Sample records for acids inhibit growth

  1. [Inhibition of growth of microscopic fungi with organic acids].

    PubMed

    Conková, E; Para, L; Kocisová, A

    1993-01-01

    Fungicidal effects of five selected organic acids (lactic, acetic, formic, oxalic, and propionic) in concentrations 3, 5, 10, 20 and 50 ml/l on nine selected species of moulds were tested. Lactic and oxalic acids did not prove the satisfactory fungicidal activity in any of the chosen concentrations. The antifungal effect of the other three acids, manifested by the growth inhibition of the tested moulds is shown in Tab. I and it can be expressed by sequence: propionic acid, formic acid, and acetic acid. These acids also had effects only in concentrations 20 ml/l and 50 ml/l. Propionic acid in concentration 20 ml/l inhibited the growth of five moulds (Penicillium glabrum, Aspergillus niger, Fusarium moniliforme, Aspergillus fumigatus, Cladosporium sphaerospermum). In testing of concentration 50 ml/l, the lower fungicidal ability was ascertained only in growth suppression of Aspergillus flavus. The fungicidal activity of formic acid was registered in concentration 20 ml/l in two cases and in concentration 50 ml/l in six cases. Acetic acid inhibited the growth in concentration 50 ml/l only in two cases. Tab. II shows the percentual evaluation of propionic acid and formic acid with regard to their inhibition abilities. The fungicidal efficiency of propionic acid resulting from the experiment is 88.9%. PMID:8122343

  2. Glycyrrhizic acid inhibits virus growth and inactivates virus particles.

    PubMed

    Pompei, R; Flore, O; Marccialis, M A; Pani, A; Loddo, B

    1979-10-25

    Screening investigations in antiviral action of plant extracts have revealed that a component of Glycyrrhiza glabra roots, found to be glycyrrhizie acid, is active against viruses. We report here that this drug inhibits growth and cytopathology of several unrelated DNA and RNA viruses, while not affecting cell activity and ability to replicate. In addition, glycyrrhizic acid inactivates herpes simplex virus particles irreversibly. PMID:233133

  3. Fatty acids and monoacylglycerols inhibit growth of Staphylococcus aureus.

    PubMed

    Kelsey, J A; Bayles, K W; Shafii, B; McGuire, M A

    2006-10-01

    Staphylococcus aureus causes a variety of human infections including toxic shock syndrome, osteomyelitis, and mastitis. Mastitis is a common disease in the dairy cow, and S. aureus has been found to be a major infectious organism causing mastitis. The objectives of this research were to determine which FA and esterified forms of FA were inhibitory to growth of S. aureus bacteria. FA as well as their mono-, di-, and triacylglycerol forms were tested for their ability to inhibit a human toxic shock syndrome clinical isolate (MN8) and two S. aureus clinical bovine mastitis isolates (305 and Novel). The seven most potent inhibitors across all strains tested by minimum inhibitory concentration analysis included lauric acid, glycerol monolaurate, capric acid, myristic acid, linoleic acid, cis-9, trans-11 conjugated linoleic acid, and trans-10, cis-12 conjugated linoleic acid. Some of these lipids were chosen for 48-h growth curve analysis with a bovine mastitis S. aureus isolate (Novel) at doses of 0, 20, 50, and 100 microg/mL except myristic acid, which was tested at 0, 50, 100, and 200 microg/mL. The saturated FA (lauric, capric, myristic) and glycerol monolaurate behaved similarly and reduced overall growth. In contrast, the polyunsaturated FA (linoleic and cis-9, trans-11 conjugated linoleic acid) delayed the time to initiation of exponential growth in a dose-dependent fashion. The results suggest that lipids may be important in the control of S. aureus during an infection. PMID:17180883

  4. Cinnamic Acid Increases Lignin Production and Inhibits Soybean Root Growth

    PubMed Central

    Salvador, Victor Hugo; Lima, Rogério Barbosa; dos Santos, Wanderley Dantas; Soares, Anderson Ricardo; Böhm, Paulo Alfredo Feitoza; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth. PMID:23922685

  5. Gymnemic acids inhibit hyphal growth and virulence in Candida albicans.

    PubMed

    Vediyappan, Govindsamy; Dumontet, Vincent; Pelissier, Franck; d'Enfert, Christophe

    2013-01-01

    Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine. PMID:24040201

  6. Gymnemic Acids Inhibit Hyphal Growth and Virulence in Candida albicans

    PubMed Central

    Vediyappan, Govindsamy; Dumontet, Vincent; Pelissier, Franck; d’Enfert, Christophe

    2013-01-01

    Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine. PMID:24040201

  7. Inhibition of tumoral cell respiration and growth by nordihydroguaiaretic acid.

    PubMed

    Pavani, M; Fones, E; Oksenberg, D; Garcia, M; Hernandez, C; Cordano, G; Muñoz, S; Mancilla, J; Guerrero, A; Ferreira, J

    1994-11-16

    The effects of nordihydroguaiaretic acid (NDGA), best known as an inhibitor of lipoxygenase activities, on the culture growth, oxygen consumption, ATP level, viability, and redox state of some electron carriers of intact TA3 and 786A ascites tumor cells have been studied. NDGA inhibited the respiration rate of these two tumor cell lines by preventing electron flow through the respiratory chain. Consequently, ATP levels, cell viability and culture growth rates were decreased. NDGA did not noticeably inhibit electron flow through both cytochrome oxidase and ubiquinone-cytochrome b-c1 complex. Also, the presence of NDGA changed to redox state of NAD(P)+ to a more reduced level, and the redox states of ubiquinone, cytochrome b and cytochromes c + c1 changed to a more oxidized level. These observations suggest that the electron transport in the tumor mitochondria was inhibited by NDGA at the NADH-dehydrogenase-ubiquinone level (energy-conserving site 1). As a consequence, mitochondrial ATP synthesis would be interrupted. This event could be related to the cytotoxic effect of NDGA. PMID:7986205

  8. Fish oil constituent docosahexa-enoic acid selectively inhibits growth of human papillomavirus immortalized keratinocytes

    Microsoft Academic Search

    DaZhi Chen; Karen Auborn

    The omega-3-fatty acids inhibit proliferation of breast cancer cells whereas omega-6-fatty acids stimulate growth. In this study, we examined effects of these fatty acids on human pre-cancerous cells. Cervical keratinocytes, immortalized with the oncogenic human papillomavirus (HPV) type 16, were treated with linoleic acid, an omega- 6-fatty acid, and the omega-3-fatty acids, eicosapentaenoic and docosahexaenoic acids. Using both cell counts

  9. Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis

    E-print Network

    Hammock, Bruce D.

    Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis from omega-6 ARA and epoxydocosapentaenoic acids (EDPs) from omega-3 docosahexaenoic acid (DHA) (14­16). DHA, which is the most abundant omega-3 fatty acid in most tissues (17, 18), can efficiently compete

  10. Polyunsaturated fatty acids inhibit melanoma cell growth in vitro.

    PubMed

    Zajdel, Alicja; Wilczok, Adam; Chodurek, Ewa; Gruchlik, Arkadiusz; Dzierzewicz, Zofia

    2013-01-01

    Human malignant melanoma is a highly aggressive and incurable cancer due to intrinsic resistance to apoptosis and reprogramming proliferation and survival pathways during progression. Numerous studies, including our own, linked arachidonic acid (AA, 20:4 n-6), eicosapentaenoic acid (EPA, 20:5 n-3), and docosahexaenoic acid (DHA, 22:6 n-3) supplementation to induction of apoptosis and decreased proliferation of various cancer cells. The cytotoxic effects result from lipid peroxidation and formation of reactive oxygen species (ROS), which modify proteins and nucleic acids. DNA damage by ROS causes mutations and genomic instability, leading to uncontrolled proliferation or cell death. In the present work, four human melanoma cell lines differing in origin, doubling time, metastatic potential, and melanin content (A375, A2058, G361, and C32) were exposed to AA, EPA or DHA added into culture media in the concentrations ranging from 0 (control) to 100 mM. After 24 h incubation cytotoxicity of the analyzed acids was determined with TOX-2 (In Vitro Toxicology Assay Kit XTT Based, TOX-2, Sigma) test. The oxidative protein modifications were measured using Aldehyde Site (DNA and Protein) Detection Kit (Cayman). All the acids tested showed marked inhibition of cell proliferation. The observed effects were statistically significant and depended on the concentration. Decrease of proliferation, associated by oxidative protein and DNA damage (measured as aldehyde sites in cells), was observed for EPA and DHA (50 mM and 100 mM) in A375, A2058, and G361 cells. In case of C32 cell line, which is amelanotic melanoma, EPA and DHA inhibited cell proliferation at 100 mM only. The effect of DHA was more pronounced. AA did not show its antiproliferative action in this cell line. The obtained results suggest that antiproliferative effects of the fatty acids in cultured human melanoma cells depend on the type of acid, its concentration and may be diverse when different melanoma cell lines are used. PMID:23614295

  11. The lactic acid bacteria metabolite phenyllactic acid inhibits both radial growth and sporulation of filamentous fungi

    PubMed Central

    2013-01-01

    Background Food spoilage caused by molds is a severe problem. In food and feed, e.g. dairy products, sourdough bread and silage, lactic acid bacteria are used as starter cultures. Besides lactic and acetic acid, some strains produce other low molecular weight compounds with antifungal activities. One of these metabolites is phenyllactic acid (PLA), well known for its antifungal effect. The inhibitory effect of PLA has only partially been investigated, and the objective of this study was to elucidate in detail the antifungal properties of PLA. Results We investigated the outgrowth of individual conidia from Aspergillus niger, Cladosporium cladosporioides and Penicillium roqueforti, and observed the morphologies of resulting colonies on solid media using different acid concentrations. We found that PLA inhibits molds similar to weak acid preservatives. Furthermore, it has an additional activity: at sub-inhibitory concentrations, fungal colonies displayed slower radial growth and inhibited sporulation. The L isoform of PLA is a more potent inhibitor than the D form. Increased expression of phiA was observed during PLA treatment. This gene was initially identified as being induced by Streptomyces-produced macrolide antibiotics, and is shown to be a structural protein in developed cells. This suggests that PhiA may act as a general stress protectant in fungi. Conclusion From a food protection perspective, the results of this study support the usage of lactic acid bacteria strains synthesizing PLA as starter cultures in food and feed. Such starter cultures could inhibit spore synthesis, which would be beneficial as many food borne fungi are spread by airborne spores. PMID:24229396

  12. The weak acid preservative sorbic acid inhibits conidial germination and mycelial growth of Aspergillus niger through intracellular acidification

    Microsoft Academic Search

    Andrew Plumridge; Stephan J. A. Hesse; Adrian J. Watson; Kenneth C. Lowe; Malcolm Stratford; David B. Archer

    2004-01-01

    The growth of the filamentous fungus Aspergillus niger, a common food spoilage organism, is inhibited by the weak acid preservative sorbic acid (trans-trans-2,4-hexadienoic acid). Conidia inoculated at 105\\/ml of medium showed a sorbic acid MIC of 4.5 mM at pH 4.0, whereas the MIC for the amount of mycelia at 24 h developed from the same spore inoculum was threefold

  13. Calcite crystal growth inhibition by humic substances with emphasis on hydrophobic acids from the Florida Everglades

    USGS Publications Warehouse

    Hoch, A.R.; Reddy, M.M.; Aiken, G.R.

    2000-01-01

    The crystallization of calcium carbonate minerals plays an integral role in the water chemistry of terrestrial ecosystems. Humic substances, which are ubiquitous in natural waters, have been shown to reduce or inhibit calcite crystal growth in experiments. The purpose of this study is to quantify and understand the kinetic effects of hydrophobic organic acids isolated from the Florida Everglades and a fulvic acid from Lake Fryxell, Antarctica, on the crystal growth of calcite (CaCO3). Highly reproducible calcite growth experiments were performed in a sealed reactor at constant pH, temperature, supersaturation (?? = 4.5), P(CO2) (10-3.5atm), and ionic strength (0.1 M) with various concentrations of organic acids. Higher plant-derived aquatic hydrophobic acids from the Everglades were more effective growth inhibitors than microbially derived fulvic acid from Lake Fryxell. Organic acid aromaticity correlated strongly with growth inhibition. Molecular weight and heteroatom content correlated well with growth inhibition, whereas carboxyl content and aliphatic nature did not. Copyright (C) 1999 Elsevier Science Ltd.

  14. Galacturonic Acid Inhibits the Growth of Saccharomyces cerevisiae on Galactose, Xylose, and Arabinose

    PubMed Central

    Huisjes, Eline H.; de Hulster, Erik; van Dam, Jan C.; Pronk, Jack T.

    2012-01-01

    The efficient fermentation of mixed substrates is essential for the microbial conversion of second-generation feedstocks, including pectin-rich waste streams such as citrus peel and sugar beet pulp. Galacturonic acid is a major constituent of hydrolysates of these pectin-rich materials. The yeast Saccharomyces cerevisiae, the main producer of bioethanol, cannot use this sugar acid. The impact of galacturonic acid on alcoholic fermentation by S. cerevisiae was investigated with anaerobic batch cultures grown on mixtures of glucose and galactose at various galacturonic acid concentrations and on a mixture of glucose, xylose, and arabinose. In cultures grown at pH 5.0, which is well above the pKa value of galacturonic acid (3.51), the addition of 10 g · liter?1 galacturonic acid did not affect galactose fermentation kinetics and growth. In cultures grown at pH 3.5, the addition of 10 g · liter?1 galacturonic acid did not significantly affect glucose consumption. However, at this lower pH, galacturonic acid completely inhibited growth on galactose and reduced galactose consumption rates by 87%. Additionally, it was shown that galacturonic acid strongly inhibits the fermentation of xylose and arabinose by the engineered pentose-fermenting S. cerevisiae strain IMS0010. The data indicate that inhibition occurs when nondissociated galacturonic acid is present extracellularly and corroborate the hypothesis that a combination of a decreased substrate uptake rate due to competitive inhibition on Gal2p, an increased energy requirement to maintain cellular homeostasis, and/or an accumulation of galacturonic acid 1-phosphate contributes to the inhibition. The role of galacturonic acid as an inhibitor of sugar fermentation should be considered in the design of yeast fermentation processes based on pectin-rich feedstocks. PMID:22582063

  15. Galacturonic acid inhibits the growth of Saccharomyces cerevisiae on galactose, xylose, and arabinose.

    PubMed

    Huisjes, Eline H; de Hulster, Erik; van Dam, Jan C; Pronk, Jack T; van Maris, Antonius J A

