System  

PubMed Central

Flutamide (FLU) is a competitive antagonist of the androgen receptor which has been reported to induce severe liver injury in some patients. Several experimental models suggested that an episode of inflammation during drug treatment predisposes animals to tissue injury. The molecular cytotoxic mechanisms of FLU in isolated rat hepatocytes using an in vitro oxidative stress inflammation system were investigated in this study. When a nontoxic hydrogen peroxide (H2O2) generating system (glucose/glucose oxidase) with peroxidase or iron(II) [Fe(II)] (to partly simulate in vivo inflammation) was added to the hepatocytes prior to the addition of FLU, increases in FLU-induced cytotoxicity and lipid peroxidation (LPO) were observed that were decreased by 6-N-propyl-2-thiouracil or deferoxamine, respectively. N-Acetylcysteine decreased FLU-induced cytotoxicity in this system. Potent antioxidants, for example, Trolox ((±)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), resveratrol (3,5,4?-trihydroxy-trans-stilbene), and DPPD (N,N?-diphenyl-1,4-phenylenediamine) also significantly decreased FLU-induced cytotoxicity and LPO and increased mitochondrial membrane potential (MMP) and glutathione (GSH) levels in the H2O2 generating system with peroxidase. TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl), a known reactive oxygen species (ROS) scavenger and superoxide dismutase mimetic, also significantly decreased toxicity caused by FLU in this system. These results raise the possibility that the presence or absence of inflammation may be another susceptibility factor for drug-induced hepatotoxicity. PMID:25371773

Maruf, Abdullah Al; O'Brien, Peter

2014-01-01

166

Capsaicin induces cytotoxicity in pancreatic neuroendocrine tumor cells via mitochondrial action.  

PubMed

Capsaicin (CAP), the pungent ingredient of chili peppers, inhibits growth of various solid cancers via TRPV1 as well as TRPV1-independent mechanisms. Recently, we showed that TRPV1 regulates intracellular calcium level and chromogranin A secretion in pancreatic neuroendocrine tumor (NET) cells. In the present study, we characterize the role of the TRPV1 agonist - CAP - in controlling proliferation and apoptosis of pancreatic BON and QGP-1 NET cells. We demonstrate that CAP reduces viability and proliferation, and stimulates apoptotic death of NET cells. CAP causes mitochondrial membrane potential loss, inhibits ATP synthesis and reduces mitochondrial Bcl-2 protein production. In addition, CAP increases cytochrome c and cleaved caspase 3 levels in cytoplasm. CAP reduces reactive oxygen species (ROS) generation. The antioxidant N-acetyl-l-cysteine (NAC) acts synergistically with CAP to reduce ROS generation, without affecting CAP-induced toxicity. TRPV1 protein reduction by 75% reduction fails to attenuate CAP-induced cytotoxicity. In summary, these results suggest that CAP induces cytotoxicity by disturbing mitochondrial potential, and inhibits ATP synthesis in NET cells. Stimulation of ROS generation by CAP appears to be a secondary effect, not related to CAP-induced cytotoxicity. These results justify further evaluation of CAP in modulating pancreatic NETs in vivo. PMID:24075930

Skrzypski, M; Sassek, M; Abdelmessih, S; Mergler, S; Grötzinger, C; Metzke, D; Wojciechowicz, T; Nowak, K W; Strowski, M Z

2014-01-01

167

Intracellular glutathione regulates Andrographolide-induced cytotoxicity on hepatoma Hep3B cells.  

PubMed

Andrographolide (ANDRO), a diterpenoid lactone isolated from the traditional herbal plant Andrographis paniculata, was reported to induce apoptosis in hepatoma Hep3B cells in our previous study (Ji LL, Liu TY, Liu J, Chen Y, Wang ZT. Andrographolide inhibits human hepatoma-derived Hep3B cells growth through the activation of c-Jun N-terminal kinase. Planta Med 2007; 73: 1397-1401). The present investigation was carried out to observe whether cellular reduced glutathione (GSH) plays important roles in ANDRO-induced apoptosis. ANDRO initially increased intracellular GSH levels which then decreased later, while inhibition of cellular GSH synthesis by L-Buthionine-(S,R)-sulfoximine (BSO) augmented ANDRO-induced cytotoxicity and apoptosis in Hep3B cells. On the other hand, the thiol antioxidant dithiothreitol (DTT) rescued ANDRO-depleted cellular GSH, and abrogated ANDRO-induced cytotoxicity and apoptosis. Furthermore, BSO pretreatment augmented ANDRO-decreased expression of antioxidant protein thioredoxin 1 (Trx1), while DTT reversed this decrease. Further results showed that ANDRO increased the activity of the GSH-related antioxidant enzyme glutathione peroxidase (GPx) and the production of intracellular reactive oxygen species (ROS). Taken together, this study demonstrates that the intracellular redox system plays important roles in regulating the cytotoxicity of ANDRO on hepatoma Hep3B cells. PMID:19695125

Ji, Lili; Shen, Kaikai; Liu, Jun; Chen, Ying; Liu, Tianyu; Wang, Zhengtao

2009-01-01

168

CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (??m), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS. PMID:25018698

Lee, Jae Keun; Hwang, Sang Gil; Shin, Jin Hee; Shim, Jaekyung; Choi, Eui-Ju

2014-01-01

169

The Synthesis of Iron Oxide Nanoparticles via Seed-Mediated Process and its Cytotoxicity Studies  

Microsoft Academic Search

The development of a seed-mediated growth method for synthesis of iron oxide nanoparticles with tunable size distribution\\u000a and magnetic properties is reported. The detailed investigation of the size distribution of seed as well as iron oxide nanoparticles\\u000a during the growth process has been carried out using transmission electron microscopy (TEM). It was observed that the distribution\\u000a of size gradually becomes

J.-H. Huang; H. J. Parab; R. S. Liu; T.-C. Lai; M. Hsiao; C. H. Chen; D.-P. Tsai; Y.-K. Hwu

170

The involvement of cytochrome P4502E1 in 2-bromoethanol-induced hepatocyte cytotoxicity.  

PubMed

The cytotoxicity of 2-bromoethanol towards hepatocytes isolated from rats was concentration-dependent (EC(50)100 mu M, 2 hr). Bromoacetaldehyde was more toxic (EC(50)60 mu M, 2 hr) and bromoacetic acid was less toxic (EC(50)150 mu M, 2 hr). Glutathione (GSH) depletion occurred before cytotoxicity ensued and GSH depleted hepatocytes were more susceptible to 2-bromoethanol. Lipid peroxidation increased steadily 1 hr after 2-bromoethanol addition and antioxidants, iron chelators or hypoxia prevented 2-bromoethanol induced lipid peroxidation and cell lysis. Alcohol dehydrogenase inhibitors, methyl pyrazole or dimethyl sulfoxide only partly prevented 2-bromoethanol induced GSH depletion, lipid peroxidation and cytotoxicity. However, cytochrome P4502E1 (CYP2E1) inhibitors/substrates were more effective at preventing 2-bromoethanol-induced GSH depletion, lipid peroxidation and cytotoxicity suggesting that 2-bromoethanol is mostly metabolically activated by CYP2E1. Also, hepatocytes isolated from CYP2E1 induced rats were more susceptible to 2-bromoethanol and hepatocytes isolated from rats pretreated with carbon disulfide to inactivate CYP2E1 were more resistant to 2-bromoethanol treatment. Formation of S-(formylmethyl)glutathione during 2-bromoethanol metabolism by microsomal mixed function oxidase in the presence of GSH was also prevented by cytochrome P4502E1 inhibitors/substrates or by Anti-Rat CYP2E1. Furthermore, aldehyde dehydrogenase inhibitors-cyanamide or chloral hydrate increased 2-bromoethanol dependent hepatocyte susceptibility. This suggests that 2-bromoethanol is preferably metabolised by CYP2E1 dependent monoxygenase to form 2-bromoacetaldehyde which causes cell lysis as a result of GSH depletion and lipid peroxidation. PMID:8861782

Khan, S; Sood, C; O'Brien, P J

1996-04-01

171

Involvement of mitochondrial pathway in NCTD-induced cytotoxicity in human hepG2 cells  

Microsoft Academic Search

BACKGROUND: Norcantharidin, the demethylated analog of cantharidin derived from a traditional Chinese medicine, Mylabris, has been used in the treatment of anti-cancer effects. However, the detailed mechanisms underlying this process are generally unclear. The aim of this study was to investigate the mechanism of NCTD-induced apoptosis in HepG2 cells. METHODS: The cytotoxicity was measured by MTT assay for cellular viability

Cheng Chang; You-Qing Zhu; Juan-juan Mei; Shi-quan Liu; Jun Luo

2010-01-01

172

Essential role of Nrf2 in protection against hydroquinone- and benzoquinone-induced cytotoxicity  

Microsoft Academic Search

Benzene is a well-established human carcinogen. Benzene metabolites hydroquinone (HQ) and benzoquinone (BQ) are highly reactive molecules capable of producing reactive oxygen species and causing oxidative stress. In this study, we investigated the role of the Nrf2, a key nuclear transcription factor that regulates antioxidant response element (ARE)-containing genes, in defense against HQ- and BQ-induced cytotoxicity in cultured human lung

Valentina Rubio; Jiawei Zhang; Mahara Valverde; Emilio Rojas; Zheng-Zheng Shi

2011-01-01

173

Aneuploidogenic effects and DNA oxidation induced in vitro by differently sized gold nanoparticles  

PubMed Central

Gold nanoparticles (Au NPs) are used in many fields, including biomedical applications; however, no conclusive information on their potential cytotoxicity and genotoxicity mechanisms is available. For this reason, experiments in human primary lymphocytes and murine macrophages (Raw264.7) were performed exposing cells to spherical citrate-capped Au NPs with two different nominal diameters (5 nm and 15 nm). The proliferative activity, mitotic, apoptotic, and necrotic markers, as well as chromosomal damage were assessed by the cytokinesis-block micronucleus cytome assay. Fluorescence in situ hybridization with human and murine pancentromeric probes was applied to distinguish between clastogenic and aneuploidogenic effects. Our results indicate that 5 nm and 15 nm Au NPs are able to inhibit cell proliferation by apoptosis and to induce chromosomal damage, in particular chromosome mis-segregation. DNA strand breaks were detected by comet assay, and the modified protocol using endonuclease-III and formamidopyrimidine-DNA glycosylase restriction enzymes showed that pyrimidines and purines were oxidatively damaged by Au NPs. Moreover, we show a size-independent correlation between the cytotoxicity of Au NPs and their tested mass concentration or absolute number, and genotoxic effects which were more severe for Au NP 15 nm compared to Au NP 5 nm. Results indicate that apoptosis, aneuploidy, and DNA oxidation play a pivotal role in the cytotoxicity and genotoxicity exerted by Au NPs in our cell models. PMID:24855356

Di Bucchianico, Sebastiano; Fabbrizi, Maria Rita; Cirillo, Silvia; Uboldi, Chiara; Gilliland, Douglas; Valsami-Jones, Eugenia; Migliore, Lucia

2014-01-01

174

Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake  

NASA Astrophysics Data System (ADS)

The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

Parab, Harshala J.; Huang, Jing-Hong; Lai, Tsung-Ching; Jan, Yi-Hua; Liu, Ru-Shi; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan; Hwu, Yeu-Kuang; Tsai, Din Ping; Chuang, Shih-Yi; Pang, Jong-Hwei S.

2011-09-01

175

Signaling Pathways Involved in Lunar Dust Induced Cytotoxicity  

NASA Technical Reports Server (NTRS)

The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (< 3 micron), that is respirable. The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust-induced changes of the expression of fibrosis-related genes, and to identify specific signaling pathways involved in lunar dust-induced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.1, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The total RNAs were isolated from the blood or lung tissue after being lavaged, using the Qigen RNeasy kit. The Rat Fibrosis RT2 Profile PCR Array was used to profile the expression of 84 genes relevant to fibrosis. The genes with significant expression changes are identified and the gene expression data were further analyzed using IPA pathway analysis tool to determine the signaling pathways with significant changes.

Zhang, Ye; Lam, Chiu-Wing; Scully, Robert R.; Williams, Kyle; Zalesak, Selina; Wu, Honglu; James, John T.

2014-01-01

176

Rapid green synthesis of silver nanoparticles from Chrysanthemum indicum L and its antibacterial and cytotoxic effects: an in vitro study  

PubMed Central

The present work reports a simple, cost-effective, and ecofriendly method for the synthesis of silver nanoparticles (AgNPs) using Chrysanthemum indicum and its antibacterial and cytotoxic effects. The formation of AgNPs was confirmed by color change, and it was further characterized by ultraviolet–visible spectroscopy (435 nm). The phytochemical screening of C. indicum revealed the presence of flavonoids, terpenoids, and glycosides, suggesting that these compounds act as reducing and stabilizing agents. The crystalline nature of the synthesized particles was confirmed by X-ray diffraction, as they exhibited face-centered cubic symmetry. The size and morphology of the particles were characterized by transmission electron microscopy, which showed spherical shapes and sizes that ranged between 37.71–71.99 nm. Energy-dispersive X-ray spectroscopy documented the presence of silver. The antimicrobial effect of the synthesized AgNPs revealed a significant effect against the bacteria Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Additionally, cytotoxic assays showed no toxicity of AgNPs toward 3T3 mouse embryo fibroblast cells (25 ?g/mL); hence, these particles were safe to use. PMID:24426782

Arokiyaraj, Selvaraj; Arasu, Mariadhas Valan; Vincent, Savariar; Prakash, Nyayirukannaian Udaya; Choi, Seong Ho; Oh, Young-Kyoon; Choi, Ki Choon; Kim, Kyoung Hoon

2014-01-01

177

Baicalin prevents cadmium induced hepatic cytotoxicity, oxidative stress and histomorphometric alterations.  

PubMed

Therapeutic potential of baicalin was evaluated against Cd-induced hepatic cytotoxicity and oxidative stress. Exposure to Cd (cadmium chloride) in Chang liver cell culture produced cytotoxicity in terms of increase in cell growth inhibition rate, alanine aminotransferase, lactate dehydrogenase, and cellular lipid peroxidation, which was significantly mitigated by baicalin in a concentration dependent manner. Acute exposure to Cd (6.5 mg/kg body weight; ip once only) produced a condition of oxidative stress in rats and substantially increased LPO and GSSG level along with corresponding decrease in GSH and various antioxidant enzymes in liver and also increased the leakage of liver marker enzymes in serum. Therapy with baicalin after 3 h of Cd administration inhibited LPO and formation of GSSG along with increase in liver GSH level. Release of serum transaminases, alkaline phosphatase and lactate dehydrogenase were significantly restored towards control after baicalin treatment. Administration of baicalin helped in restoring the activities of antioxidants enzymes, i.e., superoxide dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase towards control. Histomorphometric analysis also supported biochemical findings of the study. The observations clearly demonstrated that baicalin treatment ameliorated Cd induced hepatic cytotoxicity and oxidative stress and provides evidence for its therapeutic potential against Cd induced oxidative stress. PMID:21924596

Wen, Yi-Fei; Zhao, Jun-Quan; Bhadauria, Monika; Nirala, Satendra Kumar

2013-01-01

178

Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines.  

PubMed

Seventeen steviol derivatives, i.e., 2-18, and 19 isosteviol derivatives, i.e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i.e., 5-9 and 11-14, and five isosteviol derivatives, i.e., 28-32, exhibited activities with single-digit micromolar IC(50) values against one or more cell lines. All of these active compounds possess C(19)-O-acyl group, and among which, ent-kaur-16-ene-13,19-diol 19-O-4',4',4'-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC(50) values in the range of 1.2-4.1 ?M. Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis. These results suggested that acylation of the 19-OH group of kaurane- and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity. PMID:23418165

Ukiya, Motohiko; Sawada, Shingo; Kikuchi, Takashi; Kushi, Yasunori; Fukatsu, Makoto; Akihisa, Toshihiro

2013-02-01

179

Rhododendrol, a depigmentation-inducing phenolic compound, exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism.  

PubMed

Rhododendrol, an inhibitor of melanin synthesis developed for lightening/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase-3 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase-dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity. PMID:24890809

Sasaki, Minoru; Kondo, Masatoshi; Sato, Kohji; Umeda, Mai; Kawabata, Keigo; Takahashi, Yoshito; Suzuki, Tamio; Matsunaga, Kayoko; Inoue, Shintaro

2014-09-01

180

Nickel oxide nanoparticles induce inflammation and genotoxic effect in lung epithelial cells.  

PubMed

Nickel oxide nanoparticles (NiONPs) toxicity has been evaluated in the human pulmonary epithelial cell lines: BEAS-2B and A549. The nanoparticles, used at the doses of 20, 40, 60, 80, 100 ?g/ml, induced a significant reduction of cell viability and an increase of apoptotic and necrotic cells at 24h. A significant release of interleukin-6 and -8 was assessed after 24h of treatment, even intracellular ROS increased already at 45 min after exposure. The results obtained evidenced that the cytokines release was dependent on mitogen activated protein kinases (MAPK) cascade through the induction of NF-kB pathway. NiONPs induced cell cycle alteration in both the cell lines even in different phases and these modifications may be induced by the NPs genotoxic effect, suggested by the nuclear translocation of phospho-ATM and phospho-ATR. Our results confirm the cytotoxic and pro-inflammatory potential of NiONPs. Moreover their ability in inducing DNA damage responses has been demonstrated. Such effects were present in A549 cells which internalize the NPs and BEAS-2B cells in which endocytosis has not been observed. PMID:24503009

Capasso, Laura; Camatini, Marina; Gualtieri, Maurizio

2014-04-01

181

Cytotoxicity, oxidative stress and expression of adhesion molecules in human umbilical vein endothelial cells exposed to dust from paints with or without nanoparticles.  

PubMed

Nanoparticles in primary form and nanoproducts might elicit different toxicological responses. We compared paint-related nanoparticles with respect to effects on endothelial oxidative stress, cytotoxicity and cell adhesion molecule expression. Primary human umbilical vein endothelial cells were exposed to primary nanoparticles (fine, photocatalytic or nanosized TiO(2), aluminium silicate, carbon black, nano-silicasol or axilate) and dust from sanding reference- or nanoparticle-containing paints. Most of the samples increased cell surface expressions of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), but paint sanding dust samples generally generated less response than primary particles of TiO(2) and carbon black. We found no relationship between the expression of adhesion molecules, cytotoxicity and production of reactive oxygen species. In conclusion, sanding dust from nanoparticle-containing paint did not generate more oxidative stress or expression of cell adhesion molecules than sanding dust from paint without nanoparticles, whereas the primary particles had the largest effect on mass basis. PMID:22263546

Mikkelsen, Lone; Jensen, Keld A; Koponen, Ismo K; Saber, Anne T; Wallin, Håkan; Loft, Steffen; Vogel, Ulla; Møller, Peter

2013-03-01

182

Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence  

SciTech Connect

Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS. Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo. We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation. We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN. A 51Cr release assay was used to measure EC damage. Further, we investigated PMN function in response to TNF by measuring chemiluminescence. Agents that attenuate EC damage and PMN activation were evaluated in the above assays. Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury. Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05). Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN. Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05). We conclude that TNF causes EC damage and PMN increase this damage. Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN. In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence. Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.

Zheng, H.; Crowley, J.J.; Chan, J.C.; Hoffmann, H.; Hatherill, J.R.; Ishizaka, A.; Raffin, T.A. (Stanford Univ. Medical Center, CA (USA))

1990-11-01

183

Spontaneous and induced emission in dielectric nanoparticles  

Microsoft Academic Search

An analytical expression is proposed for the rate of radiative decay of excitations of optical centers in an ellipsoidal nanoparticle\\u000a that is considerably smaller than the light wavelength (a, b, c ? ?) and is embedded in the surrounding medium. This expression is compared with the corresponding expression for a bulk crystal.\\u000a The time of radiative decay in nanoparticles spherical

T. T. Basiev; Yu. V. Orlovskii; K. K. Pukhov

2008-01-01

184

Cationic Antimicrobial Peptides and Biogenic Silver Nanoparticles Kill Mycobacteria without Eliciting DNA Damage and Cytotoxicity in Mouse Macrophages  

PubMed Central

With the emergence of multidrug-resistant mycobacterial strains, better therapeutic strategies are required for the successful treatment of the infection. Although antimicrobial peptides (AMPs) and silver nanoparticles (AgNPs) are becoming one of the popular antibacterial agents, their antimycobacterial potential is not fully evaluated. In this study, we synthesized biogenic-silver nanoparticles using bacterial, fungal, and plant biomasses and analyzed their antibacterial activities in combination with AMPs against mycobacteria. Mycobacterium smegmatis was found to be more susceptible to AgNPs compared to M. marinum. We found that NK-2 showed enhanced killing effect with NP-1 and NP-2 biogenic nanoparticles at a 0.5-ppm concentration, whereas LLKKK-18 showed antibacterial activity only with NP-2 at 0.5-ppm dose against M. smegmatis. In case of M. marinum NK-2 did not show any additive activity with NP-1 and NP-2 and LLKKK-18 alone completely inhibited the bacterial growth. Both NP-1 and NP-2 also showed increased killing of M. smegmatis in combination with the antituberculosis drug rifampin. The sizes and shapes of the AgNPs were determined by transmission electron microscopy and dynamic light scattering. AgNPs showed no cytotoxic or DNA damage effects on macrophages at the mycobactericidal dose, whereas treatment with higher doses of AgNPs caused toxicity and micronuclei formation in cytokinesis blocked cells. Macrophages actively endocytosed fluorescein isothiocyanate-labeled AgNPs resulting in nitric oxide independent intracellular killing of M. smegmatis. Apoptosis and cell cycle studies showed that treatment with higher dose of AgNPs arrested macrophages at the G1-phase. In summary, our data suggest the combined effect of biogenic-AgNPs and antimicrobial peptides as a promising antimycobacterial template. PMID:23689720

Mohanty, Soumitra; Jena, Prajna; Mehta, Ranjit; Pati, Rashmirekha; Banerjee, Birendranath; Patil, Satish

2013-01-01

185

Protective effect of kombucha mushroom (KM) tea on phenol-induced cytotoxicity in albino mice.  

PubMed

The present study was carried out to evaluate the protective role of kombucha mushroom (KM) tea on cytotoxicity induced by phenol (PHE) in mice. We used weight gain and micronucleus (MN) frequency as indicators of cytotoxicity and supported these parameters with pathological findings. The animals were randomly divided into seven groups: (Group I) only tap water (Group II) 1000 microl kg(-1) b. wt KM-tea, (Group III) 35 mg kg(-1) body wt. PHE (Group IV) 35 mg kg(-1) body wt. PHE + 250 microl kg(-1) b. wt KM-tea (Group V) 35 mg kg(-1) b. wt PHE + 500 microl kg(-1) b. wt KM-tea (Group VI) 35 mg kg(-1) b. wt PHE + 750 microl kg(-1) b. wt KM-tea, (Group VII) 35 mg kg(-1) b. wt PHE + 1000 microl kg(-1) b. wt KM-tea, for 20 consecutive days by oral gavage. The results indicated that all KM-tea supplemented mice showed a lower MN frequency than erythrocytes in only PHE-treated group. There was an observable regression on account of lesions in tissues of mice supplemented with different doses of KM-tea in histopathological observations. In conclusion, the KM-tea supplementation decreases cytotoxicity induced by PHE and its protective role is dose-dependent. PMID:21387911

Yapar, Kursad; Cavusoglu, Kultigin; Oruc, Ertan; Yalcin, Emine

2010-09-01

186

Zinc at Sub-Cytotoxic Concentrations Induces Heme Oxygenase-1 Expression in Human Cancer Cells  

PubMed Central

Background/Aims This study investigated the effects of zinc on heme oxygenase-1 (HO-1) expression in human cancer cells. Methods/Results Zinc at sub-cytotoxic concentrations (50–100 µM) induces HO-1 expression in the MDA-MB-231 (human breast cancer) and A2780 (human ovarian cancer) cell lines in a concentration- and time-dependent manner. The induction of HO-1 by zinc was detected after 4–6 hours of treatment, reached maximal level at 8 hours, and declined thereafter. Using a human HO-1 gene promoter reporter construct, we identified two antioxidant response elements (AREs) that mediated the zinc-induced increase in HO-1 gene transcription, indicating that the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway is involved in this event. This assumption was supported by the observations that knockdown of Nrf2 expression compromised the zinc-induced increase in HO-1 gene transcription, and that zinc increased Nrf2 protein expression and the Nrf2 binding to the AREs. Additionally, we found that the zinc-induced HO-1 gene transcription can be enhanced by clioquinol, a zinc ionophore, and reversed by pretreatment with TPEN, a known zinc chelator, indicating that an increase in intracellular zinc levels is responsible for this induction. Conclusion These findings demonstrate that zinc at sub-cytotoxic concentrations induces HO-1 expression in human cancer cells. The biological significance of this induction merits further investigation. PMID:23868099

Xue, Jing; Wang, Shuai; Wu, Jinchang; Hannafon, Bethany N.; Ding, Wei-Qun

2013-01-01

187

Copper Oxide Nanoparticles Induced Mitochondria Mediated Apoptosis in Human Hepatocarcinoma Cells  

PubMed Central

Copper oxide nanoparticles (CuO NPs) are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking. We explored the possible mechanisms of apoptosis induced by CuO NPs in human hepatocellular carcinoma HepG2 cells. Prepared CuO NPs were spherical in shape with a smooth surface and had an average diameter of 22 nm. CuO NPs (concentration range 2–50 µg/ml) were found to induce cytotoxicity in HepG2 cells in dose-dependent manner, which was likely to be mediated through reactive oxygen species generation and oxidative stress. Tumor suppressor gene p53 and apoptotic gene caspase-3 were up-regulated due to CuO NPs exposure. Decrease in mitochondrial membrane potential with a concomitant increase in the gene expression of bax/bcl2 ratio suggested that mitochondria mediated pathway involved in CuO NPs induced apoptosis. This study has provided valuable insights into the possible mechanism of apoptosis caused by CuO NPs at in vitro level. Underlying mechanism(s) of apoptosis due to CuO NPs exposure should be further invested at in vivo level. PMID:23940521

Siddiqui, Maqsood A.; Alhadlaq, Hisham A.; Ahmad, Javed; Al-Khedhairy, Abdulaziz A.; Musarrat, Javed; Ahamed, Maqusood

2013-01-01

188

Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment.  

PubMed

Development of nanotechnology calls for a comprehensive understanding of the impact of nanomaterials on biological systems. Autophagy is a lysosome-based degradative pathway which plays an essential role in maintaining cellular homeostasis. Previous studies have shown that nanoparticles from various sources can induce autophagosome accumulation in treated cells. However, the underlying mechanism is still not clear. Gold nanoparticles (AuNPs) are one of the most widely used nanomaterials and have been reported to induce autophagosome accumulation. In this study, we found that AuNPs can be taken into cells through endocytosis in a size-dependent manner. The internalized AuNPs eventually accumulate in lysosomes and cause impairment of lysosome degradation capacity through alkalinization of lysosomal pH. Consistent with previous studies, we found that AuNP treatment can induce autophagosome accumulation and processing of LC3, an autophagosome marker protein. However, degradation of the autophagy substrate p62 is blocked in AuNP-treated cells, which indicates that autophagosome accumulation results from blockade of autophagy flux, rather than induction of autophagy. Our data clarify the mechanism by which AuNPs induce autophagosome accumulation and reveal the effect of AuNPs on lysosomes. This work is significant to nanoparticle research because it illustrates how nanoparticles can potentially interrupt the autophagic pathway and has important implications for biomedical applications of nanoparticles. PMID:21974862

Ma, Xiaowei; Wu, Yanyang; Jin, Shubin; Tian, Yuan; Zhang, Xiaoning; Zhao, Yuliang; Yu, Li; Liang, Xing-Jie

2011-11-22

189

A Signaling Network Induced by ?2 Integrin Controls the Polarization of Lytic Granulesin Cytotoxic Cells  

PubMed Central

Cytotoxic lymphocyte skill target cells by polarized release of the content of perforin-containing granules. In natural killer cells, the binding of ?2 integrin to its ligand ICAM-1 is sufficient to promote not only adhesion but also lytic granule polarization. This provided a unique opportunity to study polarization in the absence of degranulation, and ?2 integrin signaling independently of inside-out signals from other receptors. Using an unbiased proteomics approach we identified a signaling network centered on an integrin-linked kinase (ILK)–Pyk2–Paxillin core that was required for granule polarization. Downstream of ILK, the highly conserved Cdc42–Par6 signaling pathway that controls cell polarity was activated and required for granule polarization. These results delineate two connected signaling networks induced upon ?2 integrin engagement alone, which are integrated to control polarization of the microtubule organizing center and associated lytic granules toward the site of contact with target cells during cellular cytotoxicity. PMID:25292215

Zhang, Minggang; March, Michael E.; Lane, William S.; Long, Eric O.

2014-01-01

190

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma.  

PubMed

The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1?, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity. PMID:25016296

Syed, Deeba N; Lall, Rahul K; Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

2014-12-01

191

Magnetic and Cytotoxicity Properties of La 1? x Sr x MnO 3 (0 ?  x  ? 0.5) Nanoparticles Prepared by a Simple Thermal Hydro-Decomposition  

Microsoft Academic Search

This study reports the magnetic and cytotoxicity properties of magnetic nanoparticles of La1?x\\u000a Sr\\u000a x\\u000a MnO3 (LSMO) with x = 0, 0.1, 0.2, 0.3, 0.4, and 0.5 by a simple thermal decomposition method by using acetate salts of La, Sr, and Mn as starting\\u000a materials in aqueous solution. To obtain the LSMO nanoparticles, thermal decomposition of the precursor was carried out at

Sujittra Daengsakul; Chunpen Thomas; Ian Thomas; Charusporn Mongkolkachit; Sineenat Siri; Vittaya Amornkitbamrung; Santi Maensiri

2009-01-01

192

Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells  

PubMed Central

Background The objective of this study was to evaluate the synthesis and biocompatibility of Fe3O4 nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells. Methods Magnetic Fe3O4 nanoparticles were prepared using a coprecipitation method. The appearance, structure, phase composition, functional groups, surface charge, magnetic susceptibility, and release in vitro were characterized by transmission electron microscopy, x-ray diffraction, scanning electron microscopy-energy dispersive x-ray spectroscopy, and a vibrating sample magnetometer. Blood toxicity, in vitro toxicity, and genotoxicity were investigated. Therapeutic effects were evaluated by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] and flow cytometry assays. Results Transmission electron microscopy revealed that the shapes of the Fe3O4 nanoparticles were approximately spherical, with diameters of about 26.1 ± 5.2 nm. Only the spinel phase was indicated in a comparison of the x-ray diffraction data with Joint Corporation of Powder Diffraction Standards (JCPDS) X-ray powder diffraction files. The O-to-Fe ratio of the Fe3O4 was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe3O4. The vibrating sample magnetometer hysteresis loop suggested that the Fe3O4 nanoparticles were superparamagnetic at room temperature. MTT experiments showed that the toxicity of the material in mouse fibroblast (L-929) cell lines was between Grade 0 to Grade 1, and that the material lacked hemolysis activity. The acute toxicity (LD50) was 8.39 g/kg. Micronucleus testing showed no genotoxic effects. Pathomorphology and blood biochemistry testing demonstrated that the Fe3O4 nanoparticles had no effect on the main organs and blood biochemistry in a rabbit model. MTT and flow cytometry assays revealed that Fe3O4 nano magnetofluid thermotherapy inhibited MCF-7 cell proliferation, and its inhibitory effect was dose-dependent according to the Fe3O4 nano magnetofluid concentration. Conclusion The Fe3O4 nanoparticles prepared in this study have good biocompatibility and are suitable for further application in tumor hyperthermia. PMID:23028225

Chen, Daozhen; Tang, Qiusha; Li, Xiangdong; Zhou, Xiaojin; Zang, Jia; Xue, Wen-qun; Xiang, Jing-ying; Guo, Cai-qin

2012-01-01

193

Effects of the iron-chelating agent deferoxamine on triethylene glycol dimethacrylate, 2-hydroxylethyl methacrylate, hydrogen peroxide-induced cytotoxicity.  