    2012-08-01

    The efficient fermentation of mixed substrates is essential for the microbial conversion of second-generation feedstocks, including pectin-rich waste streams such as citrus peel and sugar beet pulp. Galacturonic acid is a major constituent of hydrolysates of these pectin-rich materials. The yeast Saccharomyces cerevisiae, the main producer of bioethanol, cannot use this sugar acid. The impact of galacturonic acid on alcoholic fermentation by S. cerevisiae was investigated with anaerobic batch cultures grown on mixtures of glucose and galactose at various galacturonic acid concentrations and on a mixture of glucose, xylose, and arabinose. In cultures grown at pH 5.0, which is well above the pK(a) value of galacturonic acid (3.51), the addition of 10 g · liter(-1) galacturonic acid did not affect galactose fermentation kinetics and growth. In cultures grown at pH 3.5, the addition of 10 g · liter(-1) galacturonic acid did not significantly affect glucose consumption. However, at this lower pH, galacturonic acid completely inhibited growth on galactose and reduced galactose consumption rates by 87%. Additionally, it was shown that galacturonic acid strongly inhibits the fermentation of xylose and arabinose by the engineered pentose-fermenting S. cerevisiae strain IMS0010. The data indicate that inhibition occurs when nondissociated galacturonic acid is present extracellularly and corroborate the hypothesis that a combination of a decreased substrate uptake rate due to competitive inhibition on Gal2p, an increased energy requirement to maintain cellular homeostasis, and/or an accumulation of galacturonic acid 1-phosphate contributes to the inhibition. The role of galacturonic acid as an inhibitor of sugar fermentation should be considered in the design of yeast fermentation processes based on pectin-rich feedstocks. PMID:22582063

  16. Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells

    Microsoft Academic Search

    Patricia D. Schley; Humberto B. Jijon; Lindsay E. Robinson; Catherine J. Field

    2005-01-01

    Summary The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells in animal models and cell lines, but the mechanism by which this occurs is not well understood. In order to explore possible mechanisms for the modulation of breast cancer cell growth by omega-3 fatty acids, we examined the effects of

  17. Quantitative analysis of the modes of growth inhibition by weak organic acids in Saccharomyces cerevisiae.

    PubMed

    Ullah, Azmat; Orij, Rick; Brul, Stanley; Smits, Gertien J

    2012-12-01

    Weak organic acids are naturally occurring compounds that are commercially used as preservatives in the food and beverage industries. They extend the shelf life of food products by inhibiting microbial growth. There are a number of theories that explain the antifungal properties of these weak acids, but the exact mechanism is still unknown. We set out to quantitatively determine the contributions of various mechanisms of antifungal activity of these weak acids, as well as the mechanisms that yeast uses to counteract their effects. We analyzed the effects of four weak organic acids differing in lipophilicity (sorbic, benzoic, propionic, and acetic acids) on growth and intracellular pH (pH(i)) in Saccharomyces cerevisiae. Although lipophilicity of the acids correlated with the rate of acidification of the cytosol, our data confirmed that not initial acidification, but rather the cell's ability to restore pH(i), was a determinant for growth inhibition. This pH(i) recovery in turn depended on the nature of the organic anion. We identified long-term acidification as the major cause of growth inhibition under acetic acid stress. Restoration of pH(i), and consequently growth rate, in the presence of this weak acid required the full activity of the plasma membrane ATPase Pma1p. Surprisingly, the proposed anion export pump Pdr12p was shown to play an important role in the ability of yeast cells to restore the pH(i) upon lipophilic (sorbic and benzoic) acid stress, probably through a charge interaction of anion and proton transport. PMID:23001666

  18. Mechanisms of nordihydroguaiaretic acid-induced growth inhibition and apoptosis in human cancer cells

    PubMed Central

    Seufferlein, T; Seckl, M J; Schwarz, E; Beil, M; v Wichert, G; Baust, H; Lührs, H; Schmid, R M; Adler, G

    2002-01-01

    Lipoxygenase metabolites of arachidonic acid can act as growth promoting factors for various cancer cell lines. Here we demonstrate that the 5-lipoxygenase inhibitor nordihydroguaiaretic acid potently inhibits anchorage-independent growth of human pancreatic and cervical cancer cells in soft agar and delays growth of pancreatic and cervical tumours established in athymic mice. Furthermore, nordihydroguaiaretic acid induces apoptosis of these cancer cells in vitro and in vivo. Potential mechanisms mediating these effects of nordihydroguaiaretic acid were examined. Nordihydroguaiaretic acid had no inhibitory effect on growth and survival signals such as tyrosine phosphorylation of the epidermal growth factor receptor or basal and growth factor-stimulated activities of extracellular signal-regulated kinase 1/2, p70s6k and AKT but selectively inhibited expression of cyclin D1 in the cancer cells. In addition, treatment with nordihydroguaiaretic acid lead to a disruption of the filamentous actin cytoskeleton in human pancreatic and cervical cancer cells which was accompanied by the activation of Jun-NH2-terminal kinase and p38mapk. Similar effects were obtained by treatment of the cancer cells with cytochalasin D. These results suggest that nordihydroguaiaretic acid induces anoikis-like apoptosis as a result of disruption of the actin cytoskeleton in association with the activation of stress activated protein kinases. In conclusion, nordihydroguaiaretic acid could constitute a lead compound in the development of novel therapeutic agents for various types of cancer. British Journal of Cancer (2002) 86, 1188–1196. DOI: 10.1038/sj/bjc/6600186 www.bjcancer.com © 2002 Cancer Research UK PMID:11953870

  19. Fatty acids and monoacylglycerols inhibit growth of Staphylococcus aureus

    Microsoft Academic Search

    J. A. Kelsey; K. W. Bayles; B. Shafii; M. A. McGuire

    2006-01-01

    Staphylococcus aureus causes a variety of human infections including toxic shock syndrome, osteomyelitis, and mastitis. Mastitis is a common disease\\u000a in the dairy cow, andS. aureus has been found to be a major infectious organism causing mastitis. The objectives of this research were to determine which\\u000a FA and esterified forms of FA were inhibitory to growth ofS. aureus bacteria. FA

  20. Inhibition of Aspergillus growth and aflatoxin release by derivatives of benzoic acid.

    PubMed

    Chipley, J R; Uraih, N

    1980-08-01

    A study was conducted to determine the effects of o-nitrobenzoate, p-aminobenzoate, benzocaine (ethyl aminobenzoate), ethyl benzoate, methyl benzoate, salicylic acid (o-hydroxybenzoate), trans-cinnamic acid (beta-phenylacrylic acid), trans-cinnamaldehyde (3-phenylpropenal), ferulic acid (p-hydroxy-3-methoxycinnamic acid), aspirin (o-acetoxy benzoic acid), and anthranilic acid (o-aminobenzoic acid) upon growth and aflatoxin release in Aspergillus flavus NRRL 3145 and A. parasiticus NRRL 3240. A chemically defined medium was supplemented with various concentrations of these compounds and inoculated with spores, and the developing cultures were incubated for 4, 6, and 8 days at 27 degree C in a mechanical shaker. At the beginning of day 8 of incubation, aflatoxins were extracted from cell-free filtrates, separated by thin-layer chromatography, and quantitated by ultraviolet spectrophotometry. The structure of these aromatic compounds appeared to be critically related to their effects on mycelial growth and aflatoxin release. At concentrations of 2.5 and 5.0 mg per 25 ml of medium, methyl benzoate and ethyl benzoate were the most effective in reducing both mycelial growth and aflatoxin release by A. flavus and A. parasiticus. Inhibition of mycelial growth and aflatoxin release by various concentrations of the above-named aromatic compounds may indicate the possibility of their use as fungicides. PMID:6781406

  1. Growth inhibition and apoptosis induction of human melanoma cells by omega-hydroxy fatty acids.

    PubMed

    Abe, Akihisa; Sugiyama, Kanji

    2005-06-01

    We examined the anti-tumor activity and structure-activity requirements of omega-hydroxy fatty acids (omega-HFAs) on the human melanoma cell line G361. The omega-hydroxystearic acid (omega-HSA) had strong growth-inhibiting and cytotoxic activity. Although omega-hydroxypalmitic acid (omega-HPA) also had growth-inhibiting and cytotoxic activity, these effects were relatively low. The effects of both these acids were dose and time dependent. Further, DNA laddering, which is an index of apoptosis, was also observed in G361 cells on treatment with these compounds. On the other hand, the omega-HFAs tested in this study, omega-hydroxymyristic acid and omega-hydroxyeicosanoic acid, had no growth-inhibiting or cytotoxic activity. Treatment for 12 h with 100 microM of omega-HPA and omega-HSA resulted in the expression of caspase-3 activity, and then increased upon 24 h, suggesting that the cell death induced by omega-HPA and omega-HSA was apoptosis. Fatty acids and dicarboxylic acids, which are analogs of omega-HFAs, had no cytotoxicity. However, fatty alcohols and diols, which have a 16- to 18-carbon chain length had weak cytotoxicity. From these results, the most effective carbon chain length is 18. Furthermore, the hydroxyl group at one end of the carbon chain and the carboxyl group at the other end seem to be required for the cytotoxic effect. At least one end of the carbon chain must have a hydroxyl group. The carbon chain length of omega-HFAs appears to be closely related to the cytotoxicity. This study revealed the potent cytotoxic actions of omega-HFAs on the human melanoma cell line G361. PMID:15846120

  2. Growth inhibition of Clostridium thermocellum by carboxylic acids: A mechanism based on uncoupling by weak acids

    Microsoft Academic Search

    Alejandro A. Herrero; Reinaldo F. Gomez; Brad Snedecor; Cynthia J. Tolman; Mary F. Roberts

    1985-01-01

    The inhibition of Clostridium thermocellum strains by acetate and other organic acids (propionate, butyrate) can be explained by a model based on the chemiosmotic theory and uncoupler action. It is proposed that the charged permeant species in the process of anion exclusion is the dimer HA-2. Evidence for this mechanisms is provided by 31P-NMR studies of whole cells and cell

  3. Calcium Antagonists Inhibit Sustained Gibberellic Acid-Induced Growth of Avena (Oat) Stem Segments.

    PubMed Central

    Montague, M. J.

    1993-01-01

    The elongation response of Avena sativa (oat) stem segments to gibberellic acid (GA3) is of large magnitude, with high hormonal sensitivity and specificity, but without cell division activity. This system is therefore an excellent model for mechanistic studies on higher plant cell elongation and the action of gibberellin. At millimolar concentrations, the calcium antagonists verapamil, D-600, nicardipine, diltiazem, bepridil, 8-(N,N,-diethylamino)-octyl-3,4,5-trimethoxybenzoate HCl, and lanthanum substantially inhibited the growth of GA3-treated segments but had no effect on the elongation of nonhormone-treated segments. Although verapamil reduced the maximum growth rate and caused premature cessation of growth, even preincubation of the segments with the drug prior to treatment with GA3 failed to inhibit the earliest measured stimulation of growth by the hormone. Inhibition by verapamil was not reversed by increased concentrations of GA3 or calcium. Neither the calcium ionophore A23187 nor agonist BAY K 8644 had any effect on growth. Light microscopic examination of epidermal peels from antagonist-treated internodal tissue revealed no obvious differences from the control except that the cells were not as elongated. Although these results may support a role for calcium ion movement in maintaining the GA3-induced growth of Avena stem segments, they do not support the involvement of calcium ion movement in the hormone-mediated initiation of growth. PMID:12231695

  4. Exogenous Salicylic Acid Alleviates Growth Inhibition and Oxidative Stress Induced by Hypoxia Stress in Malus robusta Rehd

    Microsoft Academic Search

    Tuanhui Bai; Cuiying Li; Fengwang Ma; Huairui Shu; Mingyu Han

    2009-01-01

    Salicylic acid (SA) as a signal molecule mediates many biotic and environmental stress-induced physiologic responses in plants.\\u000a In this study we investigated the role of SA in regulating growth and oxidative stress in Malus robusta Rehd under both normoxic and hypoxic conditions. Hypoxia stress inhibited plant growth and dramatically reduced biomass.\\u000a Addition of SA significantly alleviated the plant growth inhibition.

  5. In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides

    PubMed Central

    Fluiter, Kees; ten Asbroek, Anneloor L. M. A.; de Wissel, Marit B.; Jakobs, Marja E.; Wissenbach, Margit; Olsson, Håkan; Olsen, Otto; Oerum, Henrik; Baas, Frank

    2003-01-01

    Locked nucleic acids (LNA) are novel high-affinity DNA analogs that can be used as genotype-specific drugs. The LNA oligonucleotides (LNA PO ODNs) are very stable in vitro and in vivo without the need for a phosphorothiolated backbone. In this study we tested the biological fate and the efficacy in tumor growth inhibition of antisense oligonucleotides directed against the gene of the large subunit of RNA polymerase II (POLR2A) that are completely synthesized as LNA containing diester backbones. These full LNA oligonucleotides strongly reduce POLR2A protein levels. Full LNA PO ODNs appeared to be very stable compounds when injected into the circulation of mice. Full LNA PO ODNs were continuously administered for 14 days to tumor-bearing nude mice. Tumor growth was inhibited sequence specifically at dosages from 1 mg/kg/day. LNA PO ODNs appeared to be non-toxic at dosages <5 mg/kg/day. Biodistribution studies showed the kidneys to have the highest uptake of LNA PO ODNs and urinary secretion as the major route of clearance. This report shows that LNA PO ODNs are potent genotype-specific drugs that can inhibit tumor growth in vivo. PMID:12560491

  6. Inhibition of Gallic Acid on the Growth and Biofilm Formation of Escherichia coli and Streptococcus mutans.

    PubMed

    Shao, Dongyan; Li, Jing; Li, Ji; Tang, Ruihua; Liu, Liu; Shi, Junling; Huang, Qingsheng; Yang, Hui

    2015-06-01

    New strategies for biofilm inhibition are becoming highly necessary because of the concerns to synthetic additives. As gallic acid (GA) is a hydrolysated natural product of tannin in Chinese gall, this research studied the effects of GA on the growth and biofilm formation of bacteria (Escherichia coli [Gram-negative] and Streptococcus mutans [Gram-positive]) under different conditions, such as nutrient levels, temperatures (25 and 37 °C) and incubation times (24 and 48 h). The minimum antimicrobial concentration of GA against the two pathogenic organisms was determined as 8 mg/mL. GA significantly affected the growth curves of both test strains at 25 and 37 °C. The nutrient level, temperature, and treatment time influenced the inhibition activity of GA on both growth and biofim formation of tested pathogens. The inhibition effect of GA on biofilm could be due to other factors in addition to the antibacterial effect. Overall, GA was most effective against cultures incubated at 37 °C for 24 h and at 25 °C for 48 h in various concentrations of nutrients and in vegetable wash waters, which indicated the potential of GA as emergent sources of biofilm control products. PMID:25974286

  7. GROWTH INHIBITION OF CLAVIBACTER MICHIGANENSIS subsp. MICHIGANENSIS AND PSEUDOMONAS SYRINGAE pv. TOMATO BY OLIVE MILL WASTEWATERS AND CITRIC ACID

    Microsoft Academic Search

    Z. Özdemir

    2009-01-01

    SUMMARY Effects of citric acid and olive mill wastewaters on the growth of seed-borne bacterial pathogens of tomato, Clavibacter michiganensis subsp. michiganensis and Pseudomonas syringae pv. tomato were investigated. Bacteria were exposed to citric acid (0.1 mol l -1 ) and 10 fold-diluted filter-sterilized olive mill wastewaters and their growth was determined by the plate count method. Citric acid inhibited