PubMed

Triethylene glycol dimethacrylate (TEGDMA) and 2-hydroxylethyl methacrylate (HEMA) are known to deplete glutathione in mammalian cells, generate reactive oxygen species (ROS), and cause oxidative stress. In this study, we investigated whether hydroxyl radicals (·OH), the most lethal and genotoxic ROS, and the Fenton reaction are involved in the cytotoxicity of resin monomers to four different cell types, namely MC3T3-E1 preosteoblasts, human dental pulp cells (HDPCs), human gingival fibroblasts, and L929 mouse fibroblasts. Deferoxamine (DFO), an iron chelating agent, effectively protected MC3T3-E1 cells from resin monomer-induced cytotoxicity, indicating that cytotoxicity was caused primarily by hydroxyl radicals. However, DFO only had a protective effect against relatively high concentrations of TEGDMA and HEMA in HDPCs and human gingival fibroblasts, and resin monomer-induced cytotoxicity in L929 was not attenuated by DFO. A labile iron pool (LIP) was detectable only in MC3T3-E1 cells among the four cell types. This indicates that the generation of hydroxyl radicals induced by resin monomers is likely dependent on LIP levels. In contrast to resin monomers, hydrogen peroxide (H(2)O(2))-induced cytotoxicity was not prevented by DFO in any of the cell types examined, although hydroxyl radicals were detected in MC3T3-E1 cells and HDPCs on exposure to exogenous H(2)O(2). This result suggests that generation of hydroxyl radicals is not always the primary cause of cytotoxicity in H(2)O(2)-treated cells. PMID:22102427

Zhu, Tingting; Lim, Bum-Soon; Park, Hee Chul; Son, Kyung Mi; Yang, Hyeong-Cheol

2012-01-01

194

Amoebicidal activity of phytosynthesized silver nanoparticles and their in vitro cytotoxicity to human cells.  

PubMed

Acanthamoeba causes infections in humans and other animals and it is important to develop treatment therapies. Jatropha curcas, Jatropha gossypifolia and Euphorbia milii plant extracts synthesized stable silver nanoparticles (AgNPs) that were relatively stable. Amoebicidal activity of J. gossypifolia, J. curcas and E. milii leaf extracts showed little effect on viability of Acanthamoeba castellanii trophozoites. Plant-synthesized AgNPs showed higher amoebicidal activity. AgNPs synthesized by J. gossypifolia extract were able to kill 74-27% of the trophozoites at concentrations of 25-1.56 ?g mL(-1) . AgNPs were nontoxic at minimum inhibitory concentration with peripheral blood mononuclear cells. These results suggest biologically synthesized nanoparticles as an alternative candidate for treatment of Acanthamoeba infections. PMID:23746354

Borase, Hemant P; Patil, Chandrashekhar D; Sauter, Ismael P; Rott, Marilise B; Patil, Satish V

2013-08-01

195

Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549  

Microsoft Academic Search

Nanomaterials, especially silver nanoparticles (Ag NPs), are used in a rapidly increasing number of commercial products. Accordingly,\\u000a the hazards associated with human exposure to nanomaterials should be investigated to facilitate the risk assessment process.\\u000a A potential route of exposure to NPs is through the respiratory system. In the present study, we investigated the effects\\u000a of well-characterized PVP-coated Ag NPs and

Rasmus Foldbjerg; Duy Anh Dang; Herman Autrup

2011-01-01

196

Cytotoxic effect of Green synthesized silver nanoparticles using Melia azedarach against in vitro HeLa cell lines and lymphoma mice model  

Microsoft Academic Search

This communication explains the biosynthesis of stable silver nanoparticles (AgNPs) from Melia azedarach and its cytotoxicity against in vitro HeLa cells and in vivo Dalton's ascites Lymphoma (DAL) mice model. The AgNPs synthesis was determined by UV- visible spectrum and it was further characterized by Scanning Electron Microscopy (SEM), Dynamic light Scattering (DLS) and X-Ray Diffraction (XRD) analysis. Zeta potential

Raman Sukirtha; Kandula Manasa Priyanka; Jacob Joe Antony; Soundararajan Kamalakkannan; Thangam Ramar; Gunasekaran Palani; Muthukalingan Krishnan; Shanmugam Achiraman

197

Demonstration of Cytotoxic Antibodies in Rabbits Bearing Tumors Induced by Shope Fibroma Virus  

PubMed Central

The 51Cr-release test was used to detect cytotoxic antibodies in adult rabbits bearing tumors induced by Shope fibroma virus. The following are the recommended experimental conditions: the infection of RK-13 cells with a multiplicity of 1 to 2 infectious units per cell for 48 hr, 51Cr labeling of infected cells during the last 12 hr of incubation, sensitization of suspended labeled infected cells for 1 hr with immune serum, and quantitation of cell damage by the amount of 51Cr released after 6 hr of incubation in the presence of complement. The immune sera reacted only with fibroma virus-infected cells but not with cells infected with vaccinia virus or herpesvirus type 1. Similarly, sera prepared against vaccinia virus and herpesvirus type 1 were not cytotoxic to fibroma virus-infected cells, although they were cytotoxic to cells infected with homologous viruses. The total antibody activity in sera of rabbits infected with Shope fibroma virus was detected first on day 7, gradually rose to its peak by day 23, and persisted at that level for at least 50 days. The 19S antibody was detected on day 7, reached peak titers by day 13, and disappeared by day 17. The 7S antibody was barely detectable on day 7, reached maximum titers on day 13, and remained high for at least 50 days. The tumors appeared on the 3rd day after virus inoculation, reached maximum size on day 13, and regressed completely by day 23. PMID:4344218

Singh, S. B.; Smith, J. W.; Rawls, W. E.; Tevethia, S. S.

1972-01-01

198

Evaluation of the antimicrobial activity and cytotoxicity of phytogenic gold nanoparticles  

NASA Astrophysics Data System (ADS)

Among the nanoscale materials, noble metal nanoparticles have been attracting the scientific community due to their unique properties and selectivity in biological applications. In the present investigation, gold nanoparticles (AuNPs) were synthesized using rhizome extract of Dioscorea batatas through a simple, clean, inexpensive and eco-friendly method. Treating 1 mM chloroauric acid (HAuCl4) with the rhizome extract at 50 °C resulted in the formation of AuNPs. The reduction of AuNPs was observed by the color change of the solution from colorless to dark red wine. The synthesized nanoparticles were characterized using the techniques UV-Vis spectrophotometers, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. Green synthesized AuNPs were found to be toxic against gram-positive and gram-negative bacteria in liquid media. MTT (dimethyl thiazolyl diphenyl tetrazolium salt) assay showed 21.5 % cell inhibition in lower concentration (0.2 mM) and >50 % cell inhibition after 48 h exposure at higher concentrations (0.8-1 mM).

Sreekanth, T. V. M.; Nagajyothi, P. C.; Supraja, N.; Prasad, T. N. V. K. V.

2014-09-01

199

Inflammatory and cytotoxic responses of an alveolar-capillary coculture model to silica nanoparticles: Comparison with conventional monocultures  

PubMed Central

Background To date silica nanoparticles (SNPs) play an important role in modern technology and nanomedicine. SNPs are present in various materials (tyres, electrical and thermal insulation material, photovoltaic facilities). They are also used in products that are directly exposed to humans such as cosmetics or toothpaste. For that reason it is of great concern to evaluate the possible hazards of these engineered particles for human health. Attention should primarily be focussed on SNP effects on biological barriers. Accidentally released SNP could, for example, encounter the alveolar-capillary barrier by inhalation. In this study we examined the inflammatory and cytotoxic responses of monodisperse amorphous silica nanoparticles (aSNPs) of 30 nm in size on an in vitro coculture model mimicking the alveolar-capillary barrier and compared these to conventional monocultures. Methods Thus, the epithelial cell line, H441, and the endothelial cell line, ISO-HAS-1, were used in monoculture and in coculture on opposite sides of a filter membrane. Cytotoxicity was evaluated by the MTS assay, detection of membrane integrity (LDH release), and TER (Transepithelial Electrical Resistance) measurement. Additionally, parameters of inflammation (sICAM-1, IL-6 and IL-8 release) and apoptosis markers were investigated. Results Regarding toxic effects (viability, membrane integrity, TER) the coculture model was less sensitive to apical aSNP exposure than the conventional monocultures of the appropriate cells. On the other hand, the in vitro coculture model responded with the release of inflammatory markers in a much more sensitive fashion than the conventional monoculture. At concentrations that were 10-100fold less than the toxic concentrations the apically exposed coculture showed a release of IL-6 and IL-8 to the basolateral side. This may mimic the early inflammatory events that take place in the pulmonary alveoli after aSNP inhalation. Furthermore, a number of apoptosis markers belonging to the intrinsic pathway were upregulated in the coculture following aSNP treatment. Analysis of the individual markers indicated that the cells suffered from DNA damage, hypoxia and ER-stress. Conclusion We present evidence that our in vitro coculture model of the alveolar-capillary barrier is clearly advantageous compared to conventional monocultures in evaluating the extent of damage caused by hazardous material encountering the principle biological barrier in the lower respiratory tract. PMID:21272353

2011-01-01

200

Surface Charges and Shell Crosslinks Each Play Significant Roles in Mediating Degradation, Biofouling, Cytotoxicity and Immunotoxicity for Polyphosphoester-based Nanoparticles  

PubMed Central

The construction of nanostructures from biodegradable precursors and shell/core crosslinking have been pursued as strategies to solve the problems of toxicity and limited stability, respectively. Polyphosphoester (PPE)-based micelles and crosslinked nanoparticles with non-ionic, anionic, cationic, and zwitterionic surface characteristics for potential packaging and delivery of therapeutic and diagnostic agents, were constructed using a quick and efficient synthetic strategy, and importantly, demonstrated remarkable differences in terms of cytotoxicity, immunotoxicity, and biofouling properties, as a function of their surface characteristics and also with dependence on crosslinking throughout the shell layers. For instance, crosslinking of zwitterionic micelles significantly reduced the immunotoxicity, as evidenced from the absence of secretions of any of the 23 measured cytokines from RAW 264.7 mouse macrophages treated with the nanoparticles. The micelles and their crosslinked analogs demonstrated lower cytotoxicity than several commercially-available vehicles, and their degradation products were not cytotoxic to cells at the range of the tested concentrations. PPE-nanoparticles are expected to have broad implications in clinical nanomedicine as alternative vehicles to those involved in several of the currently available medications. PMID:24264796

Elsabahy, Mahmoud; Zhang, Shiyi; Zhang, Fuwu; Deng, Zhou J.; Lim, Young H.; Wang, Hai; Parsamian, Perouza; Hammond, Paula T.; Wooley, Karen L.

2013-01-01

201

Human gammadelta T lymphocytes exert natural and IL-2-induced cytotoxicity to neuroblastoma cells.  

PubMed

Human gammadelta T lymphocytes play an important role in nonadaptive reactions to infection and early tumor defense. This is the first report that freshly isolated, native gammadelta T cells of some healthy donors can kill human neuroblastoma cells to varying degrees. Their killing ability was increased and maintained during expansion and cultivation with interleukin-2 (IL-2; 400 IU/mL) for as long as 30 days (100% specific lysis at an effector-to-target cell (E:T) ratio of 20:1). gammadelta T lymphocytes without this spontaneous killing ability gained a specific cytolytic activity of 81% +/- 10.4% SD after stimulation with IL-2 for 24 hours. gammadelta cells were isolated from peripheral blood by positive enrichment (using a magnetic cell sorting system; purity, 95.2% +/- 3.2% SD, n = 21). High natural cytotoxic activity against human neuroblastoma cell lines (>50% specific lysis at an E:T ratio of 20:1) was exhibited by one of 11 donors, whereas two of 11 showed medium cytotoxicity (30% to 50% specific lysis). Eight of 11 donors showed very slight or no lytic activity against human neuroblastoma cells (<30% specific lysis). gammadelta T cells were also cytotoxic against Daudi (32.7% specific lysis at an E:T ratio of 20:1), Raji (10.3%), Colo 205 (23.1%), A 204 (54%), K 562 (100%), and SK-N-MC (100%) cells. Isolated gammadelta T cells were grown in Iscove modified Dulbecco medium with IL-2 (400 IU/mL). Increased cell proliferation (38.5% to 182%) was induced with phytohemagglutinin, IL-15, Clodronat, OKT3, or various combinations of these. Results of cold target inhibition assays suggest a natural killer-like activity of the gammadelta T-cell killing mechanism. Peptidase or papain render neuroblastoma cells unsusceptible to gammadelta T-cell killing, suggesting the involvement of antigen peptide(s) in the process of neuroblastoma cell killing. Treatment with acid phosphatase reduced specific lysis by 66.5% +/- 34.1% SD, which suggests a binding to phosphorylated neuroblastoma cell-surface structures in the killing mechanism of gammadelta T cells. Heat shock did not affect the extent of neuroblastoma killing by gammadelta cells. Recognition of neuroblastoma cells by gammadelta cytotoxic T lymphocytes is negatively regulated by major histocompatibility complex I receptors. Evidence for natural and inducible cell cytotoxicity of gammadelta T cells against human neuroblastoma cells, easy propagation, purification, and missing alloreactivity in mixed lymphocytes cultures indicates a role for this subpopulation of T lymphocytes in adoptive immunotherapy. PMID:11001547

Schilbach, K E; Geiselhart, A; Wessels, J T; Niethammer, D; Handgretinger, R

2000-01-01

202

Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer specific cytotoxicity and tumor growth delay  

PubMed Central

Purpose Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment and novel therapies are therefore in high demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug Experimental design The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter Insulinoma-associated 1 (INSM1). Therapeutic effect was evaluated in vitro in SCLC cell lines and in vivo in SCLC xenografted nude mice using the non-viral nanoparticle, DOTAP:Cholesterol for transgene delivery. Results INSM1-YCD/5-FC and INSM1-YCD-YUPRT/5-FC therapy induced high cytotoxicity in a range of SCLC cell lines. The highest therapeutic effect was obtained from the YCD-YUPRT fusion gene strategy. No cytotoxicity was induced after treatment of cell lines of other origin than SCLC. In addition the INSM1-YCD-YUPRT/5-FC therapy was superior to an established suicide gene system consisting of the Herpes Simplex Virus Thymidine Kinase (HSVTK) gene and prodrug Ganciclovir (GCV). The superior effect was in part due to massive bystander cytotoxicity of YCD-YUPRT-produced toxins. Finally, INSM1-YCD-YUPRT/5-FC therapy induced significant tumor growth delay in SCLC xenografts compared to control treated xenografts. Conclusions The current study is the first to test cytosine deaminase-based suicide gene therapy for SCLC and the first to demonstrate an anti-tumor effect from the delivery of suicide gene therapeutics for SCLC in vivo. PMID:20371678

Christensen, Camilla L.; Gjetting, Torben; Poulsen, Thomas T.; Cramer, Frederik; Roth, Jack A.; Poulsen, Hans S.

2012-01-01

203

Protective effect of ebselen against hydrogen peroxide-induced cytotoxicity and DNA damage in HepG 2 cells  

Microsoft Academic Search

The protective effect of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a selenoorganic compound, against hydrogen peroxide (H2O2)-induced cytotoxicity and DNA damage was investigated in a human hepatoma cell line, HepG2. The inhibitory effect of H2O2 on cell growth was determined using the tetrazolium dye colorimetric test (MTT test), and the cytotoxicity and lipid peroxidation were estimated by lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA)

Cheng-Feng Yang; Han-Ming Shen; Choon-Nam Ong

1999-01-01

204

Protective effect of hydroxytyrosol against acrylamide-induced cytotoxicity and DNA damage in HepG2 cells  

Microsoft Academic Search

The chemoprotective effect of hydroxytyrosol (HT) against acrylamide (AA)-induced cytotoxicity and DNA damage was investigated in a human hepatoma cell line, HepG2. The cytotoxicity was estimated by methyl thiazol tetrazolium bromide (MTT) assay. The comet assay was used to monitor DNA damage. The intracellular reactive oxygen species (ROS) formation and the level of oxidative DNA damage were estimated by using

Xiaomei Zhang; Jun Cao; Liping Jiang; Chenyan Geng; Laifu Zhong

2009-01-01

205

Lipid-coated Cisplatin nanoparticles induce neighboring effect and exhibit enhanced anticancer efficacy.  

PubMed

Encapsulation of cisplatin (CDDP) into nanoparticles (NPs) with high drug loading and encapsulation efficiency has been difficult due to the poor solubility of CDDP. However, this barrier has been overcome with a reverse microemulsion method appropriating CDDP's poor solubility to our advantage promoting the synthesis of a pure cisplatin nanoparticle with a high drug loading capacity (approximately 80.8 wt %). Actively targeted CDDP NPs exhibited significant accumulation in human A375M melanoma tumor cells in vivo. In addition, CDDP NPs achieved potent antitumor efficacy through the neighboring effect at a dose of 1 mg/kg when injected weekly via iv without inducing nephrotoxicity. The neighboring effect regards an observation made in vivo when the tumor cells that took up CDDP NPs released active drug following apoptosis. Via diffusion, surrounding cells that were previously unaffected showed intake of the released drug and their apoptosis soon followed. This observation was also made in vitro when A375M melanoma tumor cells incubated with CDDP NPs exhibited release of active drug and induced apoptosis on untreated neighboring cells. However, the neighboring effect was unique to rapidly proliferating tumor cells. Liver functional parameters and H&E staining of liver tissue in vivo failed to detect any difference between CDDP NP treated and control groups in terms of tissue health. By simultaneously promoting an increase in cytotoxicity and a lesser degree of side effects over free CDDP, CDDP NPs show great therapeutic potential with lower doses of drug while enhancing anticancer effectiveness. PMID:24083505

Guo, Shutao; Wang, Yuhua; Miao, Lei; Xu, Zhenghong; Lin, C Michael; Zhang, Yuan; Huang, Leaf

2013-11-26

206

In Caenorhabditis elegans Nanoparticle-Bio-Interactions Become Transparent: Silica-Nanoparticles Induce Reproductive Senescence  

PubMed Central

While expectations and applications of nanotechnologies grow exponentially, little is known about interactions of engineered nanoparticles with multicellular organisms. Here we propose the transparent roundworm Caenorhabditis elegans as a simple but anatomically and biologically well defined animal model that allows for whole organism analyses of nanoparticle-bio-interactions. Microscopic techniques showed that fluorescently labelled nanoparticles are efficiently taken up by the worms during feeding, and translocate to primary organs such as epithelial cells of the intestine, as well as secondary organs belonging to the reproductive tract. The life span of nanoparticle-fed Caenorhabditis elegans remained unchanged, whereas a reduction of progeny production was observed in silica-nanoparticle exposed worms versus untreated controls. This reduction was accompanied by a significant increase of the ‘bag of worms’ phenotype that is characterized by failed egg-laying and usually occurs in aged wild type worms. Experimental exclusion of developmental defects suggests that silica-nanoparticles induce an age-related degeneration of reproductive organs, and thus set a research platform for both, detailed elucidation of molecular mechanisms and high throughput screening of different nanomaterials by analyses of progeny production. PMID:19672302

Bossinger, Olaf; von Mikecz, Anna

2009-01-01

207

In vitro cytotoxicity of hydrothermally synthesized ZnO nanoparticles on human periodontal ligament fibroblast and mouse dermal fibroblast cells.  

PubMed

The use of metal oxide nanoparticles (NPs) in industrial applications has been expanding, as a consequence, risk of human exposure increases. In this study, the potential toxic effects of zinc oxide (ZnO) NPs on human periodontal ligament fibroblast cells (hPDLFs) and on mouse dermal fibroblast cells (mDFs) were evaluated in vitro. We synthesized ZnO NPs (particle size; 7-8 nm) by the hydrothermal method. Characterization assays were performed with atomic force microscopy, Braun-Emmet-Teller analysis, and dynamic light scattering. The hPDLFs and mDFs were incubated with the NPs with concentrations of 0.1, 1, 10, 50 and 100 ?g/mL for 6, 24 and 48h. Under the control and NP-exposed conditions, we have made different types of measurements for cell viability and morphology, membrane leakage and intracellular reactive oxygen species generation. Also, we monitored cell responses to ZnO NPs using an impedance measurement system in real-time. While the morphological changes were visualized using scanning electron microscopy, the subcellular localization of NPs was investigated by transmission electron microscopy. Results indicated that ZnO NPs have significant toxic effects on both of the primary fibroblastic cells at concentrations of ?50-100 ?g/mL. The cytotoxicity of ZnO NPs on fibroblasts depended on concentration and duration of exposure. PMID:25016134

Seker, Sükran; Elçin, A Eser; Yumak, Tu?rul; S?na?, Ali; Elçin, Y Murat

2014-12-01

208

Enhanced accumulation of curcumin and temozolomide loaded magnetic nanoparticles executes profound cytotoxic effect in glioblastoma spheroid model.  

PubMed

Glioblastomas (GBMs) are highly lethal primary brain tumours. Treatment of these malignant gliomas remains ineffective as these are extremely resistant to chemotherapeutic applications. Furthermore, combination therapy for cancer treatment is becoming more popular because it generates synergistic anticancer effects, by reducing individual drug-related toxicity and associated side effects. Currently, magnetic nanoparticles (MNPs) based drug delivery system has attracted much more attention owing to its intrinsic magnetic properties and drug loading capacity. In the present study, MNPs based drug delivery approach for co-delivering of potent chemotherapeutic drugs such as Curcumin (herbal drug) and Temozolomide (DNA methylating agent) has been implemented. The dual drug loaded MNPs formulations were evaluated in two-dimensional (2-D) monolayer culture and three-dimensional (3-D) tumour spheroid culture of T-98G cells for understanding the therapeutic discrepancy. The dual drug loaded MNPs formulations demonstrated higher cytotoxic effect than single drug loaded MNPs formulations as compared to their corresponding native drugs in 2-D and 3-D culture. The combination index (CI) analysis revealed synergistic mode of action of dual drug loaded MNPs formulations, which was further confirmed by cell death induction assay mediated by acridine orange (AO)/propidium iodide (PI) staining, illustrating higher efficacy of the formulation towards GBM therapy. PMID:23891772

Dilnawaz, Fahima; Sahoo, Sanjeeb Kumar

2013-11-01

209

Combined cytotoxic and anti-invasive properties of redox-active nanoparticles in tumor-stroma interactions.  

PubMed

Tumor-stroma interaction plays an important role in tumor progression. Myofibroblasts, pivotal for tumor progression, populate the microecosystem of reactive stroma. The formation of myofibroblasts is mediated by tumor derived transforming growth factor ?1 (TGF?1) which initiates a reactive oxygen species cell type dependent expression of alpha-smooth muscle actin, a biomarker for myofibroblastic cells. Myofibroblasts express and secrete proinvasive factors significantly increasing the invasive capacity of tumor cells via paracrine mechanisms. Although antioxidants prevent myofibroblast formation, the same antioxidants increase the aggressive behavior of the tumor cells. In this study, the question was addressed of whether redox-active polymer-coated cerium oxide nanoparticles (CNP, nanoceria) affect myofibroblast formation, cell toxicity, and tumor invasion. Herein, nanoceria downregulate both the expression of alpha-smooth muscle actin positive myofibroblastic cells and the invasion of tumor cells. Furthermore, concentrations of nanoceria being non-toxic for normal (stromal) cells show a cytotoxic effect on squamous tumor cells. The treatment with redox-active CNP may form the basis for protection of stromal cells from the dominating influence of tumor cells in tumor-stroma interaction, thus being a promising strategy for chemoprevention of tumor invasion. PMID:21269688

Alili, Lirija; Sack, Maren; Karakoti, Ajay S; Teuber, Sarah; Puschmann, Katharina; Hirst, Suzanne M; Reilly, Christopher M; Zanger, Klaus; Stahl, Wilhelm; Das, Soumen; Seal, Sudipta; Brenneisen, Peter

2011-04-01

210

Preparation of water-soluble hyperbranched polyester nanoparticles with sulfonic acid functional groups and their micelles behavior, anticoagulant effect and cytotoxicity.  

PubMed

Biocompatibility of nanoparticles has been attracting great interest in the development of nanoscience and nanotechnology. Herein, the aliphatic water-soluble hyperbranched polyester nanoparticles with sulfonic acid functional groups (HBPE-SO3 NPs) were synthesized and characterized. They are amphiphilic polymeric nanoparticles with hydrophobic hyperbranched polyester (HBPE) core and hydrophilic sulfonic acid terminal groups. Based on our observations, we believe there are two forms of HBPE-SO3 NPs in water under different conditions: unimolecular micelles and large multimolecular micelles. The biocompatibility and anticoagulant effect of the HBPE-SO3 NPs were investigated using coagulation tests, hemolysis assay, morphological changes of red blood cells (RBCs), complement and platelet activation detection, and cytotoxicity (MTT). The results confirmed that the sulfonic acid terminal groups can substantially enhance the anticoagulant property of HBPE, and the HBPE-SO3 NPs have the potential to be used in nanomedicine due to their good bioproperties. PMID:23718279

Han, Qiaorong; Chen, Xiaohan; Niu, Yanlian; Zhao, Bo; Wang, Bingxiang; Mao, Chun; Chen, Libin; Shen, Jian

2013-07-01

211

Cytotoxic Effect of Icaritin and Its Mechanisms in Inducing Apoptosis in Human Burkitt Lymphoma Cell Line  

PubMed Central

Icaritin (ICT), a hydrolytic product of icariin from Epimedium genus, exhibits antitumor activities in several human solid-tumor and myeloid leukemia cells with extensive influence on various cell signal molecules, such as MAPKs being involved in cell proliferation and Bcl-2 participating in cell apoptosis. However, the effect of icaritin on Burkitt Lymphoma has not been elucidated. In the present study, we first screened the potential effect of icaritin on Burkitt lymphoma Raji and P3HR-1 cell lines and found that icaritin showed cytotoxicity in both cell lines. We further found that icaritin could significantly inhibit Raji cells proliferation with S-phase arrest of cell cycle and induced cell apoptosis accompanied by activation of caspase-8 and caspase-9 and cleavage of PARP. We also observed that icaritin was able to decrease Bcl-2 levels, thus shifting the Bcl-2/Bax ratio, and it could obviously reduce c-Myc, a specific molecular target in Burkitt lymphoma. Our findings demonstrated that icaritin showed cytotoxicity, inhibited cell growth, caused S arrest, and induced apoptosis in Burkitt lymphoma cells and provided a rationale for the further evaluation of icaritin for Burkitt lymphoma therapy. PMID:24895574

Yao, Can; Liu, Su-Fang; Chen, Long; Xi, Ya-Ming; Zhang, Wen; Zhang, Guang-Sen

2014-01-01

212

Mechanisms of cisplatin (cis-diamminodichloroplatinum II)-induced cytotoxicity and genotoxicity in yeast.  

PubMed

The antitumor drug, cisplatin (cis- diamminodichloroplatinum II), dissolved in both water and phosphate-buffered saline, was studied for its genotoxic and cytotoxic effects in the yeast, Saccharomyces cerevisiae. The results showed that the drug was both recombinagenic and mutagenic in the wild-type diploid strain D7. It was observed that both cytotoxicity and genotoxicity were greatly reduced when cisplatin was dissolved in phosphate-buffered saline compared to the aqueous solution. Cell survival analyses showed that the diploid strain (D7 rad 3), deficient in excision of UV-induced pyrimidine dimers or similar adducts, was hypersensitive to cisplatin. Another diploid strain (rad 52/rad 52), blocked in the repair of DNA double-strand breaks and recombination was also hypersensitive to the drug. Mitotic gene conversion was not observed in the rad 52/rad 52 diploid after the drug treatments, while it was reduced in the excision -deficient strain. Reverse mutations occurred in the excision-deficient strain (D7 rad 3), even at low doses of cisplatin. These results are discussed in relation to the possible mechanisms of cisplatin-induced cell death and genotoxicity. PMID:6374440

Hannan, M A; Zimmer, S G; Hazle, J

1984-06-01

213

Cetuximab attenuates its cytotoxic and radiosensitizing potential by inducing fibronectin biosynthesis.  

PubMed

Inherent and acquired resistance to targeted therapeutics continues to emerge as a major clinical obstacle. For example, resistance to EGF receptor targeting occurs commonly, more so than was expected, on the basis of preclinical work. Given emerging evidence that cancer cell-substrate interactions are important determinants of therapeutic sensitivity, we examined the impact of cell-fibronectin interactions on the efficacy of the EGF receptor antibody cetuximab, which is used widely for lung cancer treatment. Our results revealed the potential for cell-fibronectin interactions to induce radioresistance of human non-small cell lung cancer cells. Cell adhesion to fibronectin enhanced tumor cell radioresistance and attenuated the cytotoxic and radiosensitizing effects of cetuximab. Both in vitro and in vivo, we found that cetuximab treatment led to a remarkable induction of fibronectin biosynthesis. Mechanistic analyses revealed the induction was mediated by a p38-MAPK-ATF2 signaling pathway and that RNAi-mediated inhibition of fibronectin could elevate the cytotoxic and radiosensitizing potential of cetuximab. Taken together, our findings show how cell adhesion blunts cetuximab, which, by inducing fibronectin, generates a self-attenuating mechanism of drug resistance. PMID:23950208

Eke, Iris; Storch, Katja; Krause, Mechthild; Cordes, Nils

2013-10-01

214

A simple thermal decomposition synthesis, magnetic properties, and cytotoxicity of La0.7Sr0.3MnO3 nanoparticles  

NASA Astrophysics Data System (ADS)

This study reports the new and simple synthesis of magnetic La0.7Sr0.3MnO3 (LSMO) nanoparticles by thermal decomposition method using acetate salts of La, Sr and Mn as starting materials. To obtain the LSMO nanoparticles, thermal decomposition of the precursor is carried out at the temperatures of 600, 700, 800, 900, and 1000°C for 6 hours. The synthesized LSMO nanoparticles were characterized by XRD, FT-IR, TEM and SEM. Structural characterization shows that the prepared particles consisted of two phases of LaMnO3 (LMO) and LSMO with crystallite sizes ranging from 18 to 55 nm. All the prepared samples have a perovskite structure which changes from cubic to rhombohedral with the increase in the thermal decomposition temperature. Basic magnetic characteristics such as saturation magnetization ( M S) and coercive field ( H C) are evaluated by sample vibrating magnetometry at room temperature (20°C). The samples show soft ferromagnetic behavior with M S values of ˜9-55 emu/g and H C values of ˜8-37 Oe, depending on the crystallite size and thermal decomposition temperature. The relationship between the crystallite size and the magnetic properties is presented and discussed. The cytotoxicity of synthesized LSMO nanoparticles was also evaluated with NIH 3T3 cells and the result showed that the synthesized nanoparticles were not toxic to the cells as determined from cell viability in response to the liquid extraction of LSMO nanoparticles.

Daengsakul, Sujittra; Mongkolkachit, Charusporn; Thomas, Chunpen; Siri, Sineenat; Thomas, Ian; Amornkitbamrung, Vittaya; Maensiri, Santi

2009-08-01

215

Nickel (II)-induced cytotoxicity and apoptosis in human proximal tubule cells through a ROS- and mitochondria-mediated pathway  

SciTech Connect

Nickel compounds are known to be toxic and carcinogenic in kidney and lung. In this present study, we investigated the roles of reactive oxygen species (ROS) and mitochondria in nickel (II) acetate-induced cytotoxicity and apoptosis in the HK-2 human renal cell line. The results showed that the cytotoxic effects of nickel (II) involved significant cell death and DNA damage. Nickel (II) increased the generation of ROS and induced a noticeable reduction of mitochondrial membrane potential (MMP). Analysis of the sub-G1 phase showed a significant increase in apoptosis in HK-2 cells after nickel (II) treatment. Pretreatment with N-acetylcysteine (NAC) not only inhibited nickel (II)-induced cell death and DNA damage, but also significantly prevented nickel (II)-induced loss of MMP and apoptosis. Cell apoptosis triggered by nickel (II) was characterized by the reduced protein expression of Bcl-2 and Bcl-xL and the induced the protein expression of Bad, Bcl-Xs, Bax, cytochrome c and caspases 9, 3 and 6. The regulation of the expression of Bcl-2-family proteins, the release of cytochrome c and the activation of caspases 9, 3 and 6 were inhibited in the presence of NAC. These results suggest that nickel (II) induces cytotoxicity and apoptosis in HK-2 cells via ROS generation and that the mitochondria-mediated apoptotic signaling pathway may be involved in the positive regulation of nickel (II)-induced renal cytotoxicity.