  8. Betulinic Acid Inhibits Prostate Cancer Growth through Inhibition of Specificity Protein Transcription Factors

    Microsoft Academic Search

    Sudhakar Chintharlapalli; Sabitha Papineni; Shashi K. Ramaiah

    2007-01-01

    Betulinic acid is a pentacyclic triterpene natural product initially identified as a melanoma-specific cytotoxic agent that exhibits low toxicity in animal models. Subsequent studies show that betulinic acid induces apoptosis and antiangiogenic responses in tumors derived from multiple tissues; however, the underlying mechanism of action is unknown. Using LNCaP prostate cancer cells as a model, we now show that betulinic

  9. Capric Acid Secreted by S. boulardii Inhibits C. albicans Filamentous Growth, Adhesion and Biofilm Formation

    PubMed Central

    Murzyn, Anna; Krasowska, Anna; Stefanowicz, Piotr; Dziadkowiec, Dorota; ?ukaszewicz, Marcin

    2010-01-01

    Candidiasis are life-threatening systemic fungal diseases, especially of gastro intestinal track, skin and mucous membranes lining various body cavities like the nostrils, the mouth, the lips, the eyelids, the ears or the genital area. Due to increasing resistance of candidiasis to existing drugs, it is very important to look for new strategies helping the treatment of such fungal diseases. One promising strategy is the use of the probiotic microorganisms, which when administered in adequate amounts confer a health benefit. Such a probiotic microorganism is yeast Saccharomyces boulardii, a close relative of baker yeast. Saccharomyces boulardii cells and their extract affect the virulence factors of the important human fungal pathogen C. albicans, its hyphae formation, adhesion and biofilm development. Extract prepared from S. boulardii culture filtrate was fractionated and GC-MS analysis showed that the active fraction contained, apart from 2-phenylethanol, caproic, caprylic and capric acid whose presence was confirmed by ESI-MS analysis. Biological activity was tested on C. albicans using extract and pure identified compounds. Our study demonstrated that this probiotic yeast secretes into the medium active compounds reducing candidal virulence factors. The chief compound inhibiting filamentous C. albicans growth comparably to S. boulardii extract was capric acid, which is thus responsible for inhibition of hyphae formation. It also reduced candidal adhesion and biofilm formation, though three times less than the extract, which thus contains other factors suppressing C. albicans adherence. The expression profile of selected genes associated with C. albicans virulence by real-time PCR showed a reduced expression of HWP1, INO1 and CSH1 genes in C. albicans cells treated with capric acid and S. boulardii extract. Hence capric acid secreted by S. boulardii is responsible for inhibition of C. albicans filamentation and partially also adhesion and biofilm formation. PMID:20706577

  10. Calcite growth-rate inhibition by fulvic acids isolated from Big Soda Lake, Nevada, USA, The Suwannee River, Georgia, USA and by polycarboxylic acids

    USGS Publications Warehouse

    Reddy, Michael M.; Leenheer, Jerry

    2011-01-01

    Calcite crystallization rates are characterized using a constant solution composition at 25°C, pH=8.5, and calcite supersaturation (?) of 4.5 in the absence and presence of fulvic acids isolated from Big Soda Lake, Nevada (BSLFA), and a fulvic acid from the Suwannee River, Georgia (SRFA). Rates are also measured in the presence and absence of low-molar mass, aliphatic-alicyclic polycarboxylic acids (PCA). BSLFA inhibits calcite crystal-growth rates with increasing BSLFA concentration, suggesting that BSLFA adsorbs at growth sites on the calcite crystal surface. Calcite growth morphology in the presence of BSLFA differed from growth in its absence, supporting an adsorption mechanism of calcite-growth inhibition by BSLFA. Calcite growth-rate inhibition by BSLFA is consistent with a model indicating that polycarboxylic acid molecules present in BSLFA adsorb at growth sites on the calcite crystal surface. In contrast to published results for an unfractionated SRFA, there is dramatic calcite growth inhibition (at a concentration of 1 mg/L) by a SRFA fraction eluted by pH 5 solution from XAD-8 resin, indicating that calcite growth-rate inhibition is related to specific SRFA component fractions. A cyclic PCA, 1, 2, 3, 4, 5, 6-cyclohexane hexacarboxylic acid (CHXHCA) is a strong calcite growth-rate inhibitor at concentrations less than 0.1 mg/L. Two other cyclic PCAs, 1, 1 cyclopentanedicarboxylic acid (CPDCA) and 1, 1 cyclobutanedicarboxylic acid (CBDCA) with the carboxylic acid groups attached to the same ring carbon atom, have no effect on calcite growth rates up to concentrations of 10 mg/L. Organic matter ad-sorbed from the air onto the seed crystals has no effect on the measured calcite crystal-growth rates.

  11. Inhibition of eryptosis and intraerythrocytic growth of Plasmodium falciparum by flufenamic acid.

    PubMed

    Kasinathan, Ravi S; Föller, Michael; Koka, Saisudha; Huber, Stephan M; Lang, Florian

    2007-01-01

    Non-selective (NSC) cation channels participate in the Ca(2+) leak of human erythrocytes. Sustained activity of these channels triggers suicidal erythrocyte death (eryptosis), which is characterized by Ca(2+)-stimulated cell shrinkage and phosphatidylserine (PS) exposure. PS-exposing erythrocytes are rapidly cleared from circulating blood. PGE(2) activates the NSC channels, and erythrocyte PGE(2) formation is stimulated by a decrease in intra- or extracellular Cl(-) concentration. In addition, the intraerythrocytic malaria parasite Plasmodium falciparum activates the NSC channels, most probably to accomplish Na(+) and Ca(2+) entry into the erythrocyte cytosol required for parasite development. By Ca(2+) uptake the parasite maintains a low Ca(2+) concentration in the erythrocyte cytosol and thus delays the suicidal death of the host erythrocyte. Flufenamic acid has previously been shown to inhibit NSC channels. The present study thus explored the effect of flufenamic acid on erythrocyte Ca(2+) entry, on suicidal erythrocyte death and on intraerythrocytic growth of P. falciparum. Within 48 h, replacement of extracellular Cl(-) with gluconate or application of PGE(2) (50 microM) increased Fluo3 fluorescence reflecting cytosolic Ca(2+) activity, decreased forward scatter reflecting cell volume and increased annexin V binding reflecting PS exposure in FACS analysis. All those effects were significantly blunted in the presence of flufenamic acid (10 microM). Flufenamic acid (25 microM) further significantly delayed the intraerythrocytic growth of P. falciparum and the PS exposure of the infected erythrocytes. The present observations disclose a novel effect of flufenamic acid, which may allow the pharmacological manipulation of erythrocyte survival and the course of malaria. PMID:17180616

  12. Inhibited growth of Pseudomonas aeruginosa by dextran- and polyacrylic acid-coated ceria nanoparticles

    PubMed Central

    Wang, Qi; Perez, J Manuel; Webster, Thomas J

    2013-01-01

    Ceria (CeO2) nanoparticles have been widely studied for numerous applications, but only a few recent studies have investigated their potential applications in medicine. Moreover, there have been almost no studies focusing on their possible antibacterial properties, despite the fact that such nanoparticles may reduce reactive oxygen species. In this study, we coated CeO2 nanoparticles with dextran or polyacrylic acid (PAA) because of their enhanced biocompatibility properties, minimized toxicity, and reduced clearance by the immune system. For the first time, the coated CeO2 nanoparticles were tested in bacterial assays involving Pseudomonas aeruginosa, one of the most significant bacteria responsible for infecting numerous medical devices. The results showed that CeO2 nanoparticles with either coating significantly inhibited the growth of Pseudomonas aeruginosa, by up to 55.14%, after 24 hours compared with controls (no particles). The inhibition of bacterial growth was concentration dependent. In summary, this study revealed, for the first time, that the characterized dextran- and PAA-coated CeO2 nanoparticles could be potential novel materials for numerous antibacterial applications. PMID:24039421

  13. Fatty acids inhibit growth-factor-induced diacylglycerol kinase alpha activation in vascular smooth-muscle cells.

    PubMed

    Du, X; Jiang, Y; Qian, W; Lu, X; Walsh, J P

    2001-07-01

    We have previously shown that unsaturated fatty acids amplify platelet-derived-growth-factor (PDGF)-induced protein kinase C (PKC) activation in vascular smooth-muscle cells (VSMCs). Diacylglycerol-induced PKC activation is normally terminated by diacylglycerol kinases (DGKs). We thus hypothesized that fatty acids act by inhibiting a DGK. Fractionation of VSMC extracts demonstrated that the DGK alpha isoform was the major DGK activity present. PDGF markedly increased the DGK activity of cultured cells. An inhibitor selective for the DGK alpha isoform, R59949 [3-[2-[4-(bis-(4-fluorophenyl)methylene]piperidin-1-yl)ethyl]-2,3-dihydro-2-thioxo-4(1H)-quinazolinone], abolished the growth-factor-induced increase in DGK activity, but had little effect on basal activity. PDGF thus selectively activates DGKalpha. Epidermal growth factor and alpha-thrombin stimulated total DGK activity similarly to PDGF. Activation by epidermal growth factor was sensitive to R59949, again suggesting involvement of DGKalpha. However, the alpha-thrombin-induced activity was unaffected by this agent. Unsaturated fatty acids inhibited growth-factor-induced DGKalpha activation, but had no effect on basal activity. Fatty acids also amplified the PDGF-induced increase in cell diacylglycerol content. These results indicate that inhibition of DGKalpha contributes to fatty-acid-induced amplification of PKC activation. Increased levels of fatty acids in diabetes may thus contribute to chronic PKC activation associated with this disorder. PMID:11415460

  14. Fatty acids inhibit growth-factor-induced diacylglycerol kinase alpha activation in vascular smooth-muscle cells.

    PubMed Central

    Du, X; Jiang, Y; Qian, W; Lu, X; Walsh, J P

    2001-01-01

    We have previously shown that unsaturated fatty acids amplify platelet-derived-growth-factor (PDGF)-induced protein kinase C (PKC) activation in vascular smooth-muscle cells (VSMCs). Diacylglycerol-induced PKC activation is normally terminated by diacylglycerol kinases (DGKs). We thus hypothesized that fatty acids act by inhibiting a DGK. Fractionation of VSMC extracts demonstrated that the DGK alpha isoform was the major DGK activity present. PDGF markedly increased the DGK activity of cultured cells. An inhibitor selective for the DGK alpha isoform, R59949 [3-[2-[4-(bis-(4-fluorophenyl)methylene]piperidin-1-yl)ethyl]-2,3-dihydro-2-thioxo-4(1H)-quinazolinone], abolished the growth-factor-induced increase in DGK activity, but had little effect on basal activity. PDGF thus selectively activates DGKalpha. Epidermal growth factor and alpha-thrombin stimulated total DGK activity similarly to PDGF. Activation by epidermal growth factor was sensitive to R59949, again suggesting involvement of DGKalpha. However, the alpha-thrombin-induced activity was unaffected by this agent. Unsaturated fatty acids inhibited growth-factor-induced DGKalpha activation, but had no effect on basal activity. Fatty acids also amplified the PDGF-induced increase in cell diacylglycerol content. These results indicate that inhibition of DGKalpha contributes to fatty-acid-induced amplification of PKC activation. Increased levels of fatty acids in diabetes may thus contribute to chronic PKC activation associated with this disorder. PMID:11415460

  15. The effect of pH on the inhibition of bacterial growth by physiological concentrations of butyric acid: Implications for neonates fed on suckled milk

    Microsoft Academic Search

    Cynthia Q Sun; Charmian J O'Connor; Susan J Turner; Gillian D Lewis; Roger A Stanley; Anthony M Roberton

    1998-01-01

    Butyric acid is released from milk by pre-intestinal lipases during suckling. It is also known to inhibit bacterial growth. To investigate whether butyric acid may be a significant factor in controlling bacterial growth in the stomach of pre-weaned animals, the ability of butyric acid to inhibit growth of selected bacteria was tested over physiological ranges of pH and butyric acid

  16. Use of jasmonic acid and salicylic acid to inhibit growth of sugarbeet storage rot pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Jasmonic acid (JA) and salicylic acid (SA) are endogenous plant hormones that induce native plant defense responses and provide protection against a wide range of diseases. Previously, JA, applied after harvest, was shown to protect sugarbeet roots against the storage pathogens, Botrytis cinerea, P...

  17. Enhanced Lignin Monomer Production Caused by Cinnamic Acid and Its Hydroxylated Derivatives Inhibits Soybean Root Growth

    PubMed Central

    Lima, Rogério Barbosa; Salvador, Victor Hugo; dos Santos, Wanderley Dantas; Bubna, Gisele Adriana; Finger-Teixeira, Aline; Soares, Anderson Ricardo; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and sinapic acids) are known allelochemicals that affect the seed germination and root growth of many plant species. Recent studies have indicated that the reduction of root growth by these allelochemicals is associated with premature cell wall lignification. We hypothesized that an influx of these compounds into the phenylpropanoid pathway increases the lignin monomer content and reduces the root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p-coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and the composition of p-hydroxyphenyl (H), guaiacyl (G) and syringyl (S) monomers. To this end, three-day-old seedlings were cultivated in nutrient solution with or without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid pathway) in a growth chamber for 24 h. In general, the results showed that 1) cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased lignin content; 2) cinnamic and p-coumaric acids increased p-hydroxyphenyl (H) monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl (G) content, and sinapic acid increased sinapyl (S) content; 3) when applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H), cinnamic acid reduced H, G and S contents; and 4) when applied in conjunction with 3,4-(methylenedioxy)cinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL), p-coumaric acid reduced H, G and S contents, whereas caffeic, ferulic and sinapic acids reduced G and S contents. These results confirm our hypothesis that exogenously applied allelochemicals are channeled into the phenylpropanoid pathway causing excessive production of lignin and its main monomers. By consequence, an enhanced stiffening of the cell wall restricts soybean root growth. PMID:24312480

  18. Enhanced lignin monomer production caused by cinnamic Acid and its hydroxylated derivatives inhibits soybean root growth.

    PubMed

    Lima, Rogério Barbosa; Salvador, Victor Hugo; dos Santos, Wanderley Dantas; Bubna, Gisele Adriana; Finger-Teixeira, Aline; Soares, Anderson Ricardo; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and sinapic acids) are known allelochemicals that affect the seed germination and root growth of many plant species. Recent studies have indicated that the reduction of root growth by these allelochemicals is associated with premature cell wall lignification. We hypothesized that an influx of these compounds into the phenylpropanoid pathway increases the lignin monomer content and reduces the root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p-coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and the composition of p-hydroxyphenyl (H), guaiacyl (G) and syringyl (S) monomers. To this end, three-day-old seedlings were cultivated in nutrient solution with or without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid pathway) in a growth chamber for 24 h. In general, the results showed that 1) cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased lignin content; 2) cinnamic and p-coumaric acids increased p-hydroxyphenyl (H) monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl (G) content, and sinapic acid increased sinapyl (S) content; 3) when applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H), cinnamic acid reduced H, G and S contents; and 4) when applied in conjunction with 3,4-(methylenedioxy)cinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL), p-coumaric acid reduced H, G and S contents, whereas caffeic, ferulic and sinapic acids reduced G and S contents. These results confirm our hypothesis that exogenously applied allelochemicals are channeled into the phenylpropanoid pathway causing excessive production of lignin and its main monomers. By consequence, an enhanced stiffening of the cell wall restricts soybean root growth. PMID:24312480

  19. Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells.