Wang, Yi-Fen; Shyu, Huey-Wen [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chang, Yi-Chuang [Department of Nursing, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Nursing, Fooyin University, Kaohsiung, Taiwan (China); Tseng, Wei-Chang [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Huang, Yeou-Lih [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Lin, Kuan-Hua; Chou, Miao-Chen; Liu, Heng-Ling [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chen, Chang-Yu, E-mail: mt037@mail.fy.edu.tw [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)] [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)

2012-03-01

216

Magnetic and Cytotoxicity Properties of La1- x Sr x MnO3 (0 ? x ? 0.5) Nanoparticles Prepared by a Simple Thermal Hydro-Decomposition  

NASA Astrophysics Data System (ADS)

This study reports the magnetic and cytotoxicity properties of magnetic nanoparticles of La1- x Sr x MnO3 (LSMO) with x = 0, 0.1, 0.2, 0.3, 0.4, and 0.5 by a simple thermal decomposition method by using acetate salts of La, Sr, and Mn as starting materials in aqueous solution. To obtain the LSMO nanoparticles, thermal decomposition of the precursor was carried out at the temperatures of 600, 700, 800, and 900 °C for 6 h. The synthesized LSMO nanoparticles were characterized by XRD, FT-IR, TEM, and SEM. Structural characterization shows that the prepared particles consist of two phases of LaMnO3 (LMO) and LSMO with crystallite sizes ranging from 20 nm to 87 nm. All the prepared samples have a perovskite structure with transformation from cubic to rhombohedral at thermal decomposition temperature higher than 900 °C in LSMO samples of x ? 0.3. Basic magnetic characteristics such as saturated magnetization ( M S) and coercive field ( H C) were evaluated by vibrating sample magnetometry at room temperature (20 °C). The samples show paramagnetic behavior for all the samples with x = 0 or LMO, and a superparamagnetic behavior for the other samples having M S values of ~20-47 emu/g and the H C values of ~10-40 Oe, depending on the crystallite size and thermal decomposition temperature. Cytotoxicity of the synthesized LSMO nanoparticles was also evaluated with NIH 3T3 cells and the result shows that the synthesized nanoparticles were not toxic to the cells as determined from cell viability in response to the liquid extract of LSMO nanoparticles.

Daengsakul, Sujittra; Thomas, Chunpen; Thomas, Ian; Mongkolkachit, Charusporn; Siri, Sineenat; Amornkitbamrung, Vittaya; Maensiri, Santi

2009-08-01

217

Synthesis, Characterization, In Vitro Cytotoxicity, and Apoptosis-Inducing Properties of Ruthenium(II) Complexes  

PubMed Central

Two new Ru(II) complexes, [Ru(bpy)2(FAMP)](ClO4)2 1 and 2, are synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H nuclear magnetic resonance. The in vitro cytotoxicities and apoptosis-inducing properties of these complexes are extensively studied. Complexes 1 and 2 exhibit potent antiproliferative activities against a panel of human cancer cell lines. The cell cycle analysis shows that complexes 1 and 2 exhibit effective cell growth inhibition by triggering G0/G1 phase arrest and inducing apoptosis by mitochondrial dysfunction. The in vitro DNA binding properties of the two complexes are investigated by different spectrophotometric methods and viscosity measurements. PMID:24804832

Xu, Li; Zhong, Nan-Jing; Xie, Yang-Yin; Huang, Hong-Liang; Jiang, Guang-Bin; Liu, Yun-Jun

2014-01-01

218

Di-tert-butylhydroxylated flavonoids protect endothelial cells against oxidized LDL-induced cytotoxicity.  

PubMed

The protective effect of di-tert-butylhydroxylated flavonoids (chalcones and arylidenes) against minimally oxidized LDL (mO-LDL)-induced cytotoxicity was studied in cultured bovine aortic endothelial cells. Most of the tested compounds decreased aldehydes formation in medium containing mO-LDL, but their capacity to inhibit LDL oxidation in the cellular medium was not sufficient to totally reduce the cellular toxicity of mO-LDL. Most of the tested flavonoids improved the integrity of cells exposed to mO-LDL, whereas butylated hydroxytoluene was ineffective and quercetin worsened the toxicity of mO-LDL. Moreover these flavonoids induced an increase in GSH cellular levels and their protective effects might be because of their inability to reduce metal ion. Arylidene 6 substituted at position 7 by a hydroxyl group was the most potent compound. PMID:11835624

Furman, C; Lebeau, J; Fruchart, J; Bernier, J; Duriez, P; Cotelle, N; Teissier, E

2001-01-01

219

Platinum nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations.  

PubMed

Three differently sized, highly dispersed platinum nanoparticle (Pt-NP) preparations were generated by supercritical fluid reactive deposition (SFRD) and deposited on a ?-cyclodextrin matrix. The average particle size and size distribution were steered by the precursor reduction conditions, resulting in particle preparations of <20, <100 and >100 nm as characterised by TEM and SEM. As reported previously, these Pt-NPs were found to cause DNA strand breaks in human colon carcinoma cells (HT29) in a concentration- and time-dependent manner and a distinct size dependency. Here, we addressed the question whether Pt-NPs might affect directly DNA integrity in these cells and thus behave analogous to platinum-based chemotherapeutics such as cisplatin. Therefore, DNA-associated Pt as well as the translocation of Pt-NPs through a Caco-2 monolayer was quantified by ICP-MS. STEM imaging demonstrated that Pt-NPs were taken up into HT29 cells in their particulate and aggregated form, but appear not to translocate into the nucleus or interact with mitochondria. The platinum content of the DNA of HT29 cells was found to increase in a time- and concentration-dependent manner with a maximal effect at 1,000 ng/cm(2). ICP-MS analysis of the cell culture medium indicated the formation of soluble Pt species, although to a limited extent. The observations suggest that DNA strand breaks mediated by metallic Pt-NPs are caused by Pt ions forming during the incubation of cells with these nanoparticles. PMID:21229235

Gehrke, Helge; Pelka, Joanna; Hartinger, Christian G; Blank, Holger; Bleimund, Felix; Schneider, Reinhard; Gerthsen, Dagmar; Bräse, Stefan; Crone, Marlene; Türk, Michael; Marko, Doris

2011-07-01

220

Nanoparticle-induced twist-grain boundary phase  

NASA Astrophysics Data System (ADS)

By means of high-resolution ac calorimetry and polarizing optical microscopy, it is demonstrated that surface-functionalized spherical CdSSe nanoparticles induce a twist-grain boundary phase when dispersed in a chiral liquid crystal. These nanoparticles can effectively stabilize the one-dimensional lattice of screw dislocations, thus establishing the twist-grain boundary order between the cholesteric and the smectic-A phases. A Landau-de Gennes-Ginzburg model is used to analyze the impact of nanoparticles on widening the temperature range of molecular organizations possessing a lattice of screw dislocations. We show that in addition to the defect-core-replacement mechanism, the saddle-splay elasticity may also play a significant role.

Tr?ek, Maja; Cordoyiannis, George; Tzitzios, Vassilios; Kralj, Samo; Nounesis, George; Lelidis, Ioannis; Kutnjak, Zdravko

2014-09-01

221

Catalase ameliorates polychlorinated biphenyl-induced cytotoxicity in non-malignant human breast epithelial cells  

PubMed Central

Polychlorinated biphenyls (PCBs) are environmental chemical contaminants believed to adversely affect cellular processes. We investigated the hypothesis that PCB-induced changes in the levels of cellular reactive oxygen species (ROS) induce DNA damage resulting in cytotoxicity. Exponentially growing cultures of human non-malignant breast epithelial cells (MCF10A) were incubated with PCBs for 3 days and assayed for cell number, ROS levels, DNA damage, and cytotoxicity. Exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) or 2-(4-chlorophenyl)benzo-1,4-quinone (4-Cl-BQ), a metabolite of 4-chlorobiphenyl (PCB3) significantly decreased cell number, MTS reduction, and increased the percentage of cells with sub G1 DNA content. Results from electron paramagnetic resonance (EPR) spectroscopy showed a 4-fold increase in the steady-state levels of ROS, which was suppressed in cells pre-treated with catalase. EPR measurements in cells treated with 4-Cl-BQ detected the presence of a semiquinone radical, suggesting that the increased levels of ROS could be due to the redox-cycling of 4-Cl-BQ. A dose-dependent increase in micronuclei frequency was observed in PCB-treated cells, consistent with an increase in histone 2AX-phosphorylation. Treatment of cells with catalase blunted the PCB-induced increase in micronuclei frequency and H2AX phosphorylation that was consistent with an increase in cell survival. Our results demonstrate a PCB-induced increase in cellular levels of ROS causing DNA damage, resulting in cell killing. PMID:18691649

Venkatesha, Venkatasubbaiah A.; Venkataraman, Sujatha; Sarsour, Ehab H.; Kalen, Amanda L.; Buettner, Garry R.; Robertson, Larry W.; Lehmler, Hans-Joachim; Goswami, Prabhat C.

2008-01-01

222

Aqueous extract of unfermented honeybush (Cyclopia maculata) attenuates STZ-induced diabetes and ?-cell cytotoxicity.  

PubMed

New strategies, which include ?-cell protection, are required in the treatment of T2D, as current drugs demonstrate little or no capacity to directly protect the vulnerable ?-cell against diabetes-induced cytotoxicity. In this study we investigated the ameliorative effect of pre-treatment with an aqueous extract of unfermented Cyclopia maculata (honeybush) on STZ-induced diabetes and pancreatic ?-cell cytotoxicity in Wistar rats after demonstrating a protective effect in vitro in RIN-5F cells. The amelioration of STZ-induced diabetes was seen in the reduction of the area under the curve, determined by the oral glucose tolerance test, as well as fasting glucose levels in extract-treated rats. Pre-treatment with extract also improved serum triglyceride levels and the glucose-to-insulin ratio. Pre-treatment with the extract or the drug, metformin, increased the ?-cell area in islets, with a concomitant increase in ?-cell proliferation at the higher extract dose (300 mg/kg/d), but not the lower dose (30 mg/kg/d). Subsequently, the in vitro tritiated thymidine incorporation assay showed that the extract was not mitogenic in RIN-5F cells. STZ-induced elevation of plasma nitrite levels was reduced in extract-treated rats, but no changes were observed in their serum catalase, serum glutathione, liver lipid peroxidation and liver nitrotyrosine levels. Pre-treating the rats with extract ameliorated the diabetic effect of STZ in Wistar rats, with evidence of pancreatic ?-cells protection, attributed to the presence of high levels of antioxidants such as the xanthones, mangiferin and isomangiferin. PMID:24853761

Chellan, Nireshni; Joubert, Elizabeth; Strijdom, Hans; Roux, Candice; Louw, Johan; Muller, Christo J F

2014-06-01

223

Streptozotocin-Induced Cytotoxicity, Oxidative Stress and Mitochondrial Dysfunction in Human Hepatoma HepG2 Cells  

PubMed Central

Streptozotocin (STZ) is an antibiotic often used in the treatment of different types of cancers. It is also highly cytotoxic to the pancreatic beta-cells and therefore is commonly used to induce experimental type 1 diabetes in rodents. Resistance towards STZ-induced cytotoxicity in cancer cells has also been reported. Our previous studies have reported organ-specific toxicity and metabolic alterations in STZ-induced diabetic rats. STZ induces oxidative stress and metabolic complications. The precise molecular mechanism of STZ-induced toxicity in different tissues and carcinomas is, however, unclear. We have, therefore, investigated the mechanism of cytotoxicity of STZ in HepG2 hepatoma cells in culture. Cells were treated with different doses of STZ for various time intervals and the cytotoxicity was studied by observing the alterations in oxidative stress, mitochondrial redox and metabolic functions. STZ induced ROS and RNS formation and oxidative stress as measured by an increase in the lipid peroxidation as well as alterations in the GSH-dependent antioxidant metabolism. The mitochondria appear to be a highly sensitive target for STZ toxicity. The mitochondrial membrane potential and enzyme activities were altered in STZ treated cells resulting in the inhibition of ATP synthesis. ROS-sensitive mitochondrial aconitase activity was markedly inhibited suggesting increased oxidative stress in STZ-induced mitochondrial toxicity. These results suggest that STZ-induced cytotoxicity in HepG2 cells is mediated, at least in part, by the increase in ROS/RNS production, oxidative stress and mitochondrial dysfunction. Our study may be significant for better understanding the mechanisms of STZ action in chemotherapy and drug induced toxicity. PMID:22754329

Raza, Haider; John, Annie

2012-01-01

224

Peptide-induced patterning of gold nanoparticle thin films  

NASA Astrophysics Data System (ADS)

In this work, the use of patterned proteins and peptides for the deposition of gold nanoparticles on several substrates with different surface chemistries is presented. The patterned biomolecule on the surface acts as a catalyst to precipitate gold nanoparticles from a precursor solution of HAuCl 4 onto the substrate. The peptide patterning on the surfaces was accomplished by physical adsorption or covalent attachment. It was shown that by using covalent attachment with a linker molecule, the influence of the surface properties from the different substrates on the biomolecule adsorption and subsequent nanoparticle deposition could be avoided. By adjusting the reaction conditions such as pH or HAuCl 4 concentration, the sizes and morphologies of deposited gold nanoparticle agglomerates could be controlled. Two biomolecules were used for this experiment, 3XFLAG peptide and bovine serum albumin (BSA). A micro-transfer molding technique was used to pattern the peptides on the substrates, in which a pre-patterned poly(dimethylsiloxane) (PDMS) mold was used to deposit a lift-off pattern of polypropylmethacrylate (PPMA) on the various substrates. The proteins were either physically adsorbed or covalently attached to the substrates, and an aqueous HAuCl 4 solution was applied on the substrates with the protein micropatterns, causing the precipitation of gold nanoparticles onto the patterns. SEM, AFM, and Electron Beam Induced Current (EBIC) were used for characterization.

Borteh, Hassan M.; Ferrell, Nicholas J.; Butler, Randall T.; Olesik, Susan V.; Hansford, Derek J.

2011-10-01

225

Cytotoxicity and immunological responses following oral vaccination of nanoencapsulated avian influenza virus H5 DNA vaccine with green synthesis silver nanoparticles.  

PubMed

DNA formulations provide the basis for safe and cost effective vaccine. Low efficiency is often observed in the delivery of DNA vaccines. In order to assess a new strategy for oral DNA vaccine formulation and delivery, plasmid encoding hemagglutinin (HA) gene of avian influenza virus, A/Ck/Malaysia/5858/04 (H5N1) (pcDNA3.1/H5) was formulated using green synthesis of sliver nanoparticles (AgNP) with polyethylene glycol (PEG). AgNP were successfully synthesized uniformly dispersed with size in the range of 4 to 18 nm with an average size of 11 nm. Cytotoxicity of the prepared AgNP was investigated in vitro and in vivo using MCF-7 cells and cytokine expression, respectively. At the concentration of -5 log??AgNP, no cytotoxic effects were detected in MCF-7 cells with 9.5% cell death compared to the control. One-day-old specific pathogen-free (SPF) chicks immunized once by oral gavage with 10 ?l of pcDNA3.1/H5 (200 ng/ml) nanoencapsulated with 40 ?l AgNP (3.7×10?² ?g of Ag) showed no clinical manifestations. PCR successfully detect the AgNP/H5 plasmid from the duodenum of the inoculated chicken as early as 1h post-immunization. Immunization of chickens with AgNP/H5 enhanced both pro inflammatory and Th1-like expressions, although no significant differences were recorded in the chickens inoculated with AgNP, AgNP/pcDNA3.1 and the control. In addition, serum samples collected from immunized chickens with AgNP/H5 showed rapidly increasing antibody against H5 on day 14 after immunization. The highest average antibody titres were detected on day 35 post-immunization at 51.2±7.5. AgNP/H5 also elicited both CD4+ and CD8+ T cells in the immunized chickens as early as day 14 after immunization, at 7.5±2.0 and 20±1.9 percentage, respectively. Hence, single oral administrations of AgNP/H5 led to induce both the antibody and cell-mediated immune responses as well as enhanced cytokine production. PMID:22549012

Jazayeri, Seyed Davoud; Ideris, Aini; Zakaria, Zunita; Shameli, Kamyar; Moeini, Hassan; Omar, Abdul Rahman

2012-07-10

226

NMO sera down-regulate AQP4 in human astrocyte and induce cytotoxicity independent of complement.  

PubMed

Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are highly specific for neuromyelitis optica (NMO). However, the molecular mechanism of NMO still remains unclear. The purpose of this study was to identify the possible humoral mechanisms responsible for the occurrence of astrocytic damage. Human primary astrocytes (AST) were immortalized by retroviral vectors harboring temperature-sensitive SV40 T antigen gene and AQP4 cDNA (M23), designated as hAST-AQP4. The effects of NMO sera on the content and localization of AQP4, including cytotoxicity and astrocytic morphology, were evaluated. In addition, this study examined whether the amount and localization of AQP4 protein in astrocytes were influenced by direct contact with the immortalized human brain microvascular endothelial cell line, TY09. NMO sera alone induced cytotoxicity and addition of complement had a more harmful effect on hAST-AQP4. NMO sera also decreased AQP4 mRNA and protein. NMO sera alone up-regulated TNF? and IL-6 in astrocytes and co-incubation with anti-TNF? and anti-IL-6 neutralizing antibodies blocked both the cytotoxicity and reduction of AQP4 in astrocytes. In the experiment using the in vitro BBB models, AQP4 protein mainly localized at the astrocytic membrane after co-culture with TY09, in contact with TY09. The future elucidation of factors that up-regulate AQP4 in astrocytes presumably released by blood brain barrier forming endothelial cells and that block the production of inflammatory cytokines may therefore lead to the development of a novel therapeutic strategy. PMID:23809190

Haruki, Hiroyo; Sano, Yasuteru; Shimizu, Fumitaka; Omoto, Masatoshi; Tasaki, Ayako; Oishi, Mariko; Koga, Michiaki; Saito, Kazuyuki; Takahashi, Toshiyuki; Nakada, Tsutomu; Kanda, Takashi

2013-08-15

227

Cytotoxicity effects of metal oxide nanoparticles in human tumor cell lines  

NASA Astrophysics Data System (ADS)

Metallic and metal oxide nanoparticles (Nps) have a wide range of applications in various settings including household, cosmetics and chemical industries, as well as for coatings. Nevertheless, an in-depth study of the potential toxic effects of these Nps is still needed, in order to fulfill the mandatory requirement of ensuring the safety of workers, patients and the general public. In this study, Quick Cell colorimetric assays were used to evaluate the in vitro toxicity of different metal oxide Nps [Fe(II,III)Ox, TiOx, ZnO and CeO2] in several cell lines. The ZnO Nps were found to be highly toxic, with a lethal dose <=100 ?g/ml for all the cell lines studied. Western blot was also used to test the ability of the different Nps to activate the complement pathway. However, no activation of this cascade was observed when the Nps were added. In addition, the aggregation state and charge of the Nps in culture media was studied by dynamic light scattering (DLS) and measurement of zeta potential. Transmission Electron Microscopy was used to analyze Np uptake and localization at the cellular level.

Lozano, T.; Rey, M.; Rojas, E.; Moya, S.; Fleddermann, J.; Estrela-Lopis, I.; Donath, E.; Wang, B.; Mao, Z.; Gao, C.; González-Fernández, África

2011-07-01

228

The cytotoxic effects of titanium oxide and zinc oxide nanoparticles oh Human Cervical Adenocarcinoma cell membranes  

NASA Astrophysics Data System (ADS)

The importance of titanium dioxide (TiO2) and zinc oxide (ZnO), inorganic metal oxides nanoparticles (NPs) stems from their ubiquitous applications in personal care products, solar cells and food whitening agents. Hence, these NPs come in direct contact with the skin, digestive tracts and are absorbed into human tissues. Currently, TiO2 and ZnO are considered safe commercial ingredients by the material safety data sheets with no reported evidence of carcinogenicity or ecotoxicity, and do not classify either NP as a toxic substance. This study examined the direct effects of TiO2 and ZnO on HeLa cells, a human cervical adenocarcinonma cell line, and their membrane mechanics. The whole cell patch-clamp technique was used in addition to immunohistochemistry staining, TEM and atomic force microscopy (AFM). Additionally, we examined the effects of dexamethasone (DXM), a glucocorticoid steroid known to have an effect on cell membrane mechanics. Overall, TiO2 and ZnO seemed to have an adverse effect on cell membrane mechanics by effecting cell proliferation, altering cellular structure, decreasing cell-cell adhesion, activating existing ion channels, increasing membrane permeability, and possibly disrupting cell signaling.

Mironava, Tatsiana; Applebaum, Ariella; Applebaum, Eliana; Guterman, Shoshana; Applebaum, Kayla; Grossman, Daniel; Gordon, Chris; Brink, Peter; Wang, H. Z.; Rafailovich, Miriam

2013-03-01

229

Lentinula edodes (Shiitake) mushroom extract protects against hydrogen peroxide induced cytotoxicity in peripheral blood mononuclear cells.  

PubMed

Lentinula edodes (Berk) Pegler, commonly known as Shiitake mushroom has been used as medicinal food in Asian countries, especially in China and Japan and is believed to possess strong immunomodulatory property. In the present study, the methanolic extract of the fruit bodies of L. edodes was investigated for cytoprotective effect against H2O2-induced cytotoxicity in human peripheral blood mononuclear cells (PBMCs) by measuring the activities of xanthine oxidase (XO) and glutathione peroxidase (GPx) . H2O2 at a concentration of 5 microM caused 50% inhibition of PBMCs viability. The extract improved the PBMC viability and exerted a dose-dependent protection against H2O2-induced cytotoxicity. At 100 microg/ml of extract concentration, the cell viability increased by 60% compared with the PBMCs incubated with H2O2 alone. The extract also inhibited XO activity in PBMC, while showing moderate stimulatory effect on GPx. However, in the presence of H2O2 alone, both the enzyme activities were increased significantly. The GPx activity increased, possibly in response to the increased availability of H2O2 in the cell. When the cells were pretreated with the extract and washed (to remove the extract) prior to the addition of H2O2, the GPx and XO activities as well as the cell viability were comparable to those when incubated with the extract alone. Thus, it is suggested that one of the possible mechanisms via which L. edodes methanolic extract confers protection against H2O2-induced oxidative stress in PBMC is by inhibiting the superoxide-producing XO and increasing GPx activity which could rapidly inactivate H2O2. PMID:19517993

Kuppusamy, U R; Chong, Y L; Mahmood, A A; Indran, M; Abdullah, Noorlidah; Vikineswary, S

2009-04-01

230

Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells  

Microsoft Academic Search

Cerium oxide nanoparticles of different sizes (15, 25, 30, 45nm) were prepared by the supercritical synthesis method, and cytotoxicity was evaluated using cultured human lung epithelial cells (BEAS-2B). Exposure of the cultured cells to nanoparticles (5, 10, 20, 40?g\\/ml) led to cell death, ROS increase, GSH decrease, and the inductions of oxidative stress-related genes such as heme oxygenase-1, catalase, glutathione

Eun-Jung Park; Jinhee Choi; Young-Kwon Park

2008-01-01

231

Protective effects of Eucommia ulmoides Oliv. bark and leaf on amyloid ?-induced cytotoxicity.  

PubMed

The objectives of this study were to investigate the protective effects of Eucommia ulmoides Oliv. (EUO) bark and leaf against cytotoxicity induced by amyloid-? peptide (A?) and to explore their active components. The PC-12 cells injury mediated by A?(25-35) was employed to assess the neuroprotective effects of EUO bark, EUO leaf and various compounds. Intracellular Ca(2+) determination, MTT reduction assay, lactate dehydrogenase leakage evaluation and HO33258/PI staining were used to quantitatively or qualitatively evaluate cell viability and injury. The organic solvents partition and the macroporous resin separation were also applied to tracing the active constituents of EUO bark. Moreover, the effects of 8 compounds (3 iridoid glucoside, 3 phenylpripanoids and 2 flavonoids) were tested to identify the active compounds of EUO leaf. The results demonstrated that the water extracts of EUO barks and leaves, geniposidic acid and chlorogenic acid could efficiently protect PC-12 cells against the cytotoxicity of A?(25-35). This research suggests that EUO may represent a potential treatment strategy for Alzheimer's disease. Meanwhile, geniposidic acid and chlorogenic acid are the major active constituents of EUO barks and leaves, respectively. PMID:21784025

Zhou, Yongqiang; Liang, Min; Li, Weize; Li, Kai; Li, Ping; Hu, Yuzhu; Yang, Zhonglin

2009-11-01

232

UVA-induced oxidative damage and cytotoxicity depend on the mode of exposure.  

PubMed

The reciprocity rule (Bunsen-Roscoe law) states that a photochemical reaction is directly proportional to the total energy dose, irrespective of the dose distribution. In photomedicine the validity of this law is usually taken for granted, although the influence of radiation intensity and dose distribution are largely unknown. We have examined in a tissue culture model the effects of fractionated versus single dose exposure to UV from a metal halide source on survival, DNA synthesis, glutathione, and oxidative membrane damage. Exposure to fractionated UVA was followed by an increased rate of cell death compared to single dose exposure, when intervals between fractions where short (10-120 min). Longer intervals had the opposite effect. Corresponding results were obtained for DNA synthesis (BrdU incorporation). The increased cytotoxicity of dose fractionation with short intervals could not be abrogated by non-enzymatic antioxidants (astaxanthin, ascorbic acid, alpha-tocopherol). Fractionated irradiation with short intervals led to higher degree of depletion of glutathione (GSH) and to enhanced formation of thiobarbituric acid reactive substances (TBARS) in comparison to an identical single dose. Long intervals between fractions induced opposite effects. Taken together, these data indicate that immediately after UVA exposure cells are more sensitive to a further oxidative attack making repeated exposure with short intervals more cytotoxic than continuous single dose UVA. This might have implications also for responses to UVA in vivo and further studies will have to extend these findings to the situation in healthy and diseased human skin. PMID:15896646

Merwald, Helga; Klosner, Gabriele; Kokesch, Claudia; Der-Petrossian, Manon; Hönigsmann, Herbert; Trautinger, Franz

2005-06-01

233

Methyllycaconitine Alleviates Amyloid-? Peptides-Induced Cytotoxicity in SH-SY5Y Cells  

PubMed Central

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. As the most common form of dementia, it affects more than 35 million people worldwide and is increasing. Excessive extracellular deposition of amyloid-? peptide (A?) is a pathologic feature of AD. Accumulating evidence indicates that macroautophagy is involved in the pathogenesis of AD, but its exact role is still unclear. Although major findings on the molecular mechanisms have been reported, there are still no effective treatments to prevent, halt, or reverse Alzheimer's disease. In this study, we investigated whether A?25–35 could trigger an autophagy process and inhibit the growth of SH-SY5Y cells. Furthermore, we examined the effect of methyllycaconitine (MLA) on the cytotoxity of A?25–35. MLA had a protective effect against cytotoxity of A?, which may be related to its inhibition of A?-induced autophagy and the involvement of the mammalian target of rapamycin pathway. Moreover, MLA had a good safety profile. MLA treatment may be a promising therapeutic tool for AD. PMID:25360664

Zheng, XiaoLei; Xie, ZhaoHong; Zhu, ZhengYu; Liu, Zhen; Wang, Yun; Wei, LiFei; Yang, Hui; Yang, HongNa; Liu, YiQing; Bi, JianZhong

2014-01-01

234

Fluorescence behavior of non-functionalized carbon nanoparticles and their in vitro applications in imaging and cytotoxic analysis of cancer cells.  

PubMed

We report fluorescence behavior in non-functionalized carbon nanoparticles (NCNP) prepared from lamp soot and their application in imaging of normal and cancer cells. Structural characterization of these particles by Raman spectroscopy showed characteristic peaks located at 1350 and 1590 cm(-1) corresponding to the diamond-like (D) and graphite-like (G) bands of the carbon allotropes respectively with the characteristic ratio I(D)/I(G)=2.24. X-ray diffraction study confirmed the presence of amorphous as well as graphitized carbon in these nanostructures with minimum grain size ?2 nm. A typical luminescence lifetime measured by time resolved fluorescence spectroscopy was obtained 3.54 ns. The photoluminescence behavior of these particles was excitation dependent and gave off blue, green and red fluorescence under UV, blue and green excitation, respectively. Cellular uptake of these NCNP yielded excellent results for cell imaging of human embryonic kidney, lung carcinoma and breast adenocarcinoma cells. Cell imaging was further correlated with cytotoxicity in the above mentioned cell lines and also in leukemia cell lines. Dose dependant cytotoxicity was observed after 24 h up to 48 h of incubation of nanoparticles. Fluorescence microscopy of nanoparticle-cell interaction clearly indicated aggregation of the particles. PMID:22088754

Kumar, Pradip; Meena, Ramavtar; Paulraj, R; Chanchal, A; Verma, A K; Bohidar, H B

2012-03-01

235

Transactivation of bad by vorinostat-induced acetylated p53 enhances doxorubicin-induced cytotoxicity in cervical cancer cells.  

PubMed

Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments. PMID:24525822

Lee, Sook-Jeong; Hwang, Sung-Ook; Noh, Eun Joo; Kim, Dong-Uk; Nam, Miyoung; Kim, Jong Hyeok; Nam, Joo Hyun; Hoe, Kwang-Lae

2014-01-01

236

Non-specific interaction of carbon nanotubes with the resazurin assay reagent: Impact on in vitro assessment of nanoparticle cytotoxicity.  

PubMed

In vitro cytotoxicity assays are essential tools in the screening of engineered nanomaterials (NM) for cellular toxicity. The resazurin live cell assay is widely used because it is non-destructive and is well suited for high-throughput platforms. However, NMs, in particular carbon nanotubes (CNT) can interfere in assays through quenching of transmitted light or fluorescence. We show that using the resazurin assay with time-point reading of clarified supernatants resolves this problem. Human lung epithelial (A549) and murine macrophage (J774A.1) cell lines were exposed to NMs in 96-well plates in 200?L of media/well. After 24h incubation, 100?L of supernatant was removed, replaced with resazurin reagent in culture media and aliquots at 10min and 120min were transferred to black-wall 96-well plates. The plates were quick-spun to sediment the residual CNTs and fluorescence was top-read (?Ex=540nm, ?Em=600nm). The procedure was validated for CNTs as well as silica nanoparticles (SiNP). There was no indication of reduction of resazurin by the CNTs. Stability of resorufin, the fluorescent product of the resazurin reduction was then assessed. We found that polar CNTs could decrease the fluorescence signal for resorufin, possibly through oxidation to resazurin or hyper-reduction to hydroxyresorufin. This effect can be easily quantified for elimination of the bias. We recommend that careful consideration must be given to fluorimetric/colorimetric in vitro toxicological assessments of optically/chemically active NMs in order to relieve any potential artifacts due to the NMs themselves. PMID:25283091

Breznan, Dalibor; Das, Dharani; MacKinnon-Roy, Christine; Simard, Benoit; Kumarathasan, Premkumari; Vincent, Renaud

2015-02-01

237

Self-reporter shikonin-Act-loaded solid lipid nanoparticle: formulation, physicochemical characterization and geno/cytotoxicity evaluation.  

PubMed

Shikonin and some of its derivative have approved apoptotic potential in different human cancer cell lines, and moreover have a dominant fluorescent emission at ?600nm. Here, to enhance shikonin-Act anti-proliferation properties, it was successfully incorporated in Solid Lipid Nanoparticles (SLNs) by the hot homogenization and entrapment efficiency (EE) of drug in SLNs was determined by ultrafiltration method. Scanning electron microscopy (SEM), laser diffractometry and zeta-sizer indicated that shikonin-Act-SLN were spherical and regular particles in the range of 70-120nm with polydispersity index (PI) of less than 0.10. The physical stability of shikonin-Act-loaded SLN in aqueous dispersion was evaluated in terms of size, PI, EE and drug leakage and the results showed that SLNs were stable upon storing three month. Long term in vitro release of the shikonin-Act was also approved. Cellular uptake of the shikonin-Act-SLN was examined by the in vitro fluorescent microscopy and facs flow cytometry analyses. In vivo rat imaging approved the penetrating capability of shikonin-Act-SLN emission through living tissues. In vitro anti-proliferation and genotoxicity evaluation by MTT and comet assay confirmed that shikonin-Act-SLN showed higher cytotoxic/antitumor potential than intact shikonin in terms of IC50 and DNA damage. This work provide sufficient information about improving of the therapeutic efficacy of the shikonin-Act, and also using of the shikonin-Act-SLN in bio-distribution studies during drug delivery investigation by incorporating in lipidic and colloidal drug delivery particles such as SLNs. PMID:24768857

Eskandani, Morteza; Nazemiyeh, Hossein

2014-08-01

238

Reduction of hexachlorocyclohexane-induced oxidative stress and cytotoxicity in rat liver by Emblica officinalis gaertn.  