    PubMed

    Schley, Patricia D; Jijon, Humberto B; Robinson, Lindsay E; Field, Catherine J

    2005-07-01

    The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells in animal models and cell lines, but the mechanism by which this occurs is not well understood. In order to explore possible mechanisms for the modulation of breast cancer cell growth by omega-3 fatty acids, we examined the effects of EPA and DHA on the human breast cancer cell line MDA-MB-231. Omega-3 fatty acids (a combination of EPA and DHA) inhibited the growth of MDA-MB-231 cells by 30-40% (p<0.05) in both the presence and absence of linoleic acid, an essential omega-6 fatty acid. When provided individually, DHA was more potent than EPA in inhibiting the growth of MDA-MB-231 cells (p<0.05). EPA and DHA treatment decreased tumor cell proliferation (p<0.05), as estimated by decreased [methyl-(3)H]-thymidine uptake and expression of proliferation-associated proteins (proliferating cell nuclear antigen, PCNA, and proliferation-related kinase, PRK). In addition, EPA and DHA induced apoptosis, as indicated by a loss of mitochondrial membrane potential, increased caspase activity and increased DNA fragmentation (p<0.05). Cells incubated with omega-3 fatty acids demonstrated decreased Akt phosphorylation, as well as NFkappaB DNA binding activity (p<0.05). The results of this study indicate that omega-3 fatty acids decrease cell proliferation and induce apoptotic cell death in human breast cancer cells, possibly by decreasing signal transduction through the Akt/NFkappaB cell survival pathway. PMID:15986129

  20. Inhibition of Translation and Bacterial Growth by Peptide Nucleic Acid Targeted to Ribosomal RNA

    Microsoft Academic Search

    Liam Good; Peter E. Nielsen

    1998-01-01

    Peptide nucleic acid (PNA) is a DNA mimic that has shown considerable promise as a lead compound for developing gene therapeutic drugs. We report that PNAs targeted to functional and accessible sites in ribosomal RNA can inhibit translation in an Escherichia coli cell-free transcription\\/translation system, with 50% reductions caused by nanomolar PNA concentrations. The effect in vitro is quantitatively similar

  1. Growth inhibition of putrefactive anaerobe 3679 caused by stringent-type response induced by protonophoric activity of sorbic acid.

    PubMed Central

    Ronning, I E; Frank, H A

    1987-01-01

    The inhibitory effects of potassium sorbate on the bioenergetics, phenylalanine uptake, protein synthesis, and certain aspects of cell regulation were examined in putrefactive anaerobe 3679. Undissociated sorbic acid appeared to act as a protonophore by lowering the intracellular pH and dissipating the proton motive force of the membrane. Sorbate inhibited the uptake of phenylalanine, decreased the rate of protein synthesis, and altered patterns of phosphorylated nucleotide accumulation, resulting in increased intracellular concentrations of GTP, ppGpp, and an unidentified compound (possibly pppGpp). The addition of a noninhibitory amount of tetracycline released the inhibition of growth by sorbate. Based on these results, we concluded that the inhibition of putrefactive anaerobe 3679 by sorbate resulted from a stringent-type regulatory response induced by the protonophoric activity of sorbic acid. PMID:3606088

  2. Gambogic acid induces apoptosis and inhibits colorectal tumor growth via mitochondrial pathways

    PubMed Central

    Huang, Guang-Ming; Sun, Yu; Ge, Xin; Wan, Xin; Li, Chun-Bo

    2015-01-01

    AIM: To investigate the effect of gambogic acid (GA) on apoptosis in the HT-29 human colon cancer cell line. METHODS: H-29 cells were used for in vitro experiments in this study. Relative cell viability was assessed using MTT assays. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling and Hoechst 33342 staining, and quantified by flow cytometry. Cellular ultrastructure was observed by transmission electron microscopy. Real-time PCR and Western blot analyses were used to evaluate gene and protein expression levels. For in vivo experiments, BALB/c nude mice received subcutaneous injections of HT-29 cells in the right armpit. When well-established xenografts were palpable with a tumor size of 75 mm3, mice were randomly assigned to a vehicle (negative) control, positive control or GA treatment group (n = 6 each). The animals in the treatment group received one of three dosages of GA (in saline; 5, 10 or 20 mg/kg) via the caudal vein twice weekly, whereas animals in the negative and positive control groups were given equal volumes of 0.9% saline or 10 mg/kg docetaxel, respectively, via the caudal vein once weekly. RESULTS: The cell viability assay showed that GA inhibited proliferation of HT-29 cells in a dose- and time-dependent manner after treatment with GA (0.00, 0.31, 0.62, 1.25, 2.50, 5.00 or 10.00 ?mol/L) for 24, 48 or 72 h. After 48 h, the percentage of apoptotic cells in cells treated with 0.00, 1.25, 2.50 and 5.00 ?mol/L GA was 1.4% ± 0.3%, 9.8% ± 1.2%, 25.7% ± 3.3% and 49.3% ± 5.8%, respectively. Ultrastructural analysis of HT-29 cells treated for 48 h with 2.5?mol/L GA revealed apoptotic bodies and condensed and fragmented nuclei. Levels of caspase-8, -9 and -3 mRNAs were significantly increased after treatment with GA (1.25, 2.50 or 5.00 ?mol/L) for 48 h (P < 0.05 for all). Protein levels of apoptosis-related factors Fas, FasL, FADD, cytochrome c, and Apaf-1 were increased in GA-treated cells, whereas levels of pro-caspase-8, -9 and -3 were significantly decreased (P < 0.05 for all). Furthermore, GA signi?cantly and dose-dependently inhibited the growth of HT-29 tumors in a mouse xenograft model (P < 0.05). CONCLUSION: GA inhibits HT-29 proliferation via induction of apoptosis. The anti-cancer effects are likely mediated by death receptor (extrinsic) and mitochondrial (intrinsic) pathways.

  3. Fetal hydantoin syndrome: inhibition of placental folic acid transport as a potential mechanism for fetal growth retardation in the rat

    SciTech Connect

    Will, M.; Barnard, J.A.; Said, H.M.; Ghishan, F.K.

    1985-04-01

    Maternal hydantoin ingestion during pregnancy results in a well defined clinical entity termed ''fetal hydantoin syndrome''. The clinical characteristics of this syndrome includes growth retardation, and congenital anomalies. Because folic acid is essential for protein synthesis and growth, and since hydantoin interferes with intestinal transport of folic acid, the authors postulated that part of the fetal hydantoin syndrome may be due to inhibition of placental folic acid by maternal hydantoin. Therefore, they studied in vivo placental folate transport in a well-established model for fetal hydantoin syndrome in the rat. Our results indicate that maternal hydantoin ingestion, significantly decreased fetal weight and placental and fetal uptake of folate compared to controls. To determine whether maternal hydantoin ingestion has a generalized or specific effect on placental function, they examined placental and fetal zinc transport in the same model. Our results indicate that zinc transport is not altered by hydantoin ingestion. They conclude that maternal hydantoin ingestion results in fetal growth retardation which may be due in part to inhibition of placental folate transport.

  4. Abscisic Acid Inhibition of Radicle Emergence But Not Seedling Growth Is Suppressed by Sugars1

    PubMed Central

    Finkelstein, Ruth R.; Lynch, Tim J.