PubMed

The effect of prefeeding of dehydrated E. officinalis (amla) powder at 5 and 10% levels on hexachlorocyclohexane (HCH)-induced changes in multicomponent antioxidant system and lipid peroxides in rat liver was studied. HCH induced significant elevation in hepatic malondialdehyde, conjugated dienes and hydroperoxides. The prefeeding of amla at 10% level could decrease the formation of these lipid peroxides significantly. The HCH abuse resulted in a significant reduction in hepatic glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G-6-PDH) and superoxide dismutase (SOD) activities with an elevation in the activities of glutathione peroxidase and gamma-glutamyl transpeptidase (GGT). On the other hand, the HCH-induced impairment in hepatic catalase, G-6-PDH and SOD activities were modulated by amla at the 10% level of intake. Prefeeding of amla at 5 and 10% levels appeared to reduce the HCH-induced raise in renal GGT activity. The results show the elevation of hepatic antioxidant system and reduction of cytotoxic products as a result of prefeeding of amla, which were otherwise affected by the HCH administration. PMID:17569287

Anilakumar, K R; Nagaraj, N S; Santhanam, K

2007-05-01

239

SN38 polymeric nanoparticles: in vitro cytotoxicity and in vivo antitumor efficacy in xenograft balb/c model with breast cancer versus irinotecan.  

PubMed

SN38 (7-ethyl-10-hydroxyl camptothecin), a potent metabolite of irinotecan, has been considered as an anticancer candidate. Its clinical development has been hampered due to its poor solubility. As a result, SN38 loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) was developed in current study to solve its poor water solubility problem while maintaining its cytotoxicity against cancer cells. PLGA NPs were prepared using modified emulsification-solvent evaporation technique and their characteristics were optimized by central composite experimental design in which average size, entrapment efficiency and drug loading were 170.5±11.87 nm, 77.35%±2.314 and 5.95%±0.087, respectively. Scanning electron microscopy and in vitro studies consisting of drug release and cytotoxicity in 4T1 breast cancer cells followed by in vivo biodistribution and blood cytotoxicity were carried out. Therapeutic efficacy of SN38-NPs was evaluated in xenograft balb/c animal with 4T1 breast cancer. The results demonstrated that the treatment with SN38-NPs was more efficacious in comparison with irinotecan. In conclusion, superior cytotoxic effect and improved in vivo antitumor efficacy of SN38-NPs versus irinotecan introduced SN38-NPs as a promising candidate for cancer treatment investigation. PMID:24879937

Sepehri, Nima; Rouhani, Hasti; Tavassolian, Faranak; Montazeri, Hamed; Khoshayand, Mohammad Reza; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Atyabi, Fatemeh; Dinarvand, Rassoul

2014-08-25

240

In vivo and in vitro evaluation of the cytotoxic effects of Photosan-loaded hollow silica nanoparticles on liver cancer  

NASA Astrophysics Data System (ADS)

This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions ( p < 0.05). Flow cytometry data demonstrated that laser-induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II ( p < 0.05). Activated caspase-3 and caspase-9 levels were significantly higher in cells treated with Photosan-II loaded in silica nanoparticles than free Photosan-II ( p < 0.05). Accordingly, treatment with nanoscale photosensitizers resulted in improved outcomes (tumor volume) in a mouse model of liver cancer, in comparison with conventional photosensitizers. Hollow silica nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro.

Liu, Zhong-Tao; Xiong, Li; Liu, Zhi-Peng; Miao, Xiong-Ying; Lin, Liang-Wu; Wen, Yu

2014-06-01

241

In vivo and in vitro evaluation of the cytotoxic effects of Photosan-loaded hollow silica nanoparticles on liver cancer  

PubMed Central

This study aimed to compare the inhibitory effects of photosensitizers loaded in hollow silica nanoparticles and conventional photosensitizers on HepG2 human hepatoma cell proliferation and determine the underlying mechanisms. Photosensitizers (conventional Photosan-II or nanoscale Photosan-II) were administered to in vitro cultured HepG2 hepatoma cells and treated by photodynamic therapy (PDT) with various levels of light exposure. To assess photosensitizers' effects, cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, apoptotic and necrotic cells were measured by flow cytometry and the expression of caspase-3 and caspase-9 evaluated by western blot. Finally, the in vivo effects of nanoscale and conventional photosensitizers on liver cancer were assessed in nude mice. Nanoscale Photosan-II significantly inhibited hepatoma cell viability in a concentration-dependent manner and this effect was more pronounced with high laser doses. Moreover, nanoscale photosensitizers performed better than the conventional ones under the same experimental conditions (p?induced cell death was markedly increased after treatment with nanoscale Photosan-II in comparison with free Photosan-II (p?nanoparticles than free Photosan-II (p?nanoparticles containing photosensitizer more efficiently inhibited hepatoma cells than photosensitizer alone, through induction of apoptosis, both in vivo and in vitro. PMID:25024681

2014-01-01

242

Targeting Activation Induced Cytidine Deaminase Overcome Tumor Evasion of Immunotherapy by Cytotoxic T Lymphocytes  

PubMed Central

Activation induced cytidine deaminase (AID) is an enzyme essential for the generation of antibody diversity in B cells and is considered to be a general gene mutator. In addition, AID expression was also implicated in the pathogenesis of human B cell malignancies and associated with poor prognosis. Here we report that siRNA silencing of AID in plasmacytoma dramatically increased its susceptibility to immunotherapy by cytotoxic T lymphocytes. AID silencing did not decrease the mutation frequencies of tumor antigen gene P1A. Gene-array analysis showed dramatically altered expression of a number of genes in AID-silenced plasmacytoma cells and upregulation of CD200 was shown to be in favor of tumor eradication by CTL. Taken together, we demonstrate a novel function of AID in tumor evasion of CTL therapy and that targeting AID should be beneficial in the immunotherapy of AID positive tumors. PMID:20404277

Liu, Jin-Qing; Joshi, Pramod S.; Wang, Chuansong; El-Omrani, Hani Y.; Xiao, Yi; Liu, Xiuping; Hagan, John P.; Liu, Chang-Gong; Wu, Lai-Chu; Bai, Xue-Feng

2010-01-01

243

Long-circulating poly(ethylene glycol)-grafted gelatin nanoparticles customized for intracellular delivery of noscapine: preparation, in-vitro characterization, structure elucidation, pharmacokinetics, and cytotoxicity analyses.  

PubMed

Noscapine, the tubulin-binding anticancer agent, when administered orally, requires high ED(50) (300-600 mg/kg), whereas intravenous administration (10 mg/kg) results in rapid elimination of the drug with a half-life of 0.39 h. Hence, the development of long-circulating injectable nanoparticles can be an interesting option for designing a viable formulation of noscapine for anticancer activity. Noscapine-enveloped gelatin nanoparticles and poly(ethylene glycol)-grafted gelatin nanoparticles were constructed and characterized. Data indicate that smooth and spherical shaped nanoparticles of 127 ± 15 nm were engineered with maximum entrapment efficiency of 65.32 ± 3.81%. Circular dichroism confirms that nanocoacervates retained the ?-helical content of gelatin in ethanol whereas acetone favored the formation of a random coil. Moreover, the Fourier transform infrared and powder X-ray diffraction pattern prevents any significant change in the noscapine-loaded gelatin nanoparticles in comparison with individual components. In-vitro release kinetic data suggest a first-order release of noscapine (85.1%) from gelatin nanoparticles with a release rate constant of 7.611×10(-3). It is to be noted that there is a 1.43-fold increase in the area under the curve up to the last sampling point for the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles over the noscapine-loaded gelatin nanoparticles and a 13.09-fold increase over noscapine. Cytotoxicity analysis of the MCF-7 cell line indicated that the IC(50) value of the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles was equivalent to 20.8 ?mol/l, which was significantly (P<0.05) lower than the IC(50) value of the noscapine-loaded gelatin nanoparticles (26.3 ?mol/l) and noscapine (40.5 ?mol/l).Noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles can be developed as a promising therapeutic agent for the management of breast cancer. PMID:21471809

Madan, Jitender; Dhiman, Neerupma; Sardana, Satish; Aneja, Ritu; Chandra, Ramesh; Katyal, Anju

2011-07-01

244

Cytotoxicity induced by nivalenol, deoxynivalenol, and fumonisin B1 in the SF-9 insect cell line.  

PubMed

The toxicity of the mycotoxins nivalenol (NIV), deoxynivalenol (DON), and fumonisin B1 (FB1) was studied in the lepidopteran Spodoptera frugiperda (SF-9) cells, by the trypan blue dye-exclusion and 3-(4,5-dimethylthiozole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) tests, uptake analyses of cytotoxicity, and cell metabolism, respectively. Deoxyribonucleic acid analysis by flow cytometry was used to identify apoptosis and cell cycle distribution. After 48 h of exposure, the MTT and trypan blue dye-exclusion tests indicated that NIV was significantly more toxic than DON, and both were significantly more toxic than FB1. The IC50 (mycotoxin concentration resulting in 50% inhibition of proliferation) values for NIV and DON were 4.5 and 41 microM, and the CC50 (mycotoxin concentration that caused 50% cytotoxicity) values were 9.5 and 45 microM, respectively. At the highest concentration of FB1 (100 microM), there was 80% viability. With the same incubation time, cell cycle distribution showed an arrest of cells in the G0/G1 phase in the presence of NIV (up to 0.3 microM), DON (up to 3 microM), and FB1 (up to 10 microM). Morphological evidence of apoptosis was related to the toxicity of the substances in that the more toxic NIV induced late apoptosis, whereas DON and FB1 produced less-severe morphological changes characteristic of early apoptosis. This study suggests that NIV is more toxic than DON, which in turn is more toxic than FB1. These mycotoxins can modify the normal progression of the cell cycle and induce an apoptotic process. PMID:15479121

Fornelli, Francesca; Minervini, Fiorenza; Mulè, Giuseppina

2004-01-01

245

Cytotoxic effects induced in vitro by organic extracts from urban air particulate matter in human leukocytes.  

PubMed

Urban areas represent major pollution sources as a result of anthropogenic activities located in these districts. Among the legislated air pollutants, polycyclic aromatic hydrocarbons (PAHs), which are mostly adsorbed on the surface of dust particles, are known for their adverse health effects. The present study has been carried out to examine the cytotoxic effects induced in vitro on human peripheral monocytes (PBMCs) by extractable organic matter (EOM) from PM10 (characterized for its PAH content) collected at four sites in the urban center of Messina, Italy. Chromatographic analyses showed the presence of PAHs in all EOM. Only EOM from one site induced a marked cell death probably resulting from the highest PAH content in this sample. Conversely, apoptosis activation was evident after PBMC exposure to all the EOM tested. These apoptotic effects do not appear related only to the total PAH content, but are probably influenced by chemical composition. In conclusion, our findings confirm that the cytotoxic potential of organic matter associated to ambient respirable air particles depends predominantly on the quantity and quality of the chemicals contained in it. In particular, the present data strongly evidence that the only evaluation of air concentration of particulate matter and benzo[a]pyrene, as well as the generally used risk models based on additivity, are not sufficient to evaluate air quality and PAH effect on human health because they do not take into account the possible inhibitory or synergic or antagonistic effect of combined exposure and the interference of other organic compounds present in respirable matter. PMID:24195653

Cimino, Francesco; Speciale, Antonio; Siracusa, Laura; Naccari, Clara; Saija, Antonella; Mancari, Ferdinando; Raciti, Roberto; Cristani, Mariateresa; Trombetta, Domenico

2014-01-01

246

The effects of conjugate and light dose on photo-immunotherapy induced cytotoxicity  

PubMed Central

Background Photoimmunotherapy (PIT) is a highly cell-selective cancer therapy, which employs monoclonal antibodies conjugated to a potent photosensitizer (mAb-IR700). Once the conjugate has bound to the target cell, exposure to near infrared (NIR) light induces necrosis only in targeted cells with minimal damage to adjacent normal cells in vivo. Herein, we report on the effect of altering mAb-IR700 and light power and dose on effectiveness of PIT. Methods For evaluating cytotoxicity, we employed ATP-dependent bioluminescence imaging using a luciferase-transfected MDA-MB-468luc cell line, which expresses EGFR and luciferase. In in vitro experiments, panitumumab-IR700 (Pan-IR700) concentration was varied in combination with varying NIR light doses administered by an LED at one of three power settings, 100 mA and 400 mA continuous wave and 1733 mA intermittent wave. For in vivo experiments, the MDA-MB-468luc orthotopic breast cancer was treated with varying doses of Pan-IR700 and light. Results The in vitro cell study demonstrated that PIT induced cytotoxicity depended on light dose, when the conjugate concentration was kept constant. Increasing the dose of Pan-IR700 allowed lowering of the light dose to achieve equal effects thus indicating that for a given level of efficacy, the conjugate concentration multiplied by the light dose was a constant. A similar relationship between conjugate and light dose was observed in vivo. Conclusions The efficacy of PIT is defined by the product of the number of bound antibody conjugates and the dose of NIR light and can be achieve equally with continuous and pulse wave LED light using different power densities. PMID:24885589

2014-01-01

247

Benthic cyanobacteria from the Baltic Sea contain cytotoxic Anabaena, Nodularia, and Nostoc strains and an apoptosis-inducing Phormidium strain.  

PubMed

Benthic cyanobacteria from aquatic environments have been reported to produce biologically active metabolites. However, the toxicity and other biological activities of benthic cyanobacteria from the Baltic Sea are not well known. We determined the biological activities of 21 Anabaena, Calothrix, Nodularia, Nostoc, and Phormidium strains isolated from benthic littoral habitats of the Baltic Sea. We studied whether benthic cyanobacterial extracts caused cytotoxicity by necrosis or induced apoptosis in two mammalian cell lines, a human leukemia cell line (HL-60) and a mouse fibroblast cell line (3T3 Swiss), and examined potential hepatotoxin (microcystin and nodularin) production. Five of the six benthic Anabaena strains, one of the two Nostoc strains, and two of the three Nodularia strains were highly cytotoxic to human leukemia cells. The Calothrix and Phormidium strains did not cause LDH leakage, but the extract of Phormidium strain BECID15 induced apoptosis in the HL-60 cells. Neither the microcystin synthetase E (mcyE) nor the nodularin synthetase F (ndaF) gene was amplified by PCR, and no microcystins or nodularins were detected by the protein phosphatase inhibition assay from the cyanobacterial strains included in this study. This indicates that benthic Baltic cyanobacteria contain potentially harmful cytotoxic compounds even though they do not produce microcystins or nodularins. These cytotoxic compounds remain to be characterized, and the mechanisms of cytotoxicity need to be studied further. PMID:15892066

Surakka, Anu; Sihvonen, Leila M; Lehtimäki, Jaana M; Wahlsten, Matti; Vuorela, Pia; Sivonen, Kaarina

2005-06-01

248

Unprecedented inhibition of tubulin polymerization directed by gold nanoparticles inducing cell cycle arrest and apoptosis.  

PubMed

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 ?10(5) 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 and safety of nanomaterials. PMID:23584723

Choudhury, Diptiman; Xavier, Paulrajpillai Lourdu; Chaudhari, Kamalesh; John, Robin; Dasgupta, Anjan Kumar; Pradeep, Thalappil; Chakrabarti, Gopal

2013-05-21

249

Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin's Lymphoma Cells  

PubMed Central

Autophagy is a critical mechanism in both cancer therapy resistance and tumor suppression. Monoclonal antibodies have been documented to kill tumor cells via apoptosis, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In this study, we report for the first time that chLym-1, a chimeric anti-human HLA-DR monoclonal antibody, induces autophagy in Raji Non-Hodgkin’s Lymphoma (NHL) cells. Interestingly, inhibition of autophagy by pharmacological inhibitors (3-methyladenine and NH4Cl) or genetic approaches (siRNA targeting Atg5) suppresses chLym-1-induced growth inhibition, apoptosis, ADCC and CDC in Raji cells, while induction of autophagy could accelerate cytotoxic effects of chLym-1 on Raji cells. Furthermore, chLym-1-induced autophagy can mediate apoptosis through Caspase 9 activation, demonstrating the tumor-suppressing role of autophagy in antilymphoma effects of chLym-1. Moreover, chLym-1 can activate several upstream signaling pathways of autophagy including Akt/mTOR and extracellular signal-regulated kinase 1/2 (Erk1/2). These results elucidate the critical role of autophagy in cytotoxicity of chLym-1 antibody and suggest a potential therapeutic strategy of NHL therapy by monoclonal antibody chLym-1 in combination with autophagy inducer. PMID:24015249

Li, Yubin; Wang, Shaofei; Wang, Ziyu; Sun, Yun; Gao, Hongjian; Zhang, Guoping; Feng, Meiqing; Ju, Dianwen

2013-01-01

250

S-adenosylmethionine but not glutathione protects against galactosamine-induced cytotoxicity in rat hepatocyte cultures.  

PubMed

A gradual but extensive depletion of hepatic GSH has long been known to accompany development of galactosamine-induced hepatotoxicity in rats, and some protection from liver injury has been observed after administration of sulfhydryl-donating compounds. Although these observations support a key role for GSH in the underlying mechanism, the impact of GSH depletion and repletion on the hepatotoxic response to galactosamine is unclear. To investigate the role of GSH in galactosamine-induced liver injury, we examined the effect of modulating GSH content on galactosamine toxicity in rat primary hepatocyte cultures. Galactosamine (4 mM) cytotoxicity was assessed by release of lactate dehydrogenase into the culture medium, and hepatocellular GSH content was measured by HPLC with electrochemical detection. The data indicated that prior depletion of GSH with either diethyl maleate or buthionine sulfoximine significantly enhanced galactosamine toxicity; however, addition of GSH-ester or alternate sulfur nucleophiles at various times during the incubation did not abrogate toxicity. In contrast, co-addition of S-adenosylmethionine (SAMe) with galactosamine exerted a marked protective effect without significantly altering hepatocyte GSH content. These data suggest that GSH depletion is not directly involved in the sequelae for galactosamine-induced hepatotoxicity, and raise the possibility that SAMe may have hepatoprotective effects that are not dependent on its ability to enhance GSH synthesis. PMID:16564122

McMillan, Joellyn M; McMillan, David C

2006-05-15

251

Cytoprotective and antioxidant activity of seabuckthorn (Hippophae rhamnoides L.) flavones against tert-butyl hydroperoxide-induced cytotoxicity in lymphocytes.  

PubMed

This study was designed to determine the cytoprotective activity of flavones of seabuckthorn (Hippophae rhamnoides L.) against tert-butyl hydroperoxide (tert-BOOH), used as an oxidant to induce oxidative damage, with lymphocytes as the model system. Addition of tert-BOOH (250 microM) to the cells resulted in enhanced cytotoxicity and free radical production. The intracellular calcium levels, caspase activity, and apoptosis were significantly increased following tert-BOOH treatment. Seabuckthorn flavones at the concentration of 100 microg/mL significantly inhibited tert-BOOH-induced cytotoxicity and free radical production and also restored the antioxidant status to that of control cells. Seabuckthorn flavones also significantly restricted tert-BOOH-induced apoptosis by decreasing intracellular calcium levels and caspase activity. The extract also decreased tert-BOOH-induced formation of DNA breaks by 30%. These observations suggest that the flavones of seabuckthorn have marked cytoprotective properties, which could be attributed to the antioxidant activity. PMID:19298209

Geetha, S; Ram, M Sai; Sharma, S K; Ilavazhagan, G; Banerjee, P K; Sawhney, R C

2009-02-01

252

Hypoxia-Induced Cytotoxic Drug Resistance in Osteosarcoma Is Independent of HIF-1Alpha  

PubMed Central

Survival rates from childhood cancer have improved dramatically in the last 40 years, such that over 80% of children are now cured. However in certain subgroups, including metastatic osteosarcoma, survival has remained stubbornly poor, despite dose intensive multi-agent chemotherapy regimens, and new therapeutic approaches are needed. Hypoxia is common in adult solid tumours and is associated with treatment resistance and poorer outcome. Hypoxia induces chemotherapy resistance in paediatric tumours including neuroblastoma, rhabdomyosarcoma and Ewing’s sarcoma, in vitro, and this drug resistance is dependent on the oxygen-regulated transcription factor hypoxia inducible factor-1 (HIF-1). In this study the effects of hypoxia on the response of the osteosarcoma cell lines 791T, HOS and U2OS to the clinically relevant cytotoxics cisplatin, doxorubicin and etoposide were evaluated. Significant hypoxia-induced resistance to all three agents was seen in all three cell lines and hypoxia significantly reduced drug-induced apoptosis. Hypoxia also attenuated drug-induced activation of p53 in the p53 wild-type U2OS osteosarcoma cells. Drug resistance was not induced by HIF-1? stabilisation in normoxia by cobalt chloride nor reversed by the suppression of HIF-1? in hypoxia by shRNAi, siRNA, dominant negative HIF or inhibition with the small molecule NSC-134754, strongly suggesting that hypoxia-induced drug resistance in osteosarcoma cells is independent of HIF-1?. Inhibition of the phosphoinositide 3-kinase (PI3K) pathway using the inhibitor PI-103 did not reverse hypoxia-induced drug resistance, suggesting the hypoxic activation of Akt in osteosarcoma cells does not play a significant role in hypoxia-induced drug resistance. Targeting hypoxia is an exciting prospect to improve current anti-cancer therapy and combat drug resistance. Significant hypoxia-induced drug resistance in osteosarcoma cells highlights the potential importance of hypoxia as a target to reverse drug resistance in paediatric osteosarcoma. The novel finding of HIF-1? independent drug resistance suggests however other hypoxia related targets may be more relevant in paediatric osteosarcoma. PMID:23785417

Adamski, Jennifer; Price, Andrew; Dive, Caroline; Makin, Guy

2013-01-01

253

Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A{sub 2}-induced degranulation in mast cells  

SciTech Connect

Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of {beta}-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G{sub M1}), di-sialoganglioside (G{sub D1a}) and tri-sialoganglioside (G{sub T1b}). In contrast, honeybee venom-derived phospholipase A{sub 2} induced the net degranulation directly without cytotoxicity, which was not inhibited by G{sub M1}, G{sub D1a} and G{sub T1b}. For analysis of distribution of G{alpha}{sub q} and G{alpha}{sub i} protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of G{alpha}{sub q} and G{alpha}{sub i} at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A{sub 2}-induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A{sub 2}-induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting.

Nishikawa, Hirofumi; Kitani, Seiichi, E-mail: drkitani@kaiyodai.ac.jp

2011-05-01

254

Assessment of cytotoxicity and oxidative effect of Bismuth Ferrite (BFO) harmonic nanoparticles for localized DNA photo-interaction  

NASA Astrophysics Data System (ADS)

Bismuth Ferrite nanoparticles have been recently used to selectively interact with malignant cell DNA via in situ generated second harmonic in a novel theranostics protocol [Nanoscale 6(5), pp. 2929, 2014]. In this report, we extend the screening of biocompatibility of BFO uncoated uncoated nanoparticles and assess the nanoparticle- mediated production of reactive oxygen species as a function of excitation wavelength.

Staedler, Davide; Magouroux, Thibaud; Passemard, Solène; Ciepielewski, Daniel; Gerber-Lemaire, Sandrine; Wolf, Jean-Pierre; Bonacina, Luigi

2014-09-01

255

Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin.  

PubMed

Ganoderma lucidum (G. lucidum) is a medicinal mushroom long used in Asia as a folk remedy to promote health and longevity. Recent studies indicate that G. lucidum activates NK cells, but the molecular mechanism underlying this effect has not been studied so far. To address this question, we prepared a water extract of G. lucidum and examined its effect on NK cells. We observed that G. lucidum treatment increases NK cell cytotoxicity by stimulating secretion of perforin and granulysin. The mechanism of activation involves an increased expression of NKG2D and natural cytotoxicity receptors (NCRs), as well as increased phosphorylation of intracellular MAPKs. Our results indicate that G. lucidum induces NK cell cytotoxicity against various cancer cell lines by activating NKG2D/NCR receptors and MAPK signaling pathways, which together culminate in exocytosis of perforin and granulysin. These observations provide a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans. PMID:23803412

Chang, Chih-Jung; Chen, Yi-Yuan M; Lu, Chia-Chen; Lin, Chuan-Sheng; Martel, Jan; Tsai, Sheng-Hui; Ko, Yun-Fei; Huang, Tsung-Teng; Ojcius, David M; Young, John D; Lai, Hsin-Chih

2014-04-01

256

Plasmon-induced hot carriers in metallic nanoparticles.  

PubMed

Plasmon-induced hot carrier formation is attracting an increasing research interest due to its potential for applications in photocatalysis, photodetection and solar energy harvesting. However, despite very significant experimental effort, a comprehensive theoretical description of the hot carrier generation process is still missing. In this work we develop a theoretical model for the plasmon-induced hot carrier process and apply it to spherical silver nanoparticles and nanoshells. In this model, the conduction electrons of the metal are described as free particles in a finite spherical potential well, and the plasmon-induced hot carrier production is calculated using Fermi’s golden rule. We show that the inclusion of many-body interactions has only a minor influence on the results. Using the model we calculate the rate of hot carrier generation, finding that it closely follows the spectral profile of the plasmon. Our analysis reveals that particle size and hot carrier lifetime play a central role in determining both the production rate and the energy distribution of the hot carriers. Specifically, larger nanoparticle sizes and shorter lifetimes result in higher carrier production rates but smaller energies, and vice versa. We characterize the efficiency of the hot carrier generation process by introducing a figure of merit that measures the number of high energy carriers generated per plasmon. Furthermore, we analyze the spatial distribution and directionality of these excitations. The results presented here contribute to the basic understanding of plasmon-induced hot carrier generation and provide insight for optimization of the process. PMID:24960573

Manjavacas, Alejandro; Liu, Jun G; Kulkarni, Vikram; Nordlander, Peter

2014-08-26

257

Protective and curative effects of Cocos nucifera inflorescence on alloxan-induced pancreatic cytotoxicity in rats  

PubMed Central

Objectives: This study was planned to investigate the effects of pre and post-treatment of young inflorescence of Cocos nucifera (CnI) on alloxan-induced diabetic rats. Materials and Methods: Male albino Sprague Dawely rats were divided into five groups of six animals each. Group I was normal control, Group II was diabetic control, Cocos nucifera Inflorescence (CnI) was fed along with diet [20% (w/w)] orally (Group III) for a period of 11 days prior to alloxan injection (150 mg/kg i.p.). The curative effect of CnI was evaluated at the same feeding levels in alloxan-induced diabetic rats (Group IV) for a period of 30 days. The effects of both pretreatment and post-treatment (Group V) were also evaluated. Biochemical parameters such serum glucose, hepatic glycogen, and enzymes involving carbohydrate metabolism (hexokinase, phosphoglucomutase, pyruvate kinase, glucose-6-phosphatase, fructose 1, 6-diphosphatase, glucose-6 phosphate dehydrogenase, and glycogen phosphorylase) were assayed along with pancreatic histopathology. Data were analyzed using one-way analysis of variance followed by Duncan's post hoc multiple variance test. P < 0.05 was considered statistical significant. Results: Diabetic control rats showed significant increase in serum glucose (P < 0.05) and decrease in hepatic glycogen levels (P < 0.05) compared to normal rats, which was reversed to near normal in both CnI pretreated and post-treated rats. Treatment with CnI resulted in significant decrease (P < 0.05) in activities of gluconeogenic enzymes in Group III and IV on compared to the diabetic control group, while glycolytic enzyme activities were improved in these groups. The cytotoxicity of pancreatic islets also ameliorated by treatment with CnI on histopathological examination. Conclusion: The results obtained in the study indicate the protective and curative effects of CnI on alloxan-induced pancreatic cytotoxicity, which is mediated through the regulation of carbohydrate metabolic enzyme activities and islets cell repair. PMID:23112412

Renjith, Raveendran S.; Rajamohan, Thankappan

2012-01-01

258

Stress-induced phase transformation and optical coupling of silver nanoparticle superlattices into mechanically stable nanowires  

NASA Astrophysics Data System (ADS)

One-dimensional silver materials display unique optical and electrical properties with promise as functional blocks for a new generation of nanoelectronics. To date, synthetic approaches and property engineering of silver nanowires have primarily focused on chemical methods. Here we report a simple physical method of metal nanowire synthesis, based on stress-induced phase transformation and sintering of spherical Ag nanoparticle superlattices. Two phase transformations of nanoparticles under stress have been observed at distinct length scales. First, the lattice dimensions of silver nanoparticle superlattices may be reversibly manipulated between 0-8?GPa compressive stresses to enable systematic and reversible changes in mesoscale optical coupling between silver nanoparticles. Second, stresses greater than 8?GPa induced an atomic lattice phase transformation, which induced sintering of silver nanoparticles into micron-length scale nanowires. The nanowire synthesis mechanism displays a dependence on both nanoparticle crystal surface orientation and presence of particular grain boundaries to enable nanoparticle consolidation into nanowires.

Li, Binsong; Wen, Xiaodong; Li, Ruipeng; Wang, Zhongwu; Clem, Paul G.; Fan, Hongyou

2014-06-01

259

Stress-induced phase transformation and optical coupling of silver nanoparticle superlattices into mechanically stable nanowires.  

PubMed

One-dimensional silver materials display unique optical and electrical properties with promise as functional blocks for a new generation of nanoelectronics. To date, synthetic approaches and property engineering of silver nanowires have primarily focused on chemical methods. Here we report a simple physical method of metal nanowire synthesis, based on stress-induced phase transformation and sintering of spherical Ag nanoparticle superlattices. Two phase transformations of nanoparticles under stress have been observed at distinct length scales. First, the lattice dimensions of silver nanoparticle superlattices may be reversibly manipulated between 0-8?GPa compressive stresses to enable systematic and reversible changes in mesoscale optical coupling between silver nanoparticles. Second, stresses greater than 8?GPa induced an atomic lattice phase transformation, which induced sintering of silver nanoparticles into micron-length scale nanowires. The nanowire synthesis mechanism displays a dependence on both nanoparticle crystal surface orientation and presence of particular grain boundaries to enable nanoparticle consolidation into nanowires. PMID:24957078

Li, Binsong; Wen, Xiaodong; Li, Ruipeng; Wang, Zhongwu; Clem, Paul G; Fan, Hongyou

2014-01-01

260

Cerium oxide nanoparticle-induced pulmonary inflammation and alveolar macrophage functional change in rats.  

PubMed

The use of cerium compounds as diesel fuel catalyst results in the emission of cerium oxide nanoparticles (CeO2) in the exhaust. This study characterized the potential effects of CeO2 exposure on lung toxicity. Male Sprague Dawley rats were exposed to CeO2 by a single intratracheal instillation at 0.15, 0.5, 1, 3.5 or 7 mg/kg body weight. At 1 day after exposure, CeO2 significantly reduced NO production, but increased IL-12 production, by alveolar macrophages (AM) in response to ex vivo lipopolysacchride (LPS) challenge, and caused AM apoptosis, through activation of caspases 9 and 3. CeO2 exposure markedly increased suppressor of cytokine signaling-1 at 1-day and elevated arginase-1 at 28-day post exposure in lung cells, while osteopontin was significantly elevated in lung tissue at both time points. CeO2 induced inflammation, cytotoxicity, air/blood barrier damage, and phospholipidosis with enlarged AM. Thus, CeO2 induced lung inflammation and injury in lungs which may lead to fibrosis. PMID:20925443

Ma, Jane Y; Zhao, Hongwen; Mercer, Robert R; Barger, Mark; Rao, Murali; Meighan, Terence; Schwegler-Berry, Diane; Castranova, Vincent; Ma, Joseph K

2011-09-01

261

Lymphocytes with cytotoxic activity induce rapid microtubule axonal destabilization independently and before signs of neuronal death  

PubMed Central

MS (multiple sclerosis) is the most prevalent autoimmune disease of the CNS (central nervous system) historically characterized as an inflammatory and demyelinating disease. More recently, extensive neuronal pathology has lead to its classification as a neurodegenerative disease as well. While the immune system initiates the autoimmune response it remains unclear how it orchestrates neuronal damage. In our previous studies, using in vitro cultured embryonic neurons, we demonstrated that MBP (myelin basic protein)-specific encephalitogenic CD4 T-cells induce early neuronal damage. In an extension of those studies, here we show that polarized CD4 Th1 and Th17 cells as wells as CD8 T-cells and NK (natural killer) cells induce microtubule destabilization within neurites in a contact-independent manner. Owing to the cytotoxic potential of these immune cells, we isolated the luminal components of lytic granules and determined that they were sufficient to drive microtubule destabilization. Since lytic granules contain cytolytic proteins, we determined that the induction of microtubule destabilization occurred prior to signs of apoptosis. Furthermore, we determined that microtubule destabilization was largely restricted to axons, sparing dendrites. This study demonstrated that lymphocytes with cytolytic activity have the capacity to directly drive MAD (microtubule axonal destabilization) in a bystander manner that is independent of neuronal death. PMID:23289514

Miller, Nichole M.; Shriver, Leah P.; Bodiga, Vijaya L.; Ray, Avijit; Basu, Sreemanti; Ahuja, Rajiv; Jana, Arundhati; Pahan, Kalipada; Dittel, Bonnie N.

2013-01-01

262

Protective effect of lipoic acid against acrolein-induced cytotoxicity in IMR-90 human fibroblasts.  

PubMed

Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the effects of acrolein on mitochondrial damage in IMR-90 (a human lung fibroblast cell line), and the reduction of this damage by R-alpha-lipoic acid were examined. Our results show that acute acrolein exposure exceeding 100 microM (24 h) in IMR-90 cells caused serious cytotoxicity, including decreases in cell viability, mitochondrial membrane potential, SOD activity, GSH and ATP levels, and acute exposure also increased in ROS levels. Pretreatment with R-alpha-lipoic acid effectively protected IMR-90 cells from acrolein toxicity. The results show that acrolein is a mitochondrial toxin in IMR-90 cells and that acrolein-induced oxidative mitochondrial dysfunction is reduced by R-alpha-lipoic acid. These experiments imply R-alpha-lipoic acid may be an effective antioxidant for reducing or preventing chronic oxidant-induced lung cells degeneration in vivo from a variety of sources, including cigarette smoke. PMID:19436138

Jia, Lihong; Zhang, Zhiyu; Zhai, Lingling; Bai, Yinglong

2009-04-01

263

Effect of vitamin C administration on hydrogen peroxide?induced cytotoxicity in periodontal ligament cells.  

PubMed

Periodontitis is a disease, which is associated with chronic inflammation and leads to significant destruction of periodontal tissues. Periodontal ligament cells (PDLCs) constitute the largest cell population in PDL tissues and a considerable body of evidence has demonstrated an association between oxidative stress and the progression of periodontitis. However, the effects on PDLCs exposed to hydrogen peroxide (H2O2) and the molecular mechanisms by which H2O2 affects periodontitis remain to be elucidated. In the present study, the potential cytotoxic effect of H2O2 and the antioxidative function of vitamin C (Vc) in PDLCs were investigated. The results demonstrated that H2O2 treatment decreased the viability of PDLCs. The decreased PDLC viability was primarily induced by apoptosis, which was evidenced by cleaved caspases?3, caspases?9 and poly (ADP?ribose) polymerase. Following optimal Vc addition, the proapoptotic effects of H2O2 were partially antagonized. Taken together, the present study demonstrated that H2O2 primarily induced the apoptosis of PDLCs and that these adverse effects were partially rescued following treatment with Vc. These results revealed how H2O2 promotes the progression of periodontitis and provide an improved understanding of the reversal effect of antioxidant treatment. Therefore, optimal Vc administration may provide a potentially effective technique in periodontal therapy. PMID:25333298

Wu, Wenlei; Yang, Nanfei; Feng, Xiujing; Sun, Tingzhe; Shen, Pingping; Sun, Weibin

2015-01-01

264

Determination and prevention of cytotoxic effects induced in human lymphocytes by the alkylating agent 2,2`-dichlorodiethyl sulfide (sulfur mustard, HD). (Reannouncement with new availability information)  

SciTech Connect

2,2`-Dichlorodiethyl sulfide (sulfur mustard), HD, 1,1`thiobis(2-chloroethane) is a potent vesicant which can cause severe lesions to skin, lung, and eyes. There is no convenient in vitro or in vivo method(s) to objectively measure the damage induced by HD; therefore, a simple in vitro method was developed using human peripheral lymphocytes to study HD-induced cytotoxicity. The cytotoxicity of HD was measured using dye exclusion as an indicator of human lymphocyte viability. Exposure to HD resulted in both a time- and a concentration-dependent cytotoxic effect on human lymphocytes. Using this in vitro assay, the effectiveness of various therapeutics (niacin, niacinamide, and 3-aminobenzamide) in preventing HD-induced cytotoxicity was studied. Niacinamide and 3-aminobenzamide prevented the cytotoxic effects of HD for up to 2 days.

Meier, H.L.; Johnson, J.B.

1992-12-31

265

Interaction and cytotoxic effects of hydrophobized chitosan nanoparticles on MDA-MB-231, HeLa and Arpe-19 cell lines.  

PubMed

In this work, we investigate the effect of chitosan hydrophobization on the internalization and cytotoxic effect of chitosan-based nanoparticles (NPs) on breast cancer cells (MDA-MB-231), cervical cancer cells (HeLa) and noncancer cells (Arpe-19). We also analyzed the interaction of NPs with a phospholipid (DPPC) membrane model at the airwater interface. An alkylation procedure to insert 8 carbon chains along the chitosan macromolecule with final 10 and 30 % substitution degrees was used. Nuclear magnetic resonance (NMR) and infrared spectroscopes (IR) were used to evaluate the success and extent of the hydrophobization procedure. Size, shape, and charge of NPs were evaluated by dynamic light scattering (DLS), atomic force microscope (AFM), and zeta potential, respectively. The effect of hydrophobicity on NPs was the reduction of the NPs average size, the formation of slightly elongated structures and the enhancing of the interaction of NPs with a DPPC monolayer at the air-water interface. By using fluorescence images on fluorescein-chitosan NPs, we observed a higher internalization of hydrophobic chitosan NPs in cancer cells in comparison with a low internalization of these NPs in normal cells. Even when non modified chitosan NPs were highly internalized in all cell lines, hydrophobized chitosan NPs showed a significantly higher cytotoxic effect on cancer cells in comparison with a lower effect showed by non-modified chitosan NPs on these cells. The cytotoxic effect on the normal cell line used was low for native chitosan NPs and negligible for hydrophobized chitosan NPs. PMID:24444157

Almada, Mario; Burboa, María G; Robles, Emmanuel; Gutiérrez, Luis E; Valdés, Miguel A; Juárez, Josué

2014-01-01

266

Aldehyde dehydrogenase 3A1 protects airway epithelial cells from cigarette smoke-induced DNA damage and cytotoxicity.  

PubMed

Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS). Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA levels showed the greatest induction in response to CS extract (CSE) exposure of primary human bronchial epithelial cells (HBECs). ALDH3A1 protein accumulation was accompanied by increased ALDH enzymatic activity in CSE-exposed immortalized HBECs. The effects of overexpression or suppression of ALDH3A1 on CSE-induced cytotoxicity and DNA damage (?H2AX) were evaluated in cultured immortalized HBECs. Enforced expression of ALDH3A1 attenuated cytotoxicity and downregulated ?H2AX. SiRNA-mediated suppression of ALDH3A1 blocked ALDH enzymatic activity and augmented cytotoxicity in CSE-exposed cells. Our results suggest that the availability of ALDH3A1 is important for cell survival against CSE in HBECs. PMID:24316006

Jang, Jun-Ho; Bruse, Shannon; Liu, Yushi; Duffy, Veronica; Zhang, Chunyu; Oyamada, Nathaniel; Randell, Scott; Matsumoto, Akiko; Thompson, David C; Lin, Yong; Vasiliou, Vasilis; Tesfaigzi, Yohannes; Nyunoya, Toru

2014-03-01

267

Micro-Raman Spectroscopy of Silver Nanoparticle Induced Stress on Optically-Trapped Stem Cells  

PubMed Central

We report here results of a single-cell Raman spectroscopy study of stress effects induced by silver nanoparticles in human mesenchymal stem cells (hMSCs). A high-sensitivity, high-resolution Raman Tweezers set-up has been used to monitor nanoparticle-induced biochemical changes in optically-trapped single cells. Our micro-Raman spectroscopic study reveals that hMSCs treated with silver nanoparticles undergo oxidative stress at doping levels in excess of 2 µg/ml, with results of a statistical analysis of Raman spectra suggesting that the induced stress becomes more dominant at nanoparticle concentration levels above 3 µg/ml. PMID:22514708

Bankapur, Aseefhali; Krishnamurthy, R. Sagar; Zachariah, Elsa; Santhosh, Chidangil; Chougule, Basavaraj; Praveen, Bhavishna; Valiathan, Manna; Mathur, Deepak

2012-01-01

268

Cell-mediated cytotoxicity of adherent and non-adherent mouse lymph node cells sensitized in vitro against tumour-associated antigens of syngenetic methylcholanthrene-induced sarcomas.  

PubMed

Cell-mediated cytotoxicity of adherent and non-adherent subpopulations of mouse lymph node cells sensitized in vitro on monolayers of syngeneic, methylcholanthrene-induced sarcoma cells was examined by inhibition of 3H-thymidine incorporation. The cell-mediated cytotoxicity of nylon wood-adherent, non-adherent and unfractionated lymph node cells was found to be equally efficient. PMID:456694

Indrová, M; Bubeník, J

1979-01-01

269

Mycobacterium tuberculosis Multidrug Resistant Strain M Induces an Altered Activation of Cytotoxic CD8+ T Cells  

PubMed Central

In human tuberculosis (TB), CD8+ T cells contribute to host defense by the release of Th1 cytokines and the direct killing of Mycobacterium tuberculosis (Mtb)-infected macrophages via granule exocytosis pathway or the engagement of receptors on target cells. Previously we demonstrated that strain M, the most prevalent multidrug-resistant (MDR) Mtb strain in Argentine, is a weak inducer of IFN-? and elicits a remarkably low CD8-dependent cytotoxic T cell activity (CTL). In contrast, the closely related strain 410, which caused a unique case of MDR-TB, elicits a CTL response similar to H37Rv. In this work we extend our previous study investigating some parameters that can account for this discrepancy. We evaluated the expressions of the lytic molecules perforin, granzyme B and granulysin and the chemokine CCL5 in CD8+ T cells as well as activation markers CD69 and CD25 and IL-2 expression in CD4+ and CD8+ T cells stimulated with strains H37Rv, M and 410. Our results demonstrate that M-stimulated CD8+ T cells from purified protein derivative positive healthy donors show low intracellular expression of perforin, granzyme B, granulysin and CCL5 together with an impaired ability to form conjugates with autologous M-pulsed macrophages. Besides, M induces low CD69 and IL-2 expression in CD4+ and CD8+ T cells, being CD69 and IL-2 expression closely associated. Furthermore, IL-2 addition enhanced perforin and granulysin expression as well as the degranulation marker CD107 in M-stimulated CD8+ T cells, making no differences with cells stimulated with strains H37Rv or 410. Thus, our results highlight the role of IL-2 in M-induced CTL activity that drives the proper activation of CD8+ T cells as well as CD4+ T cells collaboration. PMID:24836916

Geffner, Laura; Kviatcovsky, Denise; Sabio y García, Carmen; Ritacco, Viviana; López, Beatriz; Sasiain, María del Carmen; de la Barrera, Silvia

2014-01-01

270

Mycobacterium tuberculosis multidrug resistant strain M induces an altered activation of cytotoxic CD8+ T cells.  

PubMed

In human tuberculosis (TB), CD8+ T cells contribute to host defense by the release of Th1 cytokines and the direct killing of Mycobacterium tuberculosis (Mtb)-infected macrophages via granule exocytosis pathway or the engagement of receptors on target cells. Previously we demonstrated that strain M, the most prevalent multidrug-resistant (MDR) Mtb strain in Argentine, is a weak inducer of IFN-? and elicits a remarkably low CD8-dependent cytotoxic T cell activity (CTL). In contrast, the closely related strain 410, which caused a unique case of MDR-TB, elicits a CTL response similar to H37Rv. In this work we extend our previous study investigating some parameters that can account for this discrepancy. We evaluated the expressions of the lytic molecules perforin, granzyme B and granulysin and the chemokine CCL5 in CD8+ T cells as well as activation markers CD69 and CD25 and IL-2 expression in CD4+ and CD8+ T cells stimulated with strains H37Rv, M and 410. Our results demonstrate that M-stimulated CD8+ T cells from purified protein derivative positive healthy donors show low intracellular expression of perforin, granzyme B, granulysin and CCL5 together with an impaired ability to form conjugates with autologous M-pulsed macrophages. Besides, M induces low CD69 and IL-2 expression in CD4+ and CD8+ T cells, being CD69 and IL-2 expression closely associated. Furthermore, IL-2 addition enhanced perforin and granulysin expression as well as the degranulation marker CD107 in M-stimulated CD8+ T cells, making no differences with cells stimulated with strains H37Rv or 410. Thus, our results highlight the role of IL-2 in M-induced CTL activity that drives the proper activation of CD8+ T cells as well as CD4+ T cells collaboration. PMID:24836916

Geffner, Laura; Basile, Juan Ignacio; Yokobori, Noemí; Kviatcovsky, Denise; Sabio y García, Carmen; Ritacco, Viviana; López, Beatriz; Sasiain, María del Carmen; de la Barrera, Silvia

2014-01-01

271

Calcium channel blocker verapamil accelerates gambogic acid-induced cytotoxicity via enhancing proteasome inhibition and ROS generation.  

PubMed

Verapamil (Ver), an inhibitor of the multidrug resistance gene product, has been proved to be a promising combination partner with other anti-cancer agents including proteasome inhibitor bortezomib. Gambogic acid (GA) has been approved for Phase II clinical trials in cancer therapy in China. We have most recently reported that GA is a potent proteasome inhibitor, with anticancer efficiency comparable to bortezomib but much less toxicity. In the current study we investigated whether Ver can enhance the cytotoxicity of GA. We report that (i) the combination of Ver and GA results in synergistic cytotoxic effect and cell death induction in HepG2 and K562 cancer cell lines; (ii) a combinational treatment with Ver and GA induces caspase activation, endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production; (iii) caspase inhibitor z-VAD blocks GA+Ver-induced apoptosis but not proteasome inhibition; (iv) cysteine-containing compound N-acetylcysteine (NAC) prevents GA+Ver-induced poly(ADP-ribose) polymerase cleavage and proteasome inhibition. These results demonstrate that Ver accelerates GA-induced cytotoxicity via enhancing proteasome inhibition and ROS production. These findings indicate that the natural product GA is a valuable candidate that can be used in combination with Ver, thus representing a compelling anticancer strategy. PMID:24373880

Liu, Ningning; Huang, Hongbiao; Liu, Shouting; Li, Xiaofen; Yang, Changshan; Dou, Q Ping; Liu, Jinbao

2014-04-01

272

Clostridium perfringens Phospholipase C Induced ROS Production and Cytotoxicity Require PKC, MEK1 and NF?B Activation  

PubMed Central

Clostridium perfringens phospholipase C (CpPLC), also called ?-toxin, is the most toxic extracellular enzyme produced by this bacteria and is essential for virulence in gas gangrene. At lytic concentrations, CpPLC causes membrane disruption, whereas at sublytic concentrations this toxin causes oxidative stress and activates the MEK/ERK pathway, which contributes to its cytotoxic and myotoxic effects. In the present work, the role of PKC, ERK 1/2 and NF?B signalling pathways in ROS generation induced by CpPLC and their contribution to CpPLC-induced cytotoxicity was evaluated. The results demonstrate that CpPLC induces ROS production through PKC, MEK/ERK and NF?B pathways, the latter being activated by the MEK/ERK signalling cascade. Inhibition of either of these signalling pathways prevents CpPLC's cytotoxic effect. In addition, it was demonstrated that NF?B inhibition leads to a significant reduction in the myotoxicity induced by intramuscular injection of CpPLC in mice. Understanding the role of these signalling pathways could lead towards developing rational therapeutic strategies aimed to reduce cell death during a clostridialmyonecrosis. PMID:24466113

Monturiol-Gross, Laura; Flores-Diaz, Marietta; Pineda-Padilla, Maria Jose; Castro-Castro, Ana Cristina; Alape-Giron, Alberto

2014-01-01

273

Clostridium perfringens phospholipase C induced ROS production and cytotoxicity require PKC, MEK1 and NF?B activation.  

PubMed

Clostridium perfringens phospholipase C (CpPLC), also called ?-toxin, is the most toxic extracellular enzyme produced by this bacteria and is essential for virulence in gas gangrene. At lytic concentrations, CpPLC causes membrane disruption, whereas at sublytic concentrations this toxin causes oxidative stress and activates the MEK/ERK pathway, which contributes to its cytotoxic and myotoxic effects. In the present work, the role of PKC, ERK 1/2 and NF?B signalling pathways in ROS generation induced by CpPLC and their contribution to CpPLC-induced cytotoxicity was evaluated. The results demonstrate that CpPLC induces ROS production through PKC, MEK/ERK and NF?B pathways, the latter being activated by the MEK/ERK signalling cascade. Inhibition of either of these signalling pathways prevents CpPLC's cytotoxic effect. In addition, it was demonstrated that NF?B inhibition leads to a significant reduction in the myotoxicity induced by intramuscular injection of CpPLC in mice. Understanding the role of these signalling pathways could lead towards developing rational therapeutic strategies aimed to reduce cell death during a clostridialmyonecrosis. PMID:24466113

Monturiol-Gross, Laura; Flores-Díaz, Marietta; Pineda-Padilla, Maria Jose; Castro-Castro, Ana Cristina; Alape-Giron, Alberto

2014-01-01

274

Anti-CD2 and anti-CD3 induced T cell cytotoxicity of human intraepithelial and lamina propria lymphocytes.  

PubMed Central

The effector function of immunocompetent cells in the gut mucosa has not yet been defined. The cytotoxic function of these cells might be important in the normal immune response and could be relevant to the mucosal damage seen in inflammatory conditions. The cytotoxic function of isolated intraepithelial and lamina propria mononuclear cells in six and 18 hour assays after the addition of various stimuli that interact with the human leukocyte antigens CD2 and CD3 on the mucosal effector cells was investigated. T cell phenotypes were determined using CD4, CD8, and HML1 to characterise cells of the appropriate compartments. Anti-CD3 and phytohaemagglutinin can induce toxic activity of lamina propria lymphocytes in most individuals after six hours and in all individuals after 18 hours. Anti-CD2, anti-CD3, and phytohaemagglutinin are similarly effective at triggering lamina propria lymphocytes. Intraepithelial lymphocytes contain predominantly CD8 and HML1 positive T cells, differentiating phenotypically intraepithelial lymphocytes from lamina propria lymphocytes. Intraepithelial lymphocytes are not cytotoxic at six hours, but have a toxic function comparable with lamina propria lymphocytes after 18 hours with all three triggers. Intraepithelial lymphocytes from inflamed mucosa (Crohn's disease and diverticulitis) mediate significantly reduced cytotoxicity in vitro compared with normal mucosa, whereas lamina propria lymphocyte toxicity is not different. Reduced numbers of cytotoxic cells and reduced reactivity to the trigger substances used after in vivo activation or cold target inhibition could explain the observed differences between intraepithelial lymphocytes from inflamed and uninflamed mucosa. Changes in cell mediated cytotoxicity of intraepithelial lymphocytes and lamina propria lymphocytes may be involved in the mucosal damage in these inflammatory conditions. PMID:1362554

Ruthlein, J; Heinze, G; Auer, I O

1992-01-01

275

In situ nanoparticle size measurements of gas-borne silicon nanoparticles by time-resolved laser-induced incandescence  

NASA Astrophysics Data System (ADS)

This paper describes the application of time-resolved laser-induced incandescence (TiRe-LII), a combustion diagnostic used mainly for measuring soot primary particles, to size silicon nanoparticles formed within a plasma reactor. Inferring nanoparticle sizes from TiRe-LII data requires knowledge of the heat transfer through which the laser-heated nanoparticles equilibrate with their surroundings. Models of the free molecular conduction and evaporation are derived, including a thermal accommodation coefficient found through molecular dynamics. The model is used to analyze TiRe-LII measurements made on silicon nanoparticles synthesized in a low-pressure plasma reactor containing argon and hydrogen. Nanoparticle sizes inferred from the TiRe-LII data agree with the results of a Brunauer-Emmett-Teller analysis.

Sipkens, T. A.; Mansmann, R.; Daun, K. J.; Petermann, N.; Titantah, J. T.; Karttunen, M.; Wiggers, H.; Dreier, T.; Schulz, C.

2014-09-01

276

Multigenerational study of chemically induced cytotoxicity and proliferation in cultures of human proximal tubular cells.  

PubMed

Primary cultures of human proximal tubular (hPT) cells are a useful experimental model to study transport, metabolism, cytotoxicity, and effects on gene expression of a diverse array of drugs and environmental chemicals because they are derived directly from the in vivo human kidney. To extend the model to investigate longer-term processes, primary cultures (P0) were passaged for up to four generations (P1-P4). hPT cells retained epithelial morphology and stained positively for cytokeratins through P4, although cell growth and proliferation successively slowed with each passage. Necrotic cell death due to the model oxidants tert-butyl hydroperoxide (tBH) and methyl vinyl ketone (MVK) increased with increasing passage number, whereas that due to the selective nephrotoxicant S-(1,2-dichlorovinyl)-l-cysteine (DCVC) was modest and did not change with passage number. Mitochondrial activity was lower in P2-P4 cells than in either P0 or P1 cells. P1 and P2 cells were most sensitive to DCVC-induced apoptosis. DCVC also increased cell proliferation most prominently in P1 and P2 cells. Modest differences with respect to passage number and response to DCVC exposure were observed in expression of three key proteins (Hsp27, GADD153, p53) involved in stress response. Hence, although there are some modest differences in function with passage, these results support the use of multiple generations of hPT cells as an experimental model. PMID:25411799

Lash, Lawrence H; Putt, David A; Benipal, Bavneet

2014-01-01

277

Investigation of the cytotoxic, genotoxic, and apoptosis-inducing effects of estragole isolated from fennel (Foeniculum vulgare).  

PubMed

The present study was undertaken to evaluate, in the HepG2 human hepatoma cell line, the in vitro cytotoxic, genotoxic, and apoptotic activities of estragole (1), contained in the essential oil of Foeniculum vulgare (fennel) and suspected to induce hepatic tumors in susceptible strains of mice. Toward this end, an MTT cytotoxicity assay, a trypan blue dye exclusion test, a double-staining (acridine orange and DAPI) fluorescence viability assay, a single-cell microgel-electrophoresis (comet) assay, a mitochondrial membrane potential (??m) assay, and a DNA fragmentation analysis were conducted. In terms of potential genotoxic effects, the comet assay indicated that estragole (1) was not able to induce DNA damage nor apoptosis under the experimental conditions used. PMID:24617303

Villarini, Milena; Pagiotti, Rita; Dominici, Luca; Fatigoni, Cristina; Vannini, Samuele; Levorato, Sara; Moretti, Massimo

2014-04-25

278

Inducement of specific CTLs by antigen-peptides from human leukemia cells and their cytotoxicity to leukemia cells  

Microsoft Academic Search

Summary  To investigate the inducement of cytotoxic T lymphocytes (CTLs) by antigen peptides mixture from different leukemia cells\\u000a and the cross-reaction of the mixtures from different cell lines, antigen peptides mixtures were prepared from different leukemia\\u000a cell lines respectively and then bound with Hsp70in vitro. Activation and proliferation of PBMC were observed after stimulation with different Hsp70-peptide complexes. The ratio of

Zuohua Feng; Guimei Zhang; Bo Huang; Dong Li; Hongtao Wang

2002-01-01

279

Identification of potentially cytotoxic lesions induced by UVA photoactivation of DNA 4-thiothymidine in human cells.  

PubMed

Photochemotherapy-in which a photosensitizing drug is combined with ultraviolet or visible radiation-has proven therapeutic effectiveness. Existing approaches have drawbacks, however, and there is a clinical need to develop alternatives offering improved target cell selectivity. DNA substitution by 4-thiothymidine (S(4)TdR) sensitizes cells to killing by ultraviolet A (UVA) radiation. Here, we demonstrate that UVA photoactivation of DNA S(4)TdR does not generate reactive oxygen or cause direct DNA breakage and is only minimally mutagenic. In an organotypic human skin model, UVA penetration is sufficiently robust to kill S(4)TdR-photosensitized epidermal cells. We have investigated the DNA lesions responsible for toxicity. Although thymidine is the predominant UVA photoproduct of S(4)TdR in dilute solution, more complex lesions are formed when S(4)TdR-containing oligonucleotides are irradiated. One of these, a thietane/S(5)-(6-4)T:T, is structurally related to the (6-4) pyrimidine:pyrimidone [(6-4) Py:Py] photoproducts induced by UVB/C radiation. These lesions are detectable in DNA from S(4)TdR/UVA-treated cells and are excised from DNA more efficiently by keratinocytes than by leukaemia cells. UVA irradiation also induces DNA interstrand crosslinking of S(4)TdR-containing duplex oligonucleotides. Cells defective in repairing (6-4) Py:Py DNA adducts or processing DNA crosslinks are extremely sensitive to S(4)TdR/UVA indicating that these lesions contribute significantly to S(4)TdR/UVA cytotoxicity. PMID:21890905

Reelfs, Olivier; Macpherson, Peter; Ren, Xiaolin; Xu, Yao-Zhong; Karran, Peter; Young, Antony R

2011-12-01

280

Discrete nanoparticles induce loss of Legionella pneumophila biofilms from surfaces.  

PubMed

Nanoparticles (NPs) have been shown to induce dispersal events in microbial biofilms but the mechanism of the dispersal is unknown. Biofilms contaminate many man-made aquatic systems such as cooling towers, spas and dental lines. Within these biofilms, Legionella pneumophila is a primary pathogen, leading to these environments serving as sources for disease outbreaks. Here we show a reduction in biofilm bio-volume upon treatment with citrate-coated 6-nm platinum NPs, polyethylene glycol (PEG)-coated 11-nm gold NPs, and PEG-coated 8-nm iron oxide NPs. Treatment with citrate-coated 8-nm silver NPs, however, did not reduce biomass. The synthesis of NPs that remain dispersed and resist irreversible aggregation in the exposure media appears to be a key factor in the ability of NPs to induce biofilm dispersal. PMID:23586422

Raftery, Tara D; Kerscher, Petra; Hart, Ashley E; Saville, Steven L; Qi, Bin; Kitchens, Christopher L; Mefford, Olin Thompson; McNealy, Tamara L

2014-08-01

281

Urethane dimethacrylate induces cytotoxicity and regulates cyclooxygenase-2, hemeoxygenase and carboxylesterase expression in human dental pulp cells.  

PubMed

The toxic effect of urethane dimethacrylate (UDMA), a major dental resin monomer, on human dental pulp is not fully clear. In this study, we investigated the influence of UDMA on the cytotoxicity, cell cycle distribution, apoptosis and related gene expression of dental pulp cells. The role of reactive oxygen species, hemeoxygenase-1 (HO-1) and carboxylesterase (CES) in UDMA cytotoxicity, was evaluated. UDMA induced morphological changes of pulp cells and decreased cell viability by 29-49% at concentrations of 0.1-0.35 mM. UDMA induced G0/G1, G2/M cell cycle arrest and apoptosis. The expression of cdc2, cyclinB1 and cdc25C was inhibited by UDMA. Moreover, UDMA stimulated COX-2, HO-1 and CES2 mRNA expression of pulp cells. The cytotoxicity of UDMA was attenuated by N-acetyl-l-cysteine, catalase and esterase, but was enhanced by Zn-protoporphyrin (HO-1 inhibitor), BNPP (CES inhibitor) and loperamide (CES2 inhibitor). Exposure of UDMA may potentially induce the inflammation and toxicity of dental pulp. These findings are important for understanding the clinical response of human pulp to resin monomers after operative restoration and pulp capping, and also provide clues for improvement of dental materials. PMID:24140606

Chang, Hsiao-Hua; Chang, Mei-Chi; Wang, Hsin-Hui; Huang, Guay-Fen; Lee, Yuan-Ling; Wang, Yin-Lin; Chan, Chiu-Po; Yeung, Sin-Yuet; Tseng, Shuei-Kuen; Jeng, Jiiang-Huei

2014-02-01

282

Mechanisms of nanoparticle-induced oxidative stress and toxicity.  

PubMed

The rapidly emerging field of nanotechnology has offered innovative discoveries in the medical, industrial, and consumer sectors. The unique physicochemical and electrical properties of engineered nanoparticles (NP) make them highly desirable in a variety of applications. However, these novel properties of NP are fraught with concerns for environmental and occupational exposure. Changes in structural and physicochemical properties of NP can lead to changes in biological activities including ROS generation, one of the most frequently reported NP-associated toxicities. Oxidative stress induced by engineered NP is due to acellular factors such as particle surface, size, composition, and presence of metals, while cellular responses such as mitochondrial respiration, NP-cell interaction, and immune cell activation are responsible for ROS-mediated damage. NP-induced oxidative stress responses are torch bearers for further pathophysiological effects including genotoxicity, inflammation, and fibrosis as demonstrated by activation of associated cell signaling pathways. Since oxidative stress is a key determinant of NP-induced injury, it is necessary to characterize the ROS response resulting from NP. Through physicochemical characterization and understanding of the multiple signaling cascades activated by NP-induced ROS, a systemic toxicity screen with oxidative stress as a predictive model for NP-induced injury can be developed. PMID:24027766

Manke, Amruta; Wang, Liying; Rojanasakul, Yon

2013-01-01

283

In vitro evaluation of cellular responses induced by ZnO nanoparticles, zinc ions and bulk ZnO in fish cells.  

PubMed

Zinc oxide nanoparticles (ZnO-NPs) are inevitably released into the environment and are potentially dangerous for aquatic life. However, the potential mechanisms of cytotoxicity of zinc nanoparticles remain unclear. Studying the toxicity of ZnO-NPs with In vitro systems will help to determine their interactions with cellular biomolecules. The aim of this study was to evaluate the cytotoxic potentials of ZnO-NPs in established fish cell lines (RTG-2, RTH-149 and RTL-W1) and compare them with those of bulk ZnO and Zn(2+) ions. Membrane function (CFDA-AM assay), mitochondrial function (MTT assay), cell growth (KBP assay), cellular stress (?-galactosidase assay), reductase enzyme activity (AB assay), reactive oxygen species (ROS), total glutathione cellular content (tGSH assay) and glutathione S-transferase (GST) activities were assessed for all cell lines. ZnO-NPs cytotoxicity was greater than those of bulk ZnO and Zn(2+). ZnO-NPs induced oxidative stress is dependent on their dose. Low cost tests, such as CFDA-AM, ROS, GST activity and tGSH cell content test that use fish cell lines, may be used to detect oxidative stress and redox status changes. Particle dissolution of the ZnO-NPs did not appear to play an important role in the observed toxicity in this study. PMID:23523724

Fernández, Dolores; García-Gómez, Concepción; Babín, Mar

2013-05-01

284

Structural responses of cells to intracellular magnetic force induced by superparamagnetic iron oxide nanoparticles.  

PubMed

In this paper, we study the effects of intracellular force on human umbilical vein endothelial cells. We generated intracellular force on endothelial cells under different magnetic fields using the cell uptake of superparamagnetic iron oxide nanoparticles. Cell responses to intracellular force were observed using fluorescent microscopy. Our results indicated that nanoparticles were taken up by the cell by endocytosis and were deposited in lysosomes. Nanoparticles and lysosomes inside the cell could be relocated by the application of a magnetic force. The intracellular magnetic force could also be used to accelerate cell migration by adjusting the magnetic fields and giving the cell free culture space. No cytotoxicity of nanoparticles was found in our experiments. By comparing intracellular relocalization with migration of the whole cell, we obtained a better understanding of the self-defence mechanisms of cells based on their mechanical properties. Based on the promising mechanical properties and low cytotoxicity of our magnetic nanoparticles, their potential applications in cytomechanics and cell patterning are discussed. PMID:24336693

Shen, Han; Tong, Sheng; Bao, Gang; Wang, Biao

2014-02-01

285

Zinc oxide nanoparticles selectively induce apoptosis in human cancer cells through reactive oxygen species  

PubMed Central

Background Zinc oxide nanoparticles (ZnO NPs) have received much attention for their implications in cancer therapy. It has been reported that ZnO NPs induce selective killing of cancer cells. However, the underlying molecular mechanisms behind the anticancer response of ZnO NPs remain unclear. Methods and results We investigated the cytotoxicity of ZnO NPs against three types of cancer cells (human hepatocellular carcinoma HepG2, human lung adenocarcinoma A549, and human bronchial epithelial BEAS-2B) and two primary rat cells (astrocytes and hepatocytes). Results showed that ZnO NPs exert distinct effects on mammalian cell viability via killing of all three types of cancer cells while posing no impact on normal rat astrocytes and hepatocytes. The toxicity mechanisms of ZnO NPs were further investigated using human liver cancer HepG2 cells. Both the mRNA and protein levels of tumor suppressor gene p53 and apoptotic gene bax were upregulated while the antiapoptotic gene bcl-2 was downregulated in ZnO NP-treated HepG2 cells. ZnO NPs were also found to induce activity of caspase-3 enzyme, DNA fragmentation, reactive oxygen species generation, and oxidative stress in HepG2 cells. Conclusion Overall, our data demonstrated that ZnO NPs selectively induce apoptosis in cancer cells, which is likely to be mediated by reactive oxygen species via p53 pathway, through which most of the anticancer drugs trigger apoptosis. This study provides preliminary guidance for the development of liver cancer therapy using ZnO NPs. PMID:22393286

Akhtar, Mohd Javed; Ahamed, Maqusood; Kumar, Sudhir; Khan, MA Majeed; Ahmad, Javed; Alrokayan, Salman A

2012-01-01

286

Genotoxicity of silver nanoparticles in Allium cepa  

Microsoft Academic Search

Potential health and environmental effects of nanoparticles need to be thoroughly assessed before their widespread commercialization. Though there are few studies on cytotoxicity of nanoparticles on mammalian and human cell lines, there are hardly any reports on genotoxic and cytotoxic behavior of nanoparticles in plant cells. This study aims to investigate cytotoxic and genotoxic impacts of silver nanoparticles using root

Mamta Kumari; A. Mukherjee; N. Chandrasekaran

2009-01-01

287

Selenium-containing analogs of SAHA induce cytotoxicity in lung cancer cells.  

PubMed

Cancer therapy has moved beyond conventional chemotherapeutics to more mechanism-based targeted approaches. Studies demonstrate that histone deacetylase (HDAC) is a promising target for anticancer agents. Numerous, structurally diverse, hydroxamic acid derivative, HDAC inhibitors have been reported and have been shown to induce growth arrest, differentiation, autophagy, and/or apoptotic cell death by inhibiting multiple signaling pathways in cancer cells. Suberoylanilide hydroxamic acid (SAHA) has emerged as an effective anticancer therapeutic agent and was recently approved by the FDA for the treatment of advanced cutaneous T-cell lymphoma. In our previous study, we reported the development of the novel, potent, selenium-containing HDAC inhibitors (SelSA-1 and SelSA-2). In this study, the effects of SelSA-1 and SelSA-2 on signaling pathways and cytotoxicity were compared with the known HDAC inhibitor, SAHA, in lung cancer cell lines. After 24 h of treatment, SelSA-1 and SelSA-2 inhibited lung cancer cell growth to a greater extent than SAHA in a dose-dependent manner with IC(50) values at low micromolar concentrations. SelSA-1 and SelSA-2 inhibited ERK and PI3K-AKT signaling pathways while simultaneously increasing in autophagy in A549 cells in a time dependent manner. This preliminary study demonstrates the effectiveness of the selenium-containing analogs of SAHA, SelSA-1, and SelSA-2, as HDAC inhibitors and provides insight into the improvement and/or development of these analogs as a therapeutic approach for the treatment of lung cancer. PMID:20855208

Karelia, Nilkamal; Desai, Dhimant; Hengst, Jeremy A; Amin, Shantu; Rudrabhatla, Sairam V; Yun, Jong

2010-11-15

288

Selenium-Containing Analogs of SAHA Induce Cytotoxicity in Lung Cancer Cells  

PubMed Central

Cancer therapy has moved beyond conventional chemotherapeutics to more mechanism-based targeted approaches. Studies demonstrate that histone deacetylase (HDAC) is a promising target for anticancer agents. Numerous, structurally diverse, hydroxamic acid derivative, HDAC inhibitors have been reported and have been shown to induce growth arrest, differentiation, autophagy and/or apoptotic cell death by inhibiting multiple signaling pathways in cancer cells. Suberoylanilide hydroxamic acid (SAHA) has emerged as an effective anticancer therapeutic agent and was recently approved by the FDA for the treatment of advanced cutaneous T- cell lymphoma. In our previous study, we reported the development of the novel, potent, selenium containing HDAC inhibitors (SelSA-1 and SelSA-2). In this study, the effects of SelSA-1 and SelSA-2 on signaling pathways and cytotoxicity were compared with the known HDAC inhibitor, SAHA, in lung cancer cell lines. After 24 hours of treatment, SelSA-1 and SelSA-2 inhibited lung cancer cell growth to a greater extent than SAHA in a dose-dependent manner with IC50 values at low micromolar concentrations. SelSA-1 and SelSA-2 inhibited ERK and PI3K-AKT signaling pathways while simultaneously increasing in autophagy in A549 cells in a time dependent manner. This preliminary study demonstrates the effectiveness of the selenium-containing analogs of SAHA, SelSA-1 and SelSA-2, as HDAC inhibitors and provides insight into the improvement and/or development of these analogs as a therapeutic approach for the treatment of lung cancer. PMID:20855208

Karelia, Nilkamal; Desai, Dhimant; Hengst, Jeremy A.; Amin, Shantu; Rudrabhatla, Sairam V.; Yun, Jong

2010-01-01

289

POLYCHLORINATED BIPHENYL (PCB)-INDUCED OXIDATIVE STRESS AND CYTOTOXICITY CAN BE MITIGATED BY ANTIOXIDANTS FOLLOWING EXPOSURE  

PubMed Central

PCBs and PCB metabolites have been suggested to cause cytotoxicity by inducing oxidative stress but the effectiveness of antioxidant intervention following exposure is not established. Exponentially growing MCF-10A human breast and RWPE-1 human prostate epithelial cells continuously exposed for 5 days to 3 ?M PCBs [Aroclor 1254, PCB153, and the 2-(4-chlorophenyl)-1,4-benzoquinone metabolite of PCB3 (4ClBQ)] were found to exhibit growth inhibition and clonogenic cell killing, with 4ClBQ having the most pronounced effects. These PCBs were also found to increase steady-state levels intracellular O2·? and H2O2 (as determined by dihydroethidium, MitoSOX™red and 5-(and-6)-carboxy-2?,7?-dichlorodihydrofluorescein diacetate oxidation). These PCBs also caused 1.5- to 5.0-fold increases in MnSOD activity in MCF-10A cells and 2.5- to 5-fold increases in CuZnSOD activity in RWPE-1 cells. Measurement of MitoSOX™red oxidation with confocal microscopy coupled with co-localization of MitoTracker green in MCF-10A and RWPE-1 cells, supported the hypothesis that PCBs caused increased steady-state levels of O2·? in mitochondria. Finally, treatment with either N-acetyl-cysteine (NAC), or the combination of polyethylene glycol (PEG) conjugated CuZnSOD and PEG-catalase added 1 hour after PCBs, significantly protected these cells from PCB toxicity. These results support the hypothesis that exposure of exponentially growing human breast and prostate epithelial cells to PCBs causes increased steady-state levels of intracellular O2·? and H2O2, induction of MnSOD or CuZnSOD activities, as well as clonogenic cell killing that could be inhibited by a clinically relevant thiol antioxidant, NAC, as well as by catalase and superoxide dismutase following PCB exposure. PMID:19796678

Zhu, Yueming; Kalen, Amanda L.; Li, Ling; Lehmler, Hans-J; Robertson, Larry W.; Goswami, Prabhat C.; Spitz, Douglas R.; Aykin-Burns, Nukhet

2009-01-01

290

Decreased helenalin-induced cytotoxicity by flavonoids from Arnica as studied in a human lung carcinoma cell line.  

PubMed

The effect of the flavones apigenin, luteolin, hispidulin and eupafolin, and of the flavonols kaempferol, quercetin, 6-methoxykaempferol and patuletin from Arnica spp. on the cytotoxicity of the sesquiterpene lactone helenalin was studied in the human lung carcinoma cell line GLC4 using the microculture tetrazolium (MTT) assay. The tumour cells were exposed to the test compounds for 2h. Helenalin concentrations around its control IC(50) value, 0.5 ?M, were combined with flavonoid concentrations ranging from 0.01 to 20 ?M. At non-toxic concentrations, up to 10?M, all flavonoids except kaempferol significantly reduced the helenalin-induced cytotoxicity. Hispidulin and patuletin displayed their modulating effect on helenalin-induced cytotoxicity in the broadest concentration range. The strongest effect was found with 5 and 10?M hispidulin, 0.05 ?M quercetin, and 1 ?M patuletin, increasing the IC(50) value of helenalin with circa 40%. No dose-dependency was found in the concentration range tested. PMID:23196154

Woerdenbag, H J; Merfort, I; Schmidt, T J; Passreiter, C M; Willuhn, G; Van Uden, W; Pras, N; Konings, A W

1995-10-01

291

Genotoxicity of copper oxide and silver nanoparticles in the mussel Mytilus galloprovincialis.  

PubMed

Though there is some information on cytotoxicity of copper nanoparticles and silver nanoparticles on human cell lines, there is no information on their genotoxic and cytotoxic behaviour in bivalve molluscs. The aim of this study was to investigate the genotoxic impact of copper oxide and silver nanoparticles using mussels Mytilus galloprovincialis. Mussels were exposed to 10 ?g L?¹ of CuO nanoparticles and Cu²? and Ag nanoparticles and Ag? for 15 days to assess genotoxic effects in hemocytes using the comet assay. The results obtained indicated that copper and silver forms (nanoparticles and ionic) induced DNA damage in hemolymph cells and a time-response effect was evident when compared to unexposed mussels. Ionic forms presented higher genotoxicity than nanoparticles, suggesting different mechanisms of action that may be mediated through oxidative stress. DNA strand breaks proved to be a useful biomarker of exposure to genotoxic effects of CuO and Ag nanoparticles in marine molluscs. PMID:23294529

Gomes, Tânia; Araújo, Olinda; Pereira, Rita; Almeida, Ana C; Cravo, Alexandra; Bebianno, Maria João

2013-03-01

292

Novel application of the CORAL software to model cytotoxicity of metal oxide nanoparticles to bacteria Escherichia coli  

E-print Network

studies of nanomaterials, such as the metal oxide nanoparticles (Puzyn et al., 2011) fullerene C60 (Toropova et al., 2010; Toropov et al., 2010a,b), and C70 (Toropova et al., 2011) become an integral part

Gini, Giuseppina

293

Hierarchical nanoparticle clusters induced by block copolymer self-assembly.  

PubMed

The hierarchical relation of microscale structures with those of zoomed-in nanoscale in a composite material is one of the challenging issues. In terms of multiscale regional analogy of fractal, identical motifs are repeated on different size scales. However, idealized packing schemes are typically known to break down beyond a length scale of a few clusters. Here, we propose a new packing scheme - the structural analogy investigated by gold nanoparticle (AuNP) clusters describes a deformed self-similarity in multiscales. The clusters are directly imaged in microscale and in submicroscale using X-ray microscopy (XM) and X-ray nanoscopy (XN) without sample distortion in the hierarchical field-of-view up to 600 ?m. We show that the broad-range ordering has the characteristics of a fractal with a dimension (D) between 1 and 2. This D value is smaller in XN scale than in XM scale, indicating dense cluster formation in large scale. The D values are independent from the pathways of cluster growth and compatibility of AuNPs with the polymer template. The nanoparticle cluster growth induced by block copolymer self-assembly is characteristically different from those occurring in free-space where the conventional diffusion- or reaction-limited aggregations are dominant. Our findings provide a new perspective in organic-inorganic hybrid nanomaterials and has broad implications in understanding their structure-property relationship for various applications. PMID:24797284

Ahn, Sungsook; Lee, Sang Joon

2014-06-14

294

Quercetin-3-O-?-D-glucopyranoside, a dietary flavonoid, protects PC12 cells from H?O?-induced cytotoxicity through inhibition of reactive oxygen species.  

PubMed

Since flavonols are antioxidant agents, they could in principle, beneficially affect neurodegenerative diseases where reactive oxygen species are involved. Quercetin derivatives are the most abundant dietary flavonoids, and we have investigated the capacity of quercetin-3-O-?-d-glucopyranoside (Q3G) isolated from Echinophora cinerea to protect PC12 cells from H2O2-induced cytotoxicity. Direct cytotoxic effects of H2O2 on PC12 in presence and absence of Q3G were evaluated. H2O2 induced cytotoxicity in a concentration dependent manner (IC50=118 ± 5.09 ?M, 24h). Pretreatment of cells with non-toxic concentrations of Q3G protected cells from H2O2-induced cytotoxicity, leading to a decrease in the generation of reactive oxygen species. These observations qualify Q3G as an interesting dietary compound worth further investigation as a cytoprotective agent. PMID:25148973

Shokoohinia, Yalda; Rashidi, Maryam; Hosseinzadeh, Leila; Jelodarian, Zohreh

2015-01-15

295

Water induced protonation of amine-terminated micelles for direct syntheses of ZnO quantum dots and their cytotoxicity towards cancer  

NASA Astrophysics Data System (ADS)

This work designs a new strategy for the direct synthesis of different zinc oxide (ZnO) nanostructures at low temperatures. Micelles of dodecylamine (DDA) assembled in an ethanol-water system have been explored as a template to direct the growth of the ZnO nanostructures. The key species for the formation of the ZnO nanostructures, OH-, can be provided by the water-induced protonation of DDA. The pH of the reaction micro-environment can be regulated by changing the input amount of water and DDA. By controlling the reaction temperature and pH, various ZnO nanostructures, i.e. quantum dots with green or yellow-green emissions, have been prepared. The relationship of the optical properties and the synthetic conditions has been further discussed. This strategy realizes the convenient preparation of ZnO QDs, indicating the potential prospects in the nanotechnology field for their low-cost synthesis. Meanwhile, the cellular toxicity study of ZnO nanoparticles toward cancer cells, including leukemia K562 and K562/A02 cells as well as HepG2 cells, indicates a selective cytotoxic effect of ZnO QDs against a broad range of human cancer cell lines.

Zhang, Yinzhu; Wang, Huangping; Jiang, Hui; Wang, Xuemei

2012-05-01

296

The synthesis and characterization of poly(?-glutamic acid)-coated magnetite nanoparticles and their effects on antibacterial activity and cytotoxicity.  

PubMed

Magnetite nanoparticles (MNPs) modified with sodium and calcium salts of poly(?-glutamic acid) (NaPGA and CaPGA) were synthesized by the coprecipitation method, followed by characterization and evaluation of their antibacterial and cytotoxic effects. Superparamagnetic MNPs are particularly attractive for magnetic driving as well as bacterial biofilm and cell targeting in in vivo applications. Characterization of synthesized MNPs by the Fourier transform infrared spectra and magnetization curves confirmed the PGA coating on MNPs. The mean diameter of NaPGA- and CaPGA-coated MNPs as determined by transmission electron microscopy was 11.8 and 14 nm, respectively, while the x-ray diffraction pattern revealed the as-synthesized MNPs to be pure magnetite. Based on agar dilution assay, both NaPGA- and CaPGA-coated MNPs showed a lower minimum inhibitory concentration in Salmonella enteritidis SE 01 than the commercial antibiotics linezolid and cefaclor, but the former was effective against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 10832, whereas the latter was effective against Escherichia coli O157:H7 TWC 01. An in vitro cytotoxicity study in human skin fibroblast cells as measured by MTT assay implied the as-synthesized MNPs to be nontoxic. This outcome demonstrated that both ?-PGA-modified MNPs are cytocompatible and possess antibacterial activity in vitro, and thereby should be useful in in vivo studies for biomedical applications. PMID:21233545

Inbaraj, B Stephen; Kao, T H; Tsai, T Y; Chiu, C P; Kumar, R; Chen, B H

2011-02-18

297

The synthesis and characterization of poly(?-glutamic acid)-coated magnetite nanoparticles and their effects on antibacterial activity and cytotoxicity  

NASA Astrophysics Data System (ADS)

Magnetite nanoparticles (MNPs) modified with sodium and calcium salts of poly(?-glutamic acid) (NaPGA and CaPGA) were synthesized by the coprecipitation method, followed by characterization and evaluation of their antibacterial and cytotoxic effects. Superparamagnetic MNPs are particularly attractive for magnetic driving as well as bacterial biofilm and cell targeting in in vivo applications. Characterization of synthesized MNPs by the Fourier transform infrared spectra and magnetization curves confirmed the PGA coating on MNPs. The mean diameter of NaPGA- and CaPGA-coated MNPs as determined by transmission electron microscopy was 11.8 and 14 nm, respectively, while the x-ray diffraction pattern revealed the as-synthesized MNPs to be pure magnetite. Based on agar dilution assay, both NaPGA- and CaPGA-coated MNPs showed a lower minimum inhibitory concentration in Salmonella enteritidis SE 01 than the commercial antibiotics linezolid and cefaclor, but the former was effective against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 10832, whereas the latter was effective against Escherichia coli O157:H7 TWC 01. An in vitro cytotoxicity study in human skin fibroblast cells as measured by MTT assay implied the as-synthesized MNPs to be nontoxic. This outcome demonstrated that both ?-PGA-modified MNPs are cytocompatible and possess antibacterial activity in vitro, and thereby should be useful in in vivo studies for biomedical applications.

Inbaraj, B. Stephen; Kao, T. H.; Tsai, T. Y.; Chiu, C. P.; Kumar, R.; Chen, B. H.

2011-02-01

298

Rapid assessment of antiviral activity and cytotoxicity of silver nanoparticles using a novel application of the tetrazolium-based colorimetric assay.  

PubMed

This study centers on the development of a new screening tool for simultaneously evaluating the antiviral and cytotoxic properties of antiviral agents against an HIV-1-based, pseudotyped virus particle engineered to encode antibiotic resistance. The traditional colony-forming-unit assay for quantifying this type of virus was impractical as a screening tool due to the cumbersome nature of the setup and high costs in labor and supplies. Therefore, a smaller-scale and higher-throughput means of scoring antiviral activity was successfully developed and used to evaluate a specific batch of 25-nm silver nanoparticles (AgNPs). The new assay employed a unique application of the traditional cell proliferation/cytotoxicity test that is based on the chemical 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, which produces a colorimetric readout. The AgNPs showed a half maximal inhibitory concentration against the virus of 11.2±0.6 ?g/ml (p<0.0001) with no significant toxicity against the cells. Because the virus was engineered to undergo only the first half of its replication cycle, the observed AgNP inhibition must have occurred at one of the early stages of infection. Overall, the new assay was very efficient and will be useful for testing different viral pseudotypes, screening different types of nanomaterials, and investigating other antiviral agents. PMID:22465243

Trefry, John C; Wooley, Dawn P

2012-07-01

299

Cytotoxic Activities of Silver Nanoparticles and Silver Ions in Parent and Tamoxifen-Resistant T47D Human Breast Cancer Cells and Their Combination Effects with Tamoxifen against Resistant Cells  

PubMed Central

Studies on biomedical applications of nanoparticles are growing with a rapid pace. In medicine, nanoparticles may be the solution for multi-drug-resistance which is still a major drawback in chemotherapy of cancer. In the present study, we investigated the potential cytotoxic effect of silver nanoparticles (Ag NPs) and silver ions (Ag+) in both parent and tamoxifen-resistant T47D cells in presence and absence of tamoxifen. Ag NPs were synthesized (< 28 nm) and MTT assay was carried out. The associated IC50 values were found to be: 6.31 µg/ml for Ag NPs/parent cells, 37.06 µg/ml for Ag NPs/tamoxifen-resistant cells, 33.06 µg/ml for Ag+/parent cells and 10.10 µg/ml for Ag+/resistant cells. As a separate experiment, the effect of subinhibitory concentrations of Ag NPs and Ag+ on the proliferation of tamoxifen-resistant cells was evaluated at non-toxic concentrations of tamoxifen. Our results suggested that in non-cytotoxic concentrations of silver nanomaterials and tamoxifen, the combinations of Ag+-tamoxifen and Ag NPs-tamoxifen are still cytotoxic. This finding may be of great potential benefit in chemotherapy of breast cancer; since much lower doses of tamoxifen may be needed to produce the same cytotoxic effect and side effects will be reduced. PMID:23408729

Ostad, Seyed Naser; Dehnad, Shahrzad; Nazari, Zeinab Esmail; Fini, Shohreh Tavajohi; Mokhtari, Narges; Shakibaie, Mojtaba; Shahverdi, Ahmad Reza

2010-01-01

300

N?acetyl?L?cysteine reduces arsenite?induced cytotoxicity through chelation in U937 monocytes and macrophages.  

PubMed

In the present study, in order to clarify the preventive mechanism of N?acetyl?L?cysteine (NAC) on arsenite?induced apoptosis in U937 cells, which lack functional p53, the cytotoxicity among U937 cells [monocytes and 12?O?tetradecanoylphorbol?13?acetate (TPA)?treated macrophages] receiving NAC treatment at different times post arsenite treatment was examined. TPA?treated macrophages were more resistant to arsenite?induced apoptosis than monocytes, which may be associated with the induction of Bcl?2 expression. Pretreatment with 20 mM NAC prior to arsenite exposure suppressed apoptosis up to 75% in the monocytes and 100% in the macrophages. However, 6?h NAC pretreatment and subsequent washing out of NAC from the culture medium prior to arsenite treatment did not inhibit the arsenite?induced apoptosis. Post?treatment by NAC up to 1 h following arsenite exposure almost completely inhibited the cytotoxic effects of arsenite in U937 monocytes and macrophages. The results of the current study indicate that the preventive mechanism of NAC on arsenite?induced apoptosis in U937 monocytes and macrophages mainly involves chelation of arsenite in culture medium. PMID:25310083

Ghani, Sidra; Khan, Noureen; Koriyama, Chihaya; Akiba, Suminori; Yamamoto, Megumi

2014-12-01

301

NANO EXPRESS Open Access H2-induced copper and silver nanoparticle  

E-print Network

NANO EXPRESS Open Access H2-induced copper and silver nanoparticle precipitation inside sol-gel silica optical fiber preforms Abdallah Chahadih, Hicham El Hamzaoui, Odile Cristini, Laurent Bigot, Rémy nanoparticles with diameters in the range of 3 to 6 nm and nano-rods were obtained. Keywords: copper

Paris-Sud XI, Université de

302

Chlorin e6 fused with a cobalt-bis(dicarbollide) nanoparticle provides efficient boron delivery and photoinduced cytotoxicity in cancer cells.  

PubMed

Further development of boron neutron capture therapy (BNCT) requires new neutronsensitizers with improved ability to deliver (10)B isotopes in cancer cells. Conjugation of boron nanoparticles with porphyrin derivatives is an attractive and recognized strategy to solve this task. We report on breakthroughs in the structural optimization of conjugates of chlorin e6 derivative with cobalt-bis(dicarbollide) nanoparticles resulting in the creation of dimethyl ester 13-carbomoylchlorin e6 [N-hexylamine-N'-ethoxyethoxy]-cobalt-bis(dicarbollide) (conjugate 1). Conjugate 1 is able to accumulate quickly and efficiently (distribution factor of 80) in cancer cells, thus delivering more than 10(9) boron atoms per cell when its extracellular concentration is more than 1 ?mol L(-1). Also 1 is an active photosensitizer and is phototoxic towards human lung adenocarcinoma A549 cells at 80 nmol L(-1) (50% cell death). Photoinduced cytotoxicity of 1 is associated with lipid peroxidation, lysosome rupture and protease activity enhancement. Conjugate 1 fluoresces in the red region (670 nm), which is useful to monitor its accumulation and distribution in vivo. It is not toxic to cells without activation by neutrons or photons. Structural features that improve the functional properties of 1 are discussed. The properties of 1 warrant its preclinical evaluation as a multifunctional agent for BNCT, photodynamic therapy and fluorescent tumor diagnosis. PMID:24258161

Efremenko, Anastasija V; Ignatova, Anastasija A; Grin, Mikhail A; Sivaev, Igor B; Mironov, Andrey F; Bregadze, Vladimir I; Feofanov, Alexey V

2014-01-01

303

Increasing the cytotoxicity of doxorubicin in breast cancer MCF-7 cells with multidrug resistance using a mesoporous silica nanoparticle drug delivery system  

PubMed Central

Resistance to cytotoxic chemotherapy is the main cause of therapeutic failure and death in women with breast cancer. Overexpression of various members of the superfamily of adenosine triphosphate binding cassette (ABC)-transporters has been shown to be associated with multidrug resistance (MDR) phenotype in breast cancer cells. MDR1 protein promotes the intracellular efflux of drugs. A novel approach to address cancer drug resistance is to take advantage of the ability of nanocarriers to sidestep drug resistance mechanisms by endosomal delivery of chemotherapeutic agents. Doxorubicin (DOX) is an anthracycline antibiotic commonly used in breast cancer chemotherapy and a substrate for ABC-mediated drug efflux. In the present study, we developed breast cancer MCF-7 cells with overexpression of MDR1 and designed mesoporous silica nanoparticles (MSNs) which were used as a drug delivery system. We tested the efficacy of DOX in the breast cancer cell line MCF-7/MDR1 and in a MCF-7/MDR1 xenograft nude mouse model using the MSNs drug delivery system. Our data show that drug resistance in the human breast cancer cell line MCF-7/MDR1 can be overcome by treatment with DOX encapsulated within mesoporous silica nanoparticles. PMID:24817930

Wang, Xin; Teng, Zhaogang; Wang, Haiyan; Wang, Chunyan; Liu, Ying; Tang, Yuxia; Wu, Jiang; Sun, Jin; Wang, Hai; Wang, Jiandong; Lu, Guangming

2014-01-01

304

Tumor necrosis factor?related apoptosis?inducing ligand induces cytotoxicity specific to osteosarcoma by microRNA response elements.  

PubMed

As the most common primary bone neoplasm, osteosarcoma is highly aggressive and represents a high risk to human health. Biological agents, including tumor necrosis factor?related apoptosis?inducing ligand (TRAIL), are considered promising therapeutic strategies for osteosarcoma. The current issue limiting the application of TRAIL gene therapy is that normal cells are also affected due to the lack of tumor selectivity. The present study aimed to employ the miRNA response elements (MREs) of microRNA (miR)?34 and miR?122, which are tumor suppressors, to enable the selective expression of TRAIL by adenoviral vectors in osteosarcoma cells. The results revealed that miR?34 and miR?122 were underexpressed in osteosarcoma tissues, compared with normal tissues. The MREs of miR?34 and miR?122 ensured that the luciferase gene was expressed selectively in osteosarcoma cells. Adenovirus (Ad)?TRAIL?34?122, which expressed TRAIL in an miR?34 and miR?122?regulated manner, selectively expressed TRAIL in the osteosarcoma cells assessed, which was detected using reverse transcription quantitative polymerase chain reaction, immunoblotting and ELISA. Apoptosis and cytotoxicity were also detected in the osteosarcoma cells, compared with the normal cells. Animal experiments further indicated that Ad?TRAIL?34?122 was able to reduce the growth of osteosarcoma xenografts without toxicity to the liver. In conclusion, the present study identified a novel miRNA?regulated biological cancer therapy against osteosarcoma, which is tumor selective and may be promising for future clinical treatment. PMID:25335093

Xiao, Fei; Chen, Juwu; Lian, Chuanju; Han, Pengchao; Zhang, Chaoyang

2015-01-01

305

Lead sulfide nanoparticles increase cell wall chitin content and induce apoptosis in Saccharomyces cerevisiae.  

PubMed

Although there have been numerous studies on bacterial toxicity, the cytotoxicity of nanoparticles toward fungi remains poorly understood. We investigated the toxicity of various sizes of lead sulfide particles against the important model fungus, Saccharomyces cerevisiae. The smallest particle exerted the highest toxicity, inhibiting cell growth and decreasing cell viability, likely reflecting reduced sedimentation and persistent cell wall attack. In response to cell wall stress, S. cerevisiae showed an increase in the cell wall chitin content and the overexpression of FKS2 and PRM5, two genes of the cell wall integrity signaling pathway. Cell wall stress increased the concentration of intracellular reactive oxygen species, leading to mitochondrial dysfunction and cell apoptosis. The contribution of dissolved lead ions to the overall toxicity was negligible. These findings provide the first demonstration of the physiological protective response of a fungus toward nanoparticles, thereby contributing useful information to the assessment of the environmental impact of metal nanoparticles. PMID:24704549

Sun, Meiqing; Yu, Qilin; Hu, Mengyuan; Hao, Zhenwei; Zhang, Chengdong; Li, Mingchun

2014-05-30

306

Pouterin, a novel potential cytotoxic lectin-like protein with apoptosis-inducing activity in tumorigenic mammalian cells.  

PubMed

In this study, the cytotoxicity of pouterin in tumorigenic and non-tumorigenic mammalian cell lines was investigated. We found that HeLa, Hep-2 and HT-29 tumor cells were highly sensitive to pouterin cytotoxicity in a dose-dependent manner, whereas non-tumorigenic Vero cells and human lymphocytes were relatively resistant to the protein. Among the tumor cell lines, HeLa cells showed the highest susceptibility to pouterin cytotoxicity, exhibiting a time-dependent increase in LDH leakage and an IC(50) value of 5mug/mL. Morphological alterations such as rounding, cell shrinkage and chromatin condensation, consistent with apoptotic cell death were observed. Apoptosis induction was demonstrated by DNA fragmentation as detected by terminal dUTP nick-end labeling (TUNEL). Furthermore, HeLa cells incubated with pouterin showed disruption of the actin cytoskeleton. Western blot analysis revealed that pouterin caused increased expression of p21, thus indicating cell cycle arrest. Subsequent studies provided evidence that apoptosis may be partially explained in the activation of the tumor necrosis factor receptor 1 (TNFR1) signaling. Interestingly, a time-dependent decrease of the expression of p65 nuclear factor kappa B (NFkappaB) subunit, concomitant with a downregulation of the inhibitor of apoptosis protein 1 (IAP1) was observed, suggesting that TNFR-mediated apoptosis is the predominant pathway induced by pouterin in HeLa cells. PMID:18468651

Boleti, Ana Paula de A; Ventura, Cláudio A; Justo, Giselle Z; Silva, Rodrigo A; de Sousa, Ana Carolina T; Ferreira, Carmen V; Yano, Tomomasa; Macedo, Maria Lígia R

2008-06-15

307

Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity.  

PubMed

A highly distressing side-effect of cancer chemotherapy is chemotherapy-induced alopecia (CIA). Scalp cooling remains the only treatment for CIA, yet there is no experimental evidence to support the cytoprotective capacity of cooling. We have established a series of in vitro models for the culture of human keratinocytes under conditions where they adopt a basal, highly-proliferative phenotype thus resembling the rapidly-dividing sub-population of native hair-matrix keratinocytes. Using a panel of chemotherapy drugs routinely used clinically (docetaxel, doxorubicin and the active metabolite of cyclophosphamide 4-OH-CP), we demonstrate that although these drugs are highly-cytotoxic, cooling can markedly reduce or completely inhibit drug cytotoxicity, in agreement with clinical observations. By contrast, we show that cytotoxicity caused by specific combinatorial drug treatments cannot be adequately attenuated by cooling, supporting data showing that such treatments do not always respond well to cooling clinically. Importantly, we provide evidence that the choice of temperature may be critical in determining the efficacy of cooling in rescuing cells from drug-mediated toxicity. Therefore, despite their reductive nature, these in vitro models have provided experimental evidence for the clinically-reported cytoprotective role of cooling and represent useful tools for future studies on the molecular mechanisms of cooling-mediated cytoprotection. PMID:25091624

Al-Tameemi, Wafaa; Dunnill, Christopher; Hussain, Omar; Komen, Manon M; van den Hurk, Corina J; Collett, Andrew; Georgopoulos, Nikolaos T

2014-12-01

308

Protective Cytotoxic T-Cell Responses Induced by Venezuelan Equine Encephalitis Virus Replicons Expressing Ebola Virus Proteins  

PubMed Central

Infection with Ebola virus causes a severe disease accompanied by high mortality rates, and there are no licensed vaccines or therapies available for human use. Filovirus vaccine research efforts still need to determine the roles of humoral and cell-mediated immune responses in protection from Ebola virus infection. Previous studies indicated that exposure to Ebola virus proteins expressed from packaged Venezuelan equine encephalitis virus replicons elicited protective immunity in mice and that antibody-mediated protection could only be demonstrated after vaccination against the glycoprotein. In this study, the murine CD8+ T-cell responses to six Ebola virus proteins were examined. CD8+ T cells specific for Ebola virus glycoprotein, nucleoprotein, and viral proteins (VP24, VP30, VP35, and VP40) were identified by intracellular cytokine assays using splenocytes from vaccinated mice. The cells were expanded by restimulation with peptides and demonstrated cytolytic activity. Adoptive transfer of the CD8+ cytotoxic T cells protected filovirus naïve mice from challenge with Ebola virus. These data support a role for CD8+ cytotoxic T cells as part of a protective mechanism induced by vaccination against six Ebola virus proteins and provide additional evidence that cytotoxic T-cell responses can contribute to protection from filovirus infections. PMID:16254354

Olinger, Gene G.; Bailey, Michael A.; Dye, John M.; Bakken, Russell; Kuehne, Ana; Kondig, John; Wilson, Julie; Hogan, Robert J.; Hart, Mary Kate

2005-01-01

309

Fuel mediated solution combustion synthesis of ZnO supported gold clusters and nanoparticles and their catalytic activity and in vitro cytotoxicity.  

PubMed

Nanocomposites of gold nanoparticles and semiconductor ZnO with wurtzite structure, made by solution combustion synthesis (SCS), as a function of the Zn/fuel ratio with polyethylene glycol (PEG) as fuel exhibit the presence of both nanoparticles and clusters. Atomic gold clusters present on the surface of ZnO nanorods which can be identified by XPS and SEM are easily monitored and characterized by positive ion MALDI experiments as mostly odd numbered clusters, Au3 to Au11 in decreasing amounts. Low concentrations of the fuel produce AuClO and nanoparticles (NPs), with no clusters. Au-ZnO nanocomposites at all [Au] exhibit single blue shifted plasmon absorption and corresponding photoluminescence (PL). Increasing particle size prefers surface plasmon resonance (SPR) scattering of metal that could lead to PL enhancement; however, available ZnO surface in the Au-ZnO composite becomes more important than the particle size of the composite with higher [Au]. The catalytic activity of these Au-ZnO nanocomposites tested on 4-nitrophenol clearly revealed the presence of an intermediate with both NPs and clusters playing different roles. An in vitro study of cytotoxicity on MCF-7 cell lines revealed that these gold nanostructures have turned out to be powerful nanoagents for destruction of cancer cells even with small amounts of gold particles/clusters. The nanorods of ZnO, known to be nontoxic to normal cells, play a lesser role in the anticancer activity of these Au-ZnO nanocomposites. PMID:25271812

Chanu, T Inakhunbi; Muthukumar, Thangavelu; Manoharan, Periakaruppan T

2014-11-21

310

Enhanced function of cytotoxic T lymphocytes induced by dendritic cells modified with truncated PSMA and 4-1BBL  

PubMed Central

Interactions between costimulatory molecules and their receptors are vital for Ag-presenting dendritic cells (DCs) to initiate T cells activation, expansion and their antitumor immune responses. Augmentation of costimulatory signal due to the interaction of DCs and T cells may amplify, sustain and drive diversity of cytotoxic T lymphocytes (CTLs) and consequently enhance the antitumor response. 4-1BBL/4-1BB is such a pair of costimulatory ligand and receptor, playing an important role in the co-stimulation of CTLs. Previously, we demonstrated that DCs transduced with recombinant adenovirus encoding truncated PSMA (tPSMA) and m4-1BBL could induce prostate cancer regression in mouse models. In the present study, we further explored the adjuvant role of 4-1BBL in modulating CTLs activation induced by tPSMA gene-pulsed DCs. The apoptosis and cytotoxicity against tPSMA expressing RM-1 cells of CTLs were determined. Results showed that tPSMA gene-pulsed DCs effectively induced T lymphocyte activation and cytotoxicity, which was enhanced by upregulated expression of 4-1BBL, displaying better cell viability, lower CTLs apoptosis, higher expression anti-apoptotic protein of Bcl-xL and phosphorylation of P38, enhanced NF-?B activation, as well as more IFN-? production. These results demonstrated that 4-1BBL may play a significant role in the co-stimulation pathway for Ag-presenting DCs-mediated CTLs activity, which might be a beneficial adjuvant factor for DCs-based cancer immunotherapy. PMID:23295983

Youlin, Kuang; Li, Zhang; Xin, Gou; Mingchao, Xiao; Xiuheng, Liu; Xiaodong, Weng

2013-01-01

311

Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells  

PubMed Central

Background Saikosaponin-a and -d, two naturally occurring compounds derived from Bupleurum radix, have been shown to exert anti-cancer activity in several cancer cell lines. However, the effect of combination of saikosaponins with chemotherapeutic drugs has never been addressed. Thus, we investigated whether these two saikosaponins have chemosensitization effect on cisplatin-induced cancer cell cytotoxicity. Methods Two cervical cancer cell lines, HeLa and Siha, an ovarian cancer cell line, SKOV3, and a non-small cell lung cancer cell line, A549, were treated with saikosaponins or cisplatin individually or in combination. Cell death was quantitatively detected by the release of lactate dehydrogenase (LDH) using a cytotoxicity detection kit. Cellular ROS was analyzed by flow cytometry. Apoptosis was evaluated by AO/EB staining, flow cytometry after Anexin V and PI staining, and Western blot for caspase activation. ROS scavengers and caspase inhibitor were used to determine the roles of ROS and apoptosis in the effects of saikosaponins on cisplatin-induced cell death. Results Both saikosaponin-a and -d sensitized cancer cells to cisplatin-induced cell death in a dose-dependent manner, which was accompanied with induction of reactive oxygen species (ROS) accumulation. The dead cells showed typical apoptotic morphologies. Both early apoptotic and late apoptotic cells detected by flow cytometry were increased in saikosaponins and cisplatin cotreated cells, accompanied by activation of the caspase pathway. The pan-caspase inhibitor z-VAD and ROS scanvengers butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC) dramatically suppressed the potentiated cytotoxicity achieved by combination of saikosaponin-a or -d and cisplatin. Conclusions These results suggest that saikosaponins sensitize cancer cells to cisplatin through ROS-mediated apoptosis, and the combination of saikosaponins with cisplatin could be an effective therapeutic strategy. PMID:21143894

2010-01-01

312

Down-regulation of XIAP by AEG35156 in paediatric tumour cells induces apoptosis and sensitises cells to cytotoxic agents.  

PubMed

Resistance to conventional chemotherapy is a major problem in several paediatric tumours. One explanation for this is that tumour cells are unable to engage apoptosis after cytotoxic drug-induced damage. Inhibitor of apoptosis proteins (IAPs) function by inhibiting both effector (9) and initiator (3 and 7) caspases. Repression of the widely expressed X-linked IAP (XIAP) by RNAi sensitises adult tumour cells to cytotoxics in vitro. Antisense oligonucleotide (ASO)-induced down-regulation of XIAP is effective at inducing cell death and delaying the growth of adult tumour cells as xenografts and these agents are currently in phase II clinical trials. The importance of XIAP in paediatric tumours has not been characterised but high expression correlates with poor survival in childhood AML. We have used the novel XIAP ASO (AEG35156) to evaluate the effects of down-regulation of XIAP in paediatric tumour cells. Here, we show that AEG35156 can down-regulate XIAP in a number of paediatric cell lines including models of osteosarcoma, rhabdomyosarcoma and Ewing's sarcoma. Cell death assays demonstrated a higher proportion of dead cells after XIAP down-regulation by ASO and these cells displayed increased levels of cleaved caspase-3 and cleaved PARP, showing cell death was due to apoptosis. In long-term clonogenic assays, XIAP ASO sensitised 791T osteosarcoma cells to doxorubicin, etoposide and vincristine. The work presented here suggests that AEG35156, as a monotherapy or in combination with cytotoxic agents, may be of benefit in the treatment of paediatric tumours. PMID:21286665

Holt, Sarah V; Brookes, Karen E; Dive, Caroline; Makin, Guy W J

2011-04-01

313

Pre-exposure to heat shock inhibits peroxynitrite-induced activation of poly(ADP) ribosyltransferase and protects against peroxynitrite cytotoxicity in J774 macrophages  

Microsoft Academic Search

The reaction of nitric oxide (NO) with superoxide yields the cytotoxic oxidant peroxynitrite, produced during inflammation and shock. A novel pathway of peroxynitrite cytotoxicity involves activation of the nuclear enzyme poly(ADP) ribosyltransferase, and concomitant ADP-ribosylation, NAD+ consumption and exhaustion of intracellular energy stores. In the present report we provide evidence that pre-exposure of J774 macrophages to heat shock reduces peroxynitrite-induced

Csaba Szabó; Hector R. Wong; Andrew L. Salzman

1996-01-01

314

Study of the Ability of Phenacetin, Acetaminophen, and Aspirin to Induce Cytotoxicity, Mutation, and Morphological Transformationin C3H\\/10TV2 Clone 8 Mouse Embryo Cells1  

Microsoft Academic Search

Use of the analgesic compounds acetylsalicyclic acid (aspirin), phen- acetin, and acetaminophen has been correlated with increased risk of renal cancer in humans. Hence, we studied these compounds for ability to induce cytotoxicity, mutation to ouabain resistance, and morphological transformation in cultured C3H\\/10T'\\/2 clone 8 (lOT'\\/i) mouse embryo cells. All three compounds were cytotoxic from 0.5-mg\\/ml to 2-mg\\/ml concentrations as

Steven R. Patierno; Norman L. Lehman; Brian E. Henderson; Joseph R. Landolph

315

HSP90 Inhibitors, Geldanamycin and Radicicol, Enhance Fisetin-Induced Cytotoxicity via Induction of Apoptosis in Human Colonic Cancer Cells.  

PubMed

We revealed the cytotoxic effect of the flavonoid, fisetin (FIS), on human COLO205 colon cancer cells in the presence and absence of the HSP90 inhibitors, geldanamycin (GA) and radicicol (RAD). Compared to FIS treatment alone of COLO205 cells, GA and RAD significantly enhanced FIS-induced cytotoxicity, increased expression of cleaved caspase-3 and the PAPR protein, and produced a greater density of DNA ladder formation. GA and RAD also reduced the MMPs with induction of caspase-9 protein cleavage in FIS-treated COLO205 cells. Increased caspase-3 and -9 activities were detected in COLO205 cells treated with FIS+GA or FIS+RAD, and the intensity of DNA ladder formation induced by FIS+GA was reduced by adding the caspase-3 inhibitor, DEVD-FMK. A decrease in Bcl-2 but not Bcl-XL or Bax protein by FIS+GA or FIS+RAD was identified in COLO205 cells by Western blotting. A reduction in p53 protein with increased ubiquitin-tagged proteins was observed in COLO205 cells treated with FIS+GA or FIS+RAD. Furthermore, GA and RAD reduced the stability of the p53 protein in COLO205 cells under FIS stimulation. The evidence supports HSP90 inhibitors possibly sensitizing human colon cancer cells to FIS-induced apoptosis, and treating colon cancer by combining HSP90 inhibitors with FIS deserves further in vivo study. PMID:23840275

Wu, Ming-Shun; Lien, Gi-Shih; Shen, Shing-Chuan; Yang, Liang-Yo; Chen, Yen-Chou

2013-01-01

316

Correlations between intercalator-induced DNA strand breaks and sister chromatid exchanges, mutations, and cytotoxicity in Chinese hamster cells.  

PubMed

Intercalator-induced DNA strand breaks in mammalian cells represent topoisomerase II:DNA complexes trapped by intercalators. These complexes are detected as protein-associated DNA single-strand breaks (SSB) and DNA double-strand breaks (DSB) by filter elution. Using Chinese hamster lung fibroblasts (V79 cells) that were treated for 30 min with various concentrations of 4'-(9-acridinylamino)methanesulfon-m-anisidide or 5-iminodaunorubicin, we measured DNA strand breaks (SSB and DSB), sister chromatid exchanges (SCE), mutations at the hypoxanthine:guanine phosphoribosyltransferase locus, and cell killing. Further, we correlated DNA strand breakage with the three other parameters. Both drugs induced SCE, mutations, and cell killing at concentrations which also produced reversible DNA strand breaks. While the quantity of DSB correlated with SCE, mutations, and cytotoxicity for both drugs, we found more SCE, mutations, and cytotoxicity per SSB in cells treated with 5-iminodaunorubicin than in those treated with 4'-(9-acridinylamino)methanesulfon-m-anisidide. These data show that the DSB (but not the SSB) induced by 4'-(9-acridinylamino)methanesulfon-m-anisidide and 5-iminodaunorubicin at DNA topoisomerase II binding sites correlated closely with SCE, mutations, and cell killing and could therefore be responsible for their production. PMID:2988762

Pommier, Y; Zwelling, L A; Kao-Shan, C S; Whang-Peng, J; Bradley, M O

1985-07-01

317

Electrically induced birefringence in nanoparticle dispersions for electrorheological applications  

NASA Astrophysics Data System (ADS)

Recently, the observation of an anomalously large electrorheological effect in the dispersion of nanosized particles of titania in octanoid acid has been reported. Such an enhanced effect was not observed in the similar dispersion of micrometric particles or in more conventional suspensions of silica in silicon oil. It was suggested that this effect could be promoted by the formation of a thin layer of solvent molecules on the surface of the titania particles. We propose the measurement of electrically induced optical birefringence as a suitable independent method for testing this working hypothesis. In this paper, we report the results from the investigations of the dilute dispersions of 32?nm TiO2 particles in two insulating fluids: silicone oil and octanoic acid. A comparison of the experimental birefringence data with the theoretical predictions suggests that TiO2 nanoparticles behave like permanent electric dipoles, although induced dipoles are expected in the case of the titania material. The source of such behaviour has been individuated at the particle/solvent interface and the different possibilities of the permanent dipole origin are discussed. The lower value of the dipole moment observed in octanoic acid dispersion is explained in terms of a specific particle/solvent interaction leading to the formation of a solvent coating around the particle. The results highlight that electro-optical properties are related to electrorheological performance and that both methods can be considered as supportive for testing electrically driven phenomena in complex fluids.

Pochylski, Mikolaj; Calandra, Pietro; Aliotta, Francesco; Ponterio, Rosina C.

2014-11-01

318

[Towards novel tuberculosis and leprosy vaccine development: the role of Th1-inducing peptide in cytotoxic T cell differentiation].  

PubMed

The effectiveness of a vaccine against tuberculosis and leprosy is mainly judged by its capability to induce memory CD8 cytotoxic T cells (CTL). It has been reported that 'help' from CD4+ T cells is required to induce memory CTL. However, how CD4+ T cells instruct or support memory CTL during priming phase has not been resolved in detail. Therefore, we examined the helper function of CD4+ T cells in CTL differentiation. Peptide-25 is the major T cell epitope of Ag85B of Mycobacterium tuberculosis. We found that this peptide induced the expression of T-bet and TATA box binding protein-associated factor that can induce the chromatin remodeling of ifn-gamma gene, and as a result induced Th1 differentiation even in the absence of IFN-gamma and IL-12. Next, we established an in vitro CTL differentiation system using Peptide-25, Peptide-25 specific CD4+ T cells, OVA specific CD8+ T cells and splenic DC. By using this system, we found that CD4+ T cells activated DC even in the absence of IFN-gamma and CD40 ligand association, and the activated DC induced the functional differentiation of CTL. To identify the regulatory factors for DC activation, we analyzed the gene expression profile of helper CD4 T cells and identified 27 genes. Taken together, these results suggest that the inducing factors for Th1 differentiation are not indispensable to induce the functional differentiation of CTL. PMID:24579458

Tamura, Toshiki; Shimohakamada, Yoko; Makino, Masahiko

2013-12-01

319

Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy.  

PubMed

Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50°C under relatively low nanoparticle concentrations (<1?mg/mL) and RF radiation intensities (1-5?W/cm(2)). For both types of nanoparticles the heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4?mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy. PMID:25391603

Tamarov, Konstantin P; Osminkina, Liubov A; Zinovyev, Sergey V; Maximova, Ksenia A; Kargina, Julia V; Gongalsky, Maxim B; Ryabchikov, Yury; Al-Kattan, Ahmed; Sviridov, Andrey P; Sentis, Marc; Ivanov, Andrey V; Nikiforov, Vladimir N; Kabashin, Andrei V; Timoshenko, Victor Yu

2014-01-01

320

In vitro and in vivo radiosensitization induced by hydroxyapatite nanoparticles  

PubMed Central

Background Previous study showed that hydroxyapatite nanoparticles (nano-HAPs) inhibited glioma growth in vitro and in vivo; and in a drug combination, they could reduce adverse reactions. We investigated the possible enhancement of radiosensitivity induced by nano-HAPs. Methods In vitro radiosensitization of nano-HAPs was measured using a clonogenic survival assay in human glioblastoma U251 and breast tumor brain metastatic tumor MDA-MB-231BR cells. DNA damage and repair were measured using ?H2AX foci, and mitotic catastrophe was determined by immunostaining. The effect of nano-HAPs on in vivo tumor radiosensitivity was investigated in a subcutaneous and an orthotopic model. Results Nano-HAPs enhanced each cell line's radiosensitivity when the exposure was 1 h before irradiation, and they had no significant effect on irradiation-induced apoptosis or on the activation of the G2 cell cycle checkpoint. The number of ?H2AX foci per cell was significantly large at 24 h after the combination modality of nano-HAPs + irradiation compared with single treatments. Mitotic catastrophe was also significantly increased at an interval of 72 h in tumor cells receiving the combined modality compared with the individual treatments. In a subcutaneous model, nano-HAPs caused a larger than additive increase in tumor growth delay. In an orthotopic model, nano-HAPs significantly reduced tumor growth and extended the prolongation of survival induced by irradiation. Conclusions These results show that nano-HAPs can enhance the radiosensitivity of tumor cells in vitro and in vivo through the inhibition of DNA repair, resulting in an increase in mitotic catastrophe. PMID:23519742

Chu, Sheng-Hua; Karri, Surya; Ma, Yan-Bin; Feng, Dong-Fu; Li, Zhi-Qiang

2013-01-01

321

Communication: Nanosize-induced restructuring of Sn nanoparticles  

NASA Astrophysics Data System (ADS)

Stabilities and structures of ?- and ?-Sn nanoparticles are studied using density functional theory. Results show that ?-Sn nanoparticles are more stable. For both phases of Sn, nanoparticles smaller than 1 nm (˜48 atoms) are amorphous and have a band gap between 0.4 and 0.7 eV. The formation of band gap is found to be due to amorphization. By increasing the size of Sn nanoparticles (1-2.4 nm), the degree of crystallization increases and the band gap decreases. In these cases, structures of the core of nanoparticles are bulk-like, but structures of surfaces on the faces undergo reconstruction. This study suggests a strong size dependence of electronic and atomic structures for Sn nanoparticle anodes in Li-ion batteries.

Sabet, Sareh; Kaghazchi, Payam

2014-05-01

322

Communication: Nanosize-induced restructuring of Sn nanoparticles.  

PubMed

Stabilities and structures of ?- and ?-Sn nanoparticles are studied using density functional theory. Results show that ?-Sn nanoparticles are more stable. For both phases of Sn, nanoparticles smaller than 1 nm (~48 atoms) are amorphous and have a band gap between 0.4 and 0.7 eV. The formation of band gap is found to be due to amorphization. By increasing the size of Sn nanoparticles (1-2.4 nm), the degree of crystallization increases and the band gap decreases. In these cases, structures of the core of nanoparticles are bulk-like, but structures of surfaces on the faces undergo reconstruction. This study suggests a strong size dependence of electronic and atomic structures for Sn nanoparticle anodes in Li-ion batteries. PMID:24852523

Sabet, Sareh; Kaghazchi, Payam

2014-05-21

323

Botulinum protease-cleaved SNARE fragments induce cytotoxicity in neuroblastoma cells.  

PubMed

Soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) are crucial for exocytosis, trafficking, and neurite outgrowth, where vesicular SNAREs are directed toward their partner target SNAREs: synaptosomal-associated protein of 25 kDa and syntaxin. SNARE proteins are normally membrane bound, but can be cleaved and released by botulinum neurotoxins. We found that botulinum proteases types C and D can easily be transduced into endocrine cells using DNA-transfection reagents. Following administration of the C and D proteases into normally refractory Neuro2A neuroblastoma cells, the SNARE proteins were cleaved with high efficiency within hours. Remarkably, botulinum protease exposures led to cytotoxicity evidenced by spectrophotometric assays and propidium iodide penetration into the nuclei. Direct delivery of SNARE fragments into the neuroblastoma cells reduced viability similar to botulinum proteases' application. We observed synergistic cytotoxic effects of the botulinum proteases, which may be explained by the release and interaction of soluble SNARE fragments. We show for the first time that previously observed cytotoxicity of botulinum neurotoxins/C in neurons could be achieved in cells of neuroendocrine origin with implications for medical uses of botulinum preparations. Ternary complex formation by synaptobrevin (green) and syntaxin/synaptosomal-associated protein of 25 kDa (red) is necessary for vesicle fusion, membrane trafficking, and cell homeostasis. Botulinum proteases cleave the three SNAREs proteins as indicated, resulting in a loss of cell viability. Lipofection reagents were used to deliver botulinum proteases or short SNARE peptides into neuroblastoma cells, revealing cytotoxic effects of SNARE fragments. PMID:24372287

Arsenault, Jason; Cuijpers, Sabine A G; Ferrari, Enrico; Niranjan, Dhevahi; Rust, Aleksander; Leese, Charlotte; O'Brien, John A; Binz, Thomas; Davletov, Bazbek

2014-06-01

324

Lipid molecules induce the cytotoxic aggregation of Cu\\/Zn superoxide dismutase with structurally disordered regions  

Microsoft Academic Search

Cu\\/Zn-superoxide dismutase (SOD1) is present in the cytosol, nucleus, peroxisomes and mitochondrial intermembrane space of human cells. More than 114 variants of human SOD1 have been linked to familial amyotrophic lateral sclerosis (ALS), which is also known as Lou Gehrig's disease. Although the ultimate mechanisms underlying SOD1-mediated cytotoxicity are largely unknown, SOD1 aggregates have been strongly implicated as a common

Inhee Choi; Young In Yang; Hyeon Don Song; Jeong Seon Lee; Taewook Kang; Jung-Joon Sung; Jongheop Yi

2011-01-01

325

Murine Splenic CD4+ T Cells, Induced by Innate Immune Cell Interactions and Secreted Factors, Develop Antileukemia Cytotoxicity.  

PubMed

Inciting the cellular arm of adaptive immunity has been the fundamental goal of cancer immunotherapy strategies, specifically focusing on inducing tumor antigen-specific responses by CD8(+) cytotoxic T lymphocytes (CTL). However, there is an emerging appreciation that the cytotoxic function of CD4(+) T cells can be effective in a clinical setting. Harnessing this potential will require an understanding of how such cells arise. In this study, we use an IL12-transduced variant of the 70Z/3 leukemia cell line in a B6D2F1 (BDF1) murine model system to reveal a novel cascade of cells and soluble factors that activate anticancer CD4(+) killer cells. We show that natural killer T cells play a pivotal role by activating dendritic cells in a contact-dependent manner; soluble products of this interaction, including MCP-1, propagate the activation signal, culminating in the development of CD4(+) CTLs that directly mediate an antileukemia response while also orchestrating a multipronged attack by other effector cells. A more complete picture of the conditions that induce such a robust response will allow us to capitalize on CD4(+) T-cell plasticity for maximum therapeutic effect. Cancer Immunol Res; 2(11); 1113-24. ©2014 AACR. PMID:25154710

Nelles, Megan E; Moreau, Joshua M; Furlonger, Caren L; Berger, Alexandra; Medin, Jeffrey A; Paige, Christopher J

2014-11-01

326

Cytotoxic and oxidative effects induced by man-made vitreous fibers (MMVFs) in a human mesothelial cell line.  

PubMed

The introduction of man-made vitreous fibers (MMVFs) as a substitute for asbestos in industrial and residential applications raises concerns about their potential health hazards. The aim of our study was to assess cytotoxic and oxidative effects induced on a human mesothelial cell line (MeT-5A) by exposure to glass wool (GW), rock wool (RW) and refractory ceramic fibers (RCF) in comparison with crocidolite asbestos (CR). MeT-5A cells were exposed for 24 h to 2, 5 and 10 microg/cm2 of MMVF and crocidolite fibers and analysed by scanning electron microscope (SEM) for cell surface alterations. Cells were exposed for 2 h to 1, 2, 5 and 10 microg/cm2 of the same fibers and analysed by enzyme Fpg-modified comet test for direct and oxidative DNA damage. SEM revealed loss of microvilli in cells exposed to RCF and numerous blebs in cells exposed to higher doses of RW. Comet test showed significant direct DNA damage in cells exposed to RCF even at the lowest dose. Comet test with Fpg, that permits the detection of oxided DNA bases, showed significant oxidative DNA damage in cells exposed to higher doses of RW. The presence of DNA damage and alterations of cell surface induced by low doses of RCF and the presence of oxidative DNA damage and blebs on cell surface in cells exposed to higher dose of RW suggest possible cytotoxic, oxidative and genotoxic effects for these MMVFs. PMID:15297035

Cavallo, Delia; Campopiano, Antonella; Cardinali, Giorgia; Casciardi, Stefano; De Simone, Paolo; Kovacs, Daniela; Perniconi, Barbara; Spagnoli, Giuseppe; Ursini, Cinzia L; Fanizza, Carla

2004-09-01

327

Cytotoxicity induced by ochratoxin A, zearalenone, and ?-zearalenol: effects of individual and combined treatment.  

PubMed

This study investigated the cytotoxicity of combined mycotoxins of ochratoxin A (OTA), zearalenone (ZEA), and/or ?-zearalenol (?-ZOL). The cytotoxicity of two mycotoxin combinations (two two-toxin combinations and one three-toxin combination) on human Hep G2 cells was evaluated using a tetrazolium salt (MTT) assay and isobologram analysis. Our results demonstrated significant cytotoxic effects of the two-toxin combination and the three-toxin combination on Hep G2 cells in a time- and concentration-dependent manner. The combination indexes (CI) were 2.73-7.67 for the OTA+ZEA combination and 1.23-17.82 for the OTA+?-ZOL combination after 24 h, 48 h, and 72 h of exposure at all inhibit concentration (IC) levels (IC10-IC90), indicating an antagonism. The CIs of the ZEA+?-ZOL combination were 1.29-2.55 after 24 h and 72 h of exposure (IC10-IC90), indicating an antagonism. The CIs of the ZEA+?-ZOL combination were 0.74-1.68 after 48 h of exposure, indicating synergism (IC80-IC90), additive effects (IC50-IC70), or antagonism (IC10-IC40). For the OTA+ZEA+?-ZOL combination, the CIs were 1.41-14.65 after 24 h, 48 h, and 72 h of exposure (IC10-IC90), indicating an antagonism. PMID:24952310

Wang, H W; Wang, J Q; Zheng, B Q; Li, S L; Zhang, Y D; Li, F D; Zheng, N

2014-09-01

328

Botulinum protease-cleaved SNARE fragments induce cytotoxicity in neuroblastoma cells  

PubMed Central

Soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) are crucial for exocytosis, trafficking, and neurite outgrowth, where vesicular SNAREs are directed toward their partner target SNAREs: synaptosomal-associated protein of 25 kDa and syntaxin. SNARE proteins are normally membrane bound, but can be cleaved and released by botulinum neurotoxins. We found that botulinum proteases types C and D can easily be transduced into endocrine cells using DNA-transfection reagents. Following administration of the C and D proteases into normally refractory Neuro2A neuroblastoma cells, the SNARE proteins were cleaved with high efficiency within hours. Remarkably, botulinum protease exposures led to cytotoxicity evidenced by spectrophotometric assays and propidium iodide penetration into the nuclei. Direct delivery of SNARE fragments into the neuroblastoma cells reduced viability similar to botulinum proteases' application. We observed synergistic cytotoxic effects of the botulinum proteases, which may be explained by the release and interaction of soluble SNARE fragments. We show for the first time that previously observed cytotoxicity of botulinum neurotoxins/C in neurons could be achieved in cells of neuroendocrine origin with implications for medical uses of botulinum preparations. PMID:24372287

Arsenault, Jason; Cuijpers, Sabine A G; Ferrari, Enrico; Niranjan, Dhevahi; Rust, Aleksander; Leese, Charlotte; O'Brien, John A; Binz, Thomas; Davletov, Bazbek

2014-01-01

329

Effect of biflavones of Ginkgo biloba against UVB-induced cytotoxicity in vitro.  

PubMed

The effect of Ginkgo biloba extract on Ultraviolet B (UVB) irradiated fibroblasts was examined by using a neutral red dye uptake assay and a lactic dehydrogenase (LDH) release assay. Crude extract along with individual components, including flavone-glycosides and biflavones, were applied to cultured normal human skin fibroblasts for 12 hours, and 0, 20, 40 and 80 mJ/cm2 of UVB were irradiated. Two synthetic flavonoids, quercetin and rutin, which have polyphenol structures close to the flavonoids in Ginkgo biloba extract, were used to compare any structure-related activity under the same conditions. At the concentrations (from 0.25 to 2 mg/ml) treated with biflavone components (isoginkgetin/ginkgetin, sciadopitysin) and quercetin, high neutral red dye uptake was detected with gradual increases in UVB irradiation. The time-course release of LDH was determined as the cytotoxicity index (%) during 24 hours following a high dose UVB irradiation (200 mJ/cm2), and the pattern of this cytotoxicity index was similar to that of the neutral red dye uptake results. Sciadopitysin, isoginkgetin/ginkgetin and quercetin treatments lowered cytotoxicity indices to 50.81, 67.81 and 62.19%, respectively, compared to 95.38% for the untreated control. The antioxidant potential of biflavones of Ginkgo biloba could be explained on the basis of structure-related activity; hydroxy- and methyl-substitutions on the basic structure of these flavonoids played a role, as other reports have suggested. PMID:11449670

Kim, S J

2001-04-01

330

Different cell responses induced by exposure to maghemite nanoparticles.  

PubMed

Recent advances in nanotechnology have permitted the development of a wide repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for biomedical applications. Despite this remarkable potential, many questions still arise concerning the biocompatible nature of NPs when in contact with biological systems. Herein, we have investigated how controlled changes in the physicochemical properties of iron oxide NPs at their surface (i.e., surface charge and hydrodynamic size) affect, first, their interaction with cell media components and, subsequently, cell responses to NP exposure. For that purpose, we have prepared iron oxide NPs with three different coatings (i.e., dimercaptosuccinic acid - DMSA, (3-aminopropyl)triethoxysilane - APS and dextran) and explored the response of two different cell types, murine L929 fibroblasts and human Saos-2 osteoblasts, to their exposure. Interestingly, different cell responses were found depending on the NP concentration, surface charge and cell type. In this sense, neutral NPs, as those coated with dextran, induced negligible cell damage, as their cellular internalization was significantly reduced. In contrast, surface-charged NPs (i.e., those coated with DMSA and APS) caused significant cellular changes in viability, morphology and cell cycle under certain culture conditions, as a result of a more active cellular internalization. These results also revealed a particular cellular ability to detect and remember the original physicochemical properties of the NPs, despite the formation of a protein corona when incubated in culture media. Overall, conclusions from these studies are of crucial interest for future biomedical applications of iron oxide NPs. PMID:23963338

Luengo, Yurena; Nardecchia, Stefania; Morales, María Puerto; Serrano, M Concepción

2013-12-01

331

Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation  

PubMed Central

Amorphous silica nanoparticles (SiNPs) are being used in biomedical, pharmaceutical, and many other industrial applications entailing human exposure. However, their potential vascular and systemic pathophysiologic effects are not fully understood. Here, we investigated the acute (24 hours) systemic toxicity of intraperitoneally administered 50 nm and 500 nm SiNPs in mice (0.5 mg/kg). Both sizes of SiNPs induced a platelet proaggregatory effect in pial venules and increased plasma concentration of plasminogen activator inhibitor-1. Elevated plasma levels of von Willebrand factor and fibrinogen and a decrease in the number of circulating platelets were only seen following the administration of 50 nm SiNPs. The direct addition of SiNPs to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced with 50 nm SiNPs. Both sizes of SiNPs increased lactate dehydrogenase activity and interleukin 1? concentration. However, tumor necrosis factor ? concentration was only increased after the administration of 50 nm SiNPs. Nevertheless, plasma markers of oxidative stress, including 8-isoprostane, thiobarbituric acid reactive substances, catalase, and glutathione S-transferase, were not affected by SiNPs. The in vitro exposure of human umbilical vein endothelial cells to SiNPs showed a reduced cellular viability, and more potency was seen with 50 nm SiNPs. Both sizes of SiNPs caused a decrease in endothelium-dependent relaxation of isolated small mesenteric arteries. We conclude that amorphous SiNPs cause systemic inflammation and coagulation events, and alter vascular reactivity. Overall, the effects observed with 50 nm SiNPs were more pronounced than those with 500 nm SiNPs. These findings provide new insight into the deleterious effect of amorphous SiNPs on vascular homeostasis. PMID:24936130

Nemmar, Abderrahim; Albarwani, Sulayma; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Attoub, Samir; Ali, Badreldin H

2014-01-01

332

Heat-Induced Precipitation and Light-Induced Dissolution of Metal (Ag & Au) Nanoparticles in Hybrid Film  

Microsoft Academic Search

Metal nanoparticle-doped materials have attracted much attention because of their enhanced third-order nonlinear optical susceptibility. In their application, (1) controllable precipitation and (2) stability against photo-irradiation are essential concerns. Silver or gold nanoparticle-doped films were made from hybrid sol containing metal ions with their stabilizer on silica glass substrates by the sol-gel dip-coating technique and their heat-induced precipitation and photo-stability

S. Shibata; K. Miyajima; Y. Kimura; T. Yano

2004-01-01

333

Role of Th1-stimulating cytokines in bacillus Calmette-Gu?rin (BCG)-induced macrophage cytotoxicity against mouse bladder cancer MBT-2 cells  

PubMed Central

Previously, we have demonstrated that macrophages exhibited cytotoxicity toward mouse bladder cancer MBT-2 cells upon bacille Calmette–Guérin (BCG) stimulation. In this study, we have investigated the role of Th1-stimulating cytokines in BCG-induced macrophage cytotoxicity. Thioglycollate-elicited peritoneal exudate cells (PECs) were used as a conventional source for macrophages and the induction of PEC effector functions (cytolytic activity and cytokine production) by BCG was evaluated in vitro. The BCG-activated PECs showed potent cytotoxicity and killed MBT-2 cells in a dose-dependent manner. Depletion of T cells, natural killer (NK) cells, or both, in PEC preparations exhibited a marginal or small reduction of MBT-2 cell killing, suggesting that macrophages played a primary role in PEC cytotoxicity. Transwell assays indicated that the maximal PEC cytotoxicity required both direct cell–cell contact and soluble factors such as interferon (IFN)-? and tumour necrosis factor (TNF)-?. Neutralizing endogenous cytokines interleukin (IL)-12, IL-18, IFN-? or TNF-? reduced PEC cytotoxicity by 38%, 22%, 15% and 94%, respectively. Supplementation of BCG with recombinant (r)IL-2, rIL-12 or rIL-18 increased PEC cytotoxicity by approximately twofold. Compared with control BCG for PEC stimulation, rBCGs expressing IL-2 or IL-18 showed enhanced MBT-2 cell killing by PECs. Increased cytokine production (IFN-?, TNF-? and IL-6) was also observed in rBCG-stimulated PEC cultures. Taken together, these results suggest that Th1-stimulating cytokines play an important role in BCG-induced macrophage cytotoxicity and that combination of BCG with selected Th1-stimulating cytokines, either supplemented or expressed by BCG, may enhance the effect of BCG in the treatment of bladder cancer patients. PMID:16968412

Luo, Y; Yamada, H; Evanoff, D P; Chen, X

2006-01-01

334

Coalescence-induced crystallisation wave in Pd nanoparticles  

NASA Astrophysics Data System (ADS)

Palladium nanoparticles offer an attractive alternative to bulk palladium for catalysis, hydrogen storage and gas sensing applications. Their performance depends strongly on surface structure; therefore, nanoparticle coalescence can play an important role, as it determines the resultant structure of the active sites where reactions (e.g. catalysis) actually take place, i.e. facets, edges, vertices or protrusions. With this in mind, we performed classical molecular dynamics (MD) simulations and magnetron-sputtering inert gas condensation depositions of palladium nanoparticles, supported by high-resolution transmission electron microscopy (HRTEM), to study the mechanisms that govern their coalescence. Surface energy minimisation drove the interactions initially, leading to the formation of an interface/neck, as expected. Intriguingly, at a later stage, atomic rearrangements triggered a crystallisation wave propagating through the amorphous nanoparticles, leading to mono- or polycrystalline fcc structures. In the case of crystalline nanoparticles, almost-epitaxial alignment occurred and the formation of twins and surface protrusions were observed.

Grammatikopoulos, Panagiotis; Cassidy, Cathal; Singh, Vidyadhar; Sowwan, Mukhles

2014-07-01

335

Coalescence-induced crystallisation wave in Pd nanoparticles.  

PubMed

Palladium nanoparticles offer an attractive alternative to bulk palladium for catalysis, hydrogen storage and gas sensing applications. Their performance depends strongly on surface structure; therefore, nanoparticle coalescence can play an important role, as it determines the resultant structure of the active sites where reactions (e.g. catalysis) actually take place, i.e. facets, edges, vertices or protrusions. With this in mind, we performed classical molecular dynamics (MD) simulations and magnetron-sputtering inert gas condensation depositions of palladium nanoparticles, supported by high-resolution transmission electron microscopy (HRTEM), to study the mechanisms that govern their coalescence. Surface energy minimisation drove the interactions initially, leading to the formation of an interface/neck, as expected. Intriguingly, at a later stage, atomic rearrangements triggered a crystallisation wave propagating through the amorphous nanoparticles, leading to mono- or polycrystalline fcc structures. In the case of crystalline nanoparticles, almost-epitaxial alignment occurred and the formation of twins and surface protrusions were observed. PMID:25047807

Grammatikopoulos, Panagiotis; Cassidy, Cathal; Singh, Vidyadhar; Sowwan, Mukhles

2014-01-01

336

Coalescence-induced crystallisation wave in Pd nanoparticles  

PubMed Central

Palladium nanoparticles offer an attractive alternative to bulk palladium for catalysis, hydrogen storage and gas sensing applications. Their performance depends strongly on surface structure; therefore, nanoparticle coalescence can play an important role, as it determines the resultant structure of the active sites where reactions (e.g. catalysis) actually take place, i.e. facets, edges, vertices or protrusions. With this in mind, we performed classical molecular dynamics (MD) simulations and magnetron-sputtering inert gas condensation depositions of palladium nanoparticles, supported by high-resolution transmission electron microscopy (HRTEM), to study the mechanisms that govern their coalescence. Surface energy minimisation drove the interactions initially, leading to the formation of an interface/neck, as expected. Intriguingly, at a later stage, atomic rearrangements triggered a crystallisation wave propagating through the amorphous nanoparticles, leading to mono- or polycrystalline fcc structures. In the case of crystalline nanoparticles, almost-epitaxial alignment occurred and the formation of twins and surface protrusions were observed. PMID:25047807

Grammatikopoulos, Panagiotis; Cassidy, Cathal; Singh, Vidyadhar; Sowwan, Mukhles

2014-01-01

337

The endoplasmic reticulum is a target organelle for trivalent dimethylarsinic acid (DMA{sup III})-induced cytotoxicity  

SciTech Connect

The purpose of present study was to characterize the endoplasmic reticulum stress and generation of ROS in rat liver RLC-16 cells by exposing to trivalent dimethylarsinous acid (DMA{sup III}) and compared with that of trivalent arsenite (iAs{sup III}) and monomethylarsonous acid (MMA{sup III}). Protein kinase-like endoplasmic reticulum kinase (PERK) phosphorylation was significantly induced in cells exposed to DMA{sup III}, while there was no change in phosphorylated PERK (P-PERK) detected in cells after exposure to iAs{sup III} or MMA{sup III}. The generation of reactive oxygen species (ROS) after DMA{sup III} exposure was found to take place specifically in the endoplasmic reticulum (ER), while previous reports showed that ROS was generated in mitochondria following exposure to MMA{sup III}. Meanwhile, cycloheximide (CHX) which is an inhibitor of protein biosynthesis strongly inhibited the DMA{sup III}-induced intracellular ROS generation in the ER and the phosphorylation of PERK, suggesting the induction of ER stress probably occurs through the inhibition of the protein folding process. Activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) mRNA were induced by all three arsenic species, however, evidence suggested that they might be induced by different pathways in the case of iAs{sup III} and MMA{sup III}. In addition, ER resident molecular chaperone glucose-regulated protein78 (GRP78) was not affected by trivalent arsenicals, while it was induced in positive control only at high concentration (Thapsigargin;Tg), suggesting the GRP78 is less sensitive to low levels of ER stress. In summary, our findings demonstrate that the endoplasmic reticulum is a target organelle for DMA{sup III}-induced cytotoxicity. Highlights: ?ER is a target organelle for trivalent DMA{sup III}-induced cytotoxicity. ?Generation of ROS in ER can be induced specially by trivalent DMA{sup III}. ?ER-stress and generation of ROS are caused by the increase in unfolded proteins.

Naranmandura, Hua, E-mail: narenman@zju.edu.cn [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China)] [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Xu, Shi [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China)] [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Koike, Shota [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan)] [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan); Pan, Li Qiang [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China)] [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Chen, Bin [Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)] [Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Wang, Yan Wei; Rehman, Kanwal; Wu, Bin [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China)] [Department of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Chen, Zhe [Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou (China)] [Zhejiang Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou (China); Suzuki, Noriyuki, E-mail: n-suzuki@p.chiba-u.ac.jp [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan)] [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan)

2012-05-01

338

A review on radiation-induced nucleation and growth of colloidal metallic nanoparticles  

PubMed Central

This review presents an introduction to the synthesis of metallic nanoparticles by radiation-induced method, especially gamma irradiation. This method offers some benefits over the conventional methods because it provides fully reduced and highly pure nanoparticles free from by-products or chemical reducing agents, and is capable of controlling the particle size and structure. The nucleation and growth mechanism of metallic nanoparticles are also discussed. The competition between nucleation and growth process in the formation of nanoparticles can determine the size of nanoparticles which is influenced by certain parameters such as the choice of solvents and stabilizer, the precursor to stabilizer ratio, pH during synthesis, and absorbed dose. PMID:24225302

2013-01-01

339

Thermal accommodation coefficients for laser-induced incandescence sizing of metal nanoparticles in monatomic gases  

NASA Astrophysics Data System (ADS)

The capabilities of time-resolved laser-induced incandescence (TiRe-LII), a combustion diagnostic used almost exclusively to measure soot primary particles, could potentially be extended to size aerosolized metal nanoparticles. In order to do this, however, it is necessary to characterize the thermal accommodation coefficient, ?, which specifies the heat conduction rate between the laser-energized nanoparticles and the surrounding gas. This paper extends a molecular dynamics (MD) methodology to calculate ? for Fe/He, Fe/Ar, Mo/He, and Mo/Ar systems. A comparative analysis of the results shows that ? is most strongly influenced by the potential well between the gas molecule and nanoparticle surface. Finally, the MD-derived value for ? is used to recover the nanoparticle size distribution for TiRe-LII measurements made on molybdenum nanoparticles in argon.

Daun, K. J.; Sipkens, T. A.; Titantah, J. T.; Karttunen, M.

2013-09-01

340

Surface modification of amorphous nanosilica particles suppresses nanosilica-induced cytotoxicity, ROS generation, and DNA damage in various mammalian cells.  

PubMed

Recently, nanomaterials have been utilized in various fields. In particular, amorphous nanosilica particles are increasingly being used in a range of applications, including cosmetics, food technology, and medical diagnostics. However, there is concern that the unique characteristics of nanomaterials might induce undesirable effects. The roles played by the physical characteristics of nanomaterials in cellular responses have not yet been elucidated precisely. Here, by using nanosilica particles (nSPs) with a diameter of 70nm whose surface was either unmodified (nSP70) or modified with amine (nSP70-N) or carboxyl groups (nSP70-C), we examined the relationship between the surface properties of nSPs and cellular responses such as cytotoxicity, reactive oxygen species (ROS) generation, and DNA damage. To compare the cytotoxicity of nSP70, nSP70-N, or nSP70-C, we examined in vitro cell viability after nSP treatment. Although the susceptibility of each cell line to the nSPs was different, nSP70-C and nSP70-N showed lower cytotoxicity than nSP70 in all cell lines. Furthermore, the generation of ROS and induction of DNA damage in nSP70-C- and nSP70-N-treated cells were lower than those in nSP70-treated cells. These results suggest that the surface properties of nSP70 play an important role in determining its safety, and surface modification of nSP70 with amine or carboxyl groups may be useful for the development of safer nSPs. We hope that our results will contribute to the development of safer nanomaterials. PMID:23044420

Yoshida, Tokuyuki; Yoshioka, Yasuo; Matsuyama, Keigo; Nakazato, Yasutaro; Tochigi, Saeko; Hirai, Toshiro; Kondoh, Sayuri; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-Ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

2012-11-01

341

Protective effect of kombucha tea against tertiary butyl hydroperoxide induced cytotoxicity and cell death in murine hepatocytes.  

PubMed

Kombucha (KT), a fermented black tea (BT), is known to have many beneficial properties. In the present study, antioxidant property of KT has been investigated against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity using murine hepatocytes. TBHP, a reactive oxygen species inducer, causes oxidative stress resulting in organ pathophysiology. Exposure to TBHP caused a reduction in cell viability, increased membrane leakage and disturbed the intra-cellular antioxidant machineries in hepatocytes. TBHP exposure disrupted mitochondrial membrane potential and induced apoptosis as evidenced by flow cytometric analyses. KT treatment, however, counteracted the changes in mitochondrial membrane potential and prevented apoptotic cell death of the hepatocytes. BT treatment also reverted TBHP induced hepatotoxicity, however KT was found to be more efficient. This may be due to the formation of antioxidant molecules like D-saccharic acid-1,4-lactone (DSL) during fermentation process and are absent in BT. Moreover, the radical scavenging activities of KT were found to be higher than BT. Results of the study showed that KT has the potential to ameliorate TBHP induced oxidative insult and cell death in murine hepatocytes more effectively than BT. PMID:21800502

Bhattacharya, Semantee; Manna, Prasenjit; Gachhui, Ratan; Sil, Parames C

2011-07-01

342

Aging Induced Ag Nanoparticle Rearrangement under Ambient Atmosphere and Consequences for Nanoparticle-Enhanced DNA Biosensing  

PubMed Central

Localized surface plasmons of metallic nanoparticles can strongly amplify the magnitude of the surrounding electric field. This in turn enhances fluorescence from nearby fluorophores. However, little is known regarding how time-dependent changes in nanoparticle structure due to exposure to the ambient environment affect their behavior in plasmonic devices. Here, we report the interesting finding that the aging of a nanostructured Ag substrate in ambient atmosphere markedly improves the fluorescence signal of a plasmonic-based DNA detection system. The effect can be observed with an exposure time as short as two days, and a nearly 17-fold signal enhancement can be achieved with 30 days of aging. Analysis of substrate surface topography by atomic force microscopy (AFM) reveals a substantial change in nanoparticle morphology as the substrates age despite being covalently attached to a solid dry substrate. Nanoparticle morphological changes also manifest in extinction spectra. This process can be further accelerated by light. Together, our findings address the important question of Ag nanoparticle stability over time and its potential ramifications for plasmon-enabled sensors. They also imply that nanoparticle aging may be used strategically to tune nanoparticle size and geometry and plasmon spectrum, which may be beneficial for studies on plasmonics as well as sensor optimization. PMID:20857925

Peng, Hsin-I; Krauss, Todd D.; Miller, Benjamin L.

2010-01-01

343

In vitro cytotoxicity tests of ZnO - Bi2O3- Mn2O3-based varistor fabricated from ZnO micro and nanoparticle powders on L929 mouse cells  

NASA Astrophysics Data System (ADS)

The present study investigated the cytotoxicity of ZnO - Bi2O3- Mn2O3-varistors. To this effect, ZnO - Bi2O3- Mn2O3 varistors fabricated from ZnO micro-and nanoparticle powders are prepared via conventional ceramic processing method. The effects of ZnO particle size on the properties of ZnO varistors are also investigated. The strong solid-state reaction during sintering may be attributed to the high surface area of the 20 nm ZnO nanoparticles that promote strong surface reaction. The intensity of XRD peaks reflected the high degree of crystallinity of the ZnO nanoparticles. However, the width of the peaks in case of ZnO nanoparticles has increased due to the quantum size effect. The cytotoxicity evaluation of ZnO varistor was conducted on mouse connective tissue fibroblast cells (L929) using Trypan Blue Exclusion Assay analysis. The results show that the four types of varistor samples lead to cellular mitochondrial dysfunction, morphological modifications and apoptosis at the various concentration range and the toxic effects are obviously displayed in high concentration samples. 20nm-VDR is the most toxic materials followed by 40nm-VDR, P8-VDR, and W4-VDR in a descending order.

Sendi, Rabab Khalid; Mahmud, Shahrom; Munshi, Ayman; Seeni, Azman

2014-10-01

344

A novel ?-sheet breaker, RS-0406, reverses amyloid ?-induced cytotoxicity and impairment of long-term potentiation in vitro  

PubMed Central

Fibril formation of amyloid ? peptide (A?) is considered to be responsible for the pathology of Alzheimer's disease (AD). The A? fibril is formed by a protein misfolding process in which intermolecular ?-sheet interactions become stabilized abnormally. Thus, to develop potential anti-AD drugs, we screened an in-house library to find compounds which have a profile as a ?-sheet breaker. We searched for a ?-sheet breaker profile in an in-house library of approximately 113,000 compounds. From among the screening hits, we focused on N,N?-bis(3-hydroxyphenyl)pyridazine-3,6-diamine (named RS-0406), which had been newly synthesized in our laboratory. This compound (10–100 ?g ml?1) was found to be capable of significantly inhibiting 25 ?M A?1–42 fibrillogenesis and, furthermore, disassembling preformed A?1–42 fibrils in vitro. We then investigated the effect of RS-0406 on 111 nM A?1–42-induced cytotoxicity in primary hippocampal neurons, and found that 0.3–3 ?g ml?1 RS-0406 ameliorates the cytotoxicity. Moreover, 3 ?g ml?1 RS-0406 reversed 1 ?M A?1–42-induced impairment of long-term potentiation in hippocampal slices. In this study, we have succeeded in identifying RS-0406 which has potential to inhibit A?1–42 fibrillogenesis, and to protect neurons against A?1–42-induced biological toxicity in vitro. These results suggest that RS-0406 or one of the derivatives could become a therapeutic agent for AD patients. PMID:12381681

Nakagami, Yasuhiro; Nishimura, Satoko; Murasugi, Takako; Kaneko, Isao; Meguro, Masaki; Marumoto, Shinji; Kogen, Hiroshi; Koyama, Kazuo; Oda, Tomiichiro

2002-01-01

345

Hepatoprotective constituents of the edible brown alga Ecklonia stolonifera on tacrine-induced cytotoxicity in Hep G2 cells.  

PubMed

In this study, ethanolic extracts from 18 seaweed variants were assessed for hepatoprotective activity against tacrine-induced cytotoxicity in Hep G2 cells. Only one of these, Ecklonia stolonifera Okamura (Laminariaceae), a member of the brown algae, exhibited promising hepatoprotective activity. Bioassay-guided fractionation of the active ethyl acetate (EtOAc) soluble fraction obtained from the ethanolic extract of E. stolonifera, resulted in the isolation of several phlorotannins [phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5)]. Compounds 2 and 4 were determined to protect Hep G2 cells against the cytotoxic effects of tacrine, with EC50 values of 62.0 and 79.2 microg/mL, respectively. Silybin, a well characterized hepatoprotective agent, was used as a positive control, and exhibited an EC50 value of 50.0 microg/mL. It has been suggested that the phlorotannins derived from marine brown algae might prove useful sources in the development of novel hepatoprotective agents. PMID:16392671

Kim, Youn Chul; An, Ren Bo; Yoon, Na Young; Nam, Taek Jeong; Choi, Jae Sue

2005-12-01

346

Changes in metal nanoparticle shape and size induced by swift heavy-ion irradiation  

NASA Astrophysics Data System (ADS)

Changes in the shape and size of Co, Pt and Au nanoparticles induced by swift heavy-ion irradiation (SHII) have been characterized using a combination of transmission electron microscopy, small-angle X-ray scattering and X-ray absorption near-edge structure. Elemental nanoparticles of diameters 2-15 nm were first formed in amorphous SiO 2 by ion implantation and thermal annealing and then irradiated at room temperature with 27-185 MeV Au ions as a function of fluence. Spherical nanoparticles below a minimum diameter (4-7 nm) remained spherical under SHII but progressively decreased in size as a result of dissolution into the SiO 2 matrix. Spherical nanoparticles above the minimum diameter threshold were transformed to elongated rods aligned with the ion beamdirection. The nanorod width saturated at an electronic energy deposition dependent value, progressively increasing from 4-6 to 7-10 nm (at 5-18 keV/nm, respectively) while the nanorod length exhibited a broad distribution consistent with that of the unirradiated spherical nanoparticles. The threshold diameter for spherical nanoparticle elongation was comparable to the saturation value of nanorod width. We correlate this saturation value with the diameter of the molten track induced in amorphous SiO 2 by SHII. In summary, changes in nanoparticle shape and size are governed to a large extent by the ion irradiation parameters.

Ridgway, M. C.; Kluth, P.; Giulian, R.; Sprouster, D. J.; Araujo, L. L.; Schnohr, C. S.; Llewellyn, D. J.; Byrne, A. P.; Foran, G. J.; Cookson, D. J.

2009-03-01

347

Cathepsin-B induced controlled release from Peptide-capped mesoporous silica nanoparticles.  

PubMed

New capped silica mesoporous nanoparticles for intracellular controlled cargo release within cathepsin?B expressing cells are described. Nanometric mesoporous MCM-41 supports loaded with safranin?O (S1-P) or doxorubicin (S2-P) containing a molecular gate based on a cathepsin?B target peptidic sequence were synthesized. Solids were designed to show "zero delivery" and to display cargo release in the presence of cathepsin?B enzyme, which selectively hydrolyzed in vitro the capping peptide sequence. Controlled delivery in HeLa, MEFs WT, and MEFs lacking cathepsin?B cell lines were also tested. Release of safranin?O and doxorubicin in these cells took place when cathepsin?B was active or present. Cells treated with S2-P showed a fall in cell viability due to nanoparticles internalization, cathepsin?B hydrolysis of the capping peptide, and cytotoxic agent delivery, proving the possible use of these nanodevices as new therapeutic tools for cancer treatment. PMID:25303093

de la Torre, Cristina; Mondragón, Laura; Coll, Carmen; Sancenón, Félix; Marcos, María D; Martínez-Máñez, Ramón; Amorós, Pedro; Pérez-Payá, Enrique; Orzáez, Mar

2014-11-17

348

Sunlight-induced reduction of ionic Ag and Au to metallic nanoparticles by dissolved organic matter.  

PubMed

Despite the possible occurrence of metal nanoparticles in the environment due to the discharge of engineered nanoparticles and the natural transformation of metal ions into metal nanoparticles, little is known about the transformation mechanism, fates, behaviors, and effects of these nanoparticles in the environment. Here, we show that dissolved organic matter (DOM) in environmental waters can mediate the reduction of ionic Ag and Au to their metallic nanoparticles under natural sunlight, suggesting that this process may be general for metals with high reduction potential. We demonstrated that the reduction was mediated by superoxide from photoirradiation of the phenol group in DOM, and the dissolved O(2) significantly enhanced the formation of Ag nanoparticles. These results imply that previous knowledge about O(2)-induced dissolution and its effect on persistence of Ag nanoparticles should be reconsidered in a sunlit DOM-rich aqueous environment. This study can also shed light on understanding possible natural sources of Ag and Au nanoparticles in the aquatic environment, which is possibly critical in the supergene enrichment of Ag and Au. PMID:22816495

Yin, Yongguang; Liu, Jingfu; Jiang, Guibin

2012-09-25

349

Electric-Field-Induced Alignment of Block Copolymer/Nanoparticle Blends  

SciTech Connect

External electric fi elds readily align birefringent block-copolymer mesophases. In this study the effect of gold nanoparticles on the electric-fi eld-induced alignment of a lamellae-forming polystyrene- block -poly(2-vinylpyridine) copolymer is assessed. Nanoparticles are homogeneously dispersed in the styrenic phase and promote the quantitative alignment of lamellar domains by substantially lowering the critical field strength above which alignment proceeds. The results suggest that the electric-fi eldassisted alignment of nanostructured block copolymer/nanoparticle composites may offer a simple way to greatly mitigate structural and orientational defects of such fi lms under benign experimental conditions.

Liedel, Clemens [RWTH Aachen University] [RWTH Aachen University; Schindler, Kerstin [RWTH Aachen University] [RWTH Aachen University; Pavan, Mariela J. [Hebrew University of Jerusalem] [Hebrew University of Jerusalem; Lewin, Christian [RWTH Aachen University] [RWTH Aachen University; Pester, Christian W [ORNL] [ORNL; Ruppel, Markus A [ORNL] [ORNL; Urban, Volker S [ORNL] [ORNL; Shenhar, Roy [Hebrew University of Jerusalem] [Hebrew University of Jerusalem; Boker, Alexander [RWTH Aachen University] [RWTH Aachen University

2013-01-01

350

Magnetic nanoparticle density mapping from the magnetically induced displacement data: a simulation study  

PubMed Central

Background Magnetic nanoparticles are gaining great roles in biomedical applications as targeted drug delivery agents or targeted imaging contrast agents. In the magnetic nanoparticle applications, quantification of the nanoparticle density deposited in a specified region is of great importance for evaluating the delivery of the drugs or the contrast agents to the targeted tissues. We introduce a method for estimating the nanoparticle density from the displacement of tissues caused by the external magnetic field. Methods We can exert magnetic force to the magnetic nanoparticles residing in a living subject by applying magnetic gradient field to them. The nanoparticles under the external magnetic field then exert force to the nearby tissues causing displacement of the tissues. The displacement field induced by the nanoparticles under the external magnetic field is governed by the Navier's equation. We use an approximation method to get the inverse solution of the Navier's equation which represents the magnetic nanoparticle density map when the magnetic nanoparticles are mechanically coupled with the surrounding tissues. To produce the external magnetic field inside a living subject, we propose a coil configuration, the Helmholtz and Maxwell coil pair, that is capable of generating uniform magnetic gradient field. We have estimated the coil currents that can induce measurable displacement in soft tissues through finite element method (FEM) analysis. Results From the displacement data obtained from FEM analysis of a soft-tissue-mimicking phantom, we have calculated nanoparticle density maps. We obtained the magnetic nanoparticle density maps by approximating the Navier's equation to the Laplacian of the displacement field. The calculated density maps match well to the original density maps, but with some halo artifacts around the high density area. To induce measurable displacement in the living tissues with the proposed coil configuration, we need to apply the coil currents as big as 104A. Conclusions We can obtain magnetic nanoparticle maps from the magnetically induced displacement data by approximating the Navier's equation under the assumption of uniform-gradient of the external magnetic field. However, developing a coil driving system with the capacity of up to 104A should be a great technical challenge. PMID:22394477

2012-01-01

351

Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes  

PubMed Central

Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg. PMID:25247425

Silva-Pereira, Liz Carmem; da Rocha, Carlos Alberto Machado; Cunha, Luiz Raimundo Campos da Silva e; da Costa, Edmar Tavares; Guimaraes, Ana Paula Araujo; Pontes, Thais Brilhante; Diniz, Domingos Luiz Wanderley Picanco; Leal, Mariana Ferreira; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodriguez

2014-01-01

352

Protective effect of prolactin against methylmercury-induced mutagenicity and cytotoxicity on human lymphocytes.  

PubMed

Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg. PMID:25247425

Silva-Pereira, Liz Carmem; da Rocha, Carlos Alberto Machado; Cunha, Luiz Raimundo Campos da Silva E; da Costa, Edmar Tavares; Guimarães, Ana Paula Araújo; Pontes, Thais Brilhante; Diniz, Domingos Luiz Wanderley Picanço; Leal, Mariana Ferreira; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodríguez

2014-09-01

353

Different cell responses induced by exposure to maghemite nanoparticles  

NASA Astrophysics Data System (ADS)

Recent advances in nanotechnology have permitted the development of a wide repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for biomedical applications. Despite this remarkable potential, many questions still arise concerning the biocompatible nature of NPs when in contact with biological systems. Herein, we have investigated how controlled changes in the physicochemical properties of iron oxide NPs at their surface (i.e., surface charge and hydrodynamic size) affect, first, their interaction with cell media components and, subsequently, cell responses to NP exposure. For that purpose, we have prepared iron oxide NPs with three different coatings (i.e., dimercaptosuccinic acid - DMSA, (3-aminopropyl)triethoxysilane - APS and dextran) and explored the response of two different cell types, murine L929 fibroblasts and human Saos-2 osteoblasts, to their exposure. Interestingly, different cell responses were found depending on the NP concentration, surface charge and cell type. In this sense, neutral NPs, as those coated with dextran, induced negligible cell damage, as their cellular internalization was significantly reduced. In contrast, surface-charged NPs (i.e., those coated with DMSA and APS) caused significant cellular changes in viability, morphology and cell cycle under certain culture conditions, as a result of a more active cellular internalization. These results also revealed a particular cellular ability to detect and remember the original physicochemical properties of the NPs, despite the formation of a protein corona when incubated in culture media. Overall, conclusions from these studies are of crucial interest for future biomedical applications of iron oxide NPs.Recent advances in nanotechnology have permitted the development of a wide repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for biomedical applications. Despite this remarkable potential, many questions still arise concerning the biocompatible nature of NPs when in contact with biological systems. Herein, we have investigated how controlled changes in the physicochemical properties of iron oxide NPs at their surface (i.e., surface charge and hydrodynamic size) affect, first, their interaction with cell media components and, subsequently, cell responses to NP exposure. For that purpose, we have prepared iron oxide NPs with three different coatings (i.e., dimercaptosuccinic acid - DMSA, (3-aminopropyl)triethoxysilane - APS and dextran) and explored the response of two different cell types, murine L929 fibroblasts and human Saos-2 osteoblasts, to their exposure. Interestingly, different cell responses were found depending on the NP concentration, surface charge and cell type. In this sense, neutral NPs, as those coated with dextran, induced negligible cell damage, as their cellular internalization was significantly reduced. In contrast, surface-charged NPs (i.e., those coated with DMSA and APS) caused significant cellular changes in viability, morphology and cell cycle under certain culture conditions, as a result of a more active cellular internalization. These results also revealed a particular cellular ability to detect and remember the original physicochemical properties of the NPs, despite the formation of a protein corona when incubated in c