    2000-01-01

    Low concentrations of sugars altered the sensitivity of seed germination to inhibition by exogenous abscisic acid (ABA). Germination of wild-type and ABA-insensitive (abi) Arabidopsis seeds was assayed on media containing ABA and a variety of sugars and sugar alcohols. The inhibitory effects of ABA were strongly repressed in the presence of 15 to 90 mm glucose (Glc), sucrose, or fructose, but not by comparable concentrations of sorbitol or mannitol. Several features of the response to Glc are inconsistent with a purely nutritional effect: The optimal sugar concentration is low and differs between the wild type and the abi mutants. Furthermore, Glc suppression of ABA inhibition is light dependent and limited to the process of radicle emergence. PMID:10759513

  5. Inhibition of trans-retinoic acid-resistant human breast cancer cell growth by retinoid X receptor-selective retinoids.

    PubMed Central

    Wu, Q; Dawson, M I; Zheng, Y; Hobbs, P D; Agadir, A; Jong, L; Li, Y; Liu, R; Lin, B; Zhang, X K

    1997-01-01

    All-trans-retinoic acid (trans-RA) and other retinoids exert anticancer effects through two types of retinoid receptors, the RA receptors (RARs) and retinoid X receptors (RXRs). Previous studies demonstrated that the growth-inhibitory effects of trans-RA and related retinoids are impaired in certain estrogen-independent breast cancer cell lines due to their lower levels of RAR alpha and RARbeta. In this study, we evaluated several synthetic retinoids for their ability to induce growth inhibition and apoptosis in both trans-RA-sensitive and trans-RA-resistant breast cancer cell lines. Our results demonstrate that RXR-selective retinoids, particularly in combination with RAR-selective retinoids, could significantly induce RARbeta and inhibit the growth and induce the apoptosis of trans-RA-resistant, RAR alpha-deficient MDA-MB-231 cells but had low activity against trans-RA-sensitive ZR-75-1 cells that express high levels of RAR alpha. Using gel retardation and transient transfection assays, we found that the effects of RXR-selective retinoids on MDA-MB-231 cells were most likely mediated by RXR-nur77 heterodimers that bound to the RA response element in the RARbeta promoter and activated the RARbeta promoter in response to RXR-selective retinoids. In contrast, growth inhibition by RAR-selective retinoids in trans-RA-sensitive, RAR alpha-expressing cells most probably occurred through RXR-RAR alpha heterodimers that also bound to and activated the RARbeta promoter. In MDA-MB-231 clones stably expressing RAR alpha, both RARbeta induction and growth inhibition by RXR-selective retinoids were suppressed, while the effects of RAR-selective retinoids were enhanced. Together, our results demonstrate that activation of RXR can inhibit the growth of trans-RA-resistant MDA-MB-231 breast cancer cells and suggest that low cellular RAR alpha may regulate the signaling switch from RAR-mediated to RXR-mediated growth inhibition in breast cancer cells. PMID:9343423

  6. Conjugated linoleic acid isomers and their conjugated derivatives inhibit growth of human cancer cell lines.

    PubMed

    De la Torre, Anne; Debiton, Eric; Durand, Denys; Chardigny, Jean-Michel; Berdeaux, Olivier; Loreau, Olivier; Barthomeuf, Chantal; Bauchart, Dominique; Gruffat, Dominique

    2005-01-01

    Conjugated linoleic acid (CLA), mainly c9,t11- and t10,c12-isomers, and polyunsaturated n-3 fatty acids (n-3 PUFA) have been shown to reduce tumor growth. This study compared, on a set of human tumor cells (breast, lung, colon, prostate and melanoma), the antiproliferative effects of: i) trans monounsaturated fatty acids (MUFA) vs. cis MUFA and MUFA vs. PUFA, ii) individual isomers of CLA vs. linoleic acid, iii) CLA-conjugated derivatives vs. their non-conjugated homologues and vs. CLA isomers. Tumor cells were exposed to medium containing individual FA (100 microM) for 48 h and their proliferation was determined by measuring the cellular DNA content (fluorescent Hoechst 33342 dye). The antiproliferative effects of FA varied with the type of cells and were mainly dependent on the degree of unsaturation and on the position and configuration of their double bonds. One isomer of CLA (t9,t11-18:2) and CLA-conjugated derivatives exhibited the strongest growth-inhibitory effect against cancer cells. These results suggest that ruminant products contain active compounds against human tumor cell proliferation. PMID:16309181

  7. Glycyrrhizic acid inhibits leukemia cell growth and migration via blocking AKT/mTOR/STAT3 signaling

    PubMed Central

    He, Si-Qi; Gao, Meng; Fu, Yun-Feng; Zhang, Ya-Nan

    2015-01-01

    Glycyrrhizic acid (GA) is the bioactive compound of licorice and has been used as an herbal medicine because of its anti-viral, anti-cancer, and anti-inflammatory properties. This study was designed to investigate the effects of GA on leukemia cells growth, migration, and the mechanisms underlying the anti-cancer activities of GA. MTT test was used to detect the effect of GA on TF-1 leukemia cell growth. Wound closure assay and Transwell were adopted to assess the effect of GA on TF-1 migration and invasion. Migration and invasion related proteins including AKT and mTOR were detected by western blot assay. We further used western blot and immunofluorescence assay to evaluate the effect of GA on STAT3 phosphorylation in vitro. We also evaluated the anti-tumor effect of GA in TF-1 tumor bearing BALB/c mice model. The present study showed GA significant inhibit of TF-1 proliferation in a dose and time-dependent manner. GA could remarkably inhibit TF-1 cell migration and invasion; meanwhile effectively suppress AKT, mTOR, and STAT3 phosphorylation in TF-1 cells. GA in 100 mg/kg/ could inhibit the tumor growth in vivo and down-regulated AKT, mTOR, and STAT3 phosphorylation in TF-1 tumor tissues. Our findings suggest that GA is a promising therapeutic agent for leukemia that targets the AKT/mTOR/STAT3 pathway. PMID:26191214

  8. Inhibition of apatite crystal growth by the amino-terminal segment of human salivary acidic proline-rich proteins

    Microsoft Academic Search

    T. Aoba; E. C. Moreno; D. I. Hay

    1984-01-01

    Summary  Inhibition of seeded apatitic crystal growth by human salivary acidic proline-rich phosphoproteins (PRP) has been related\\u000a to their adsorption onto the apatite seeds. The amino-terminal 30-residue segment of the PRP makes an important contribution\\u000a to this adsorption. This peptide (PRP1(T1)) and its dephosphorylated analogue from PRP3 (PRP3(T1)DP) were prepared. They have\\u000a identical sequences, except the phosphates at residues 8 and

  9. Betulinic Acid Inhibits Growth of Cultured Vascular Smooth Muscle Cells In Vitro by Inducing G1 Arrest and Apoptosis

    PubMed Central

    Vadivelu, Raja Kumar; Yeap, Swee Keong; Ali, Abdul Manaf; Hamid, Muhajir; Alitheen, Noorjahan Banu

    2012-01-01

    Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC) is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC50 of 3.8??g/mL significantly (P < 0.05). Nevertheless, betulinic acid exhibited G1 cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24?h of treatment. In conclusion, betulinic acid induced G1 cell cycle arrest and dose-dependent DNA damage on VSMC. PMID:23056140

  10. Boric acid destabilizes the hyphal cytoskeleton and inhibits invasive growth of Candida albicans.

    PubMed

    Pointer, Benjamin R; Boyer, Michael P; Schmidt, Martin

    2015-04-01

    Exposure of Candida albicans to sub-lethal concentrations of boric acid (BA) restricts the dimorphic fungus to its yeast morphology and prevents the formation of invasive hyphae on solid substrates. Exposure to BA causes a rapid and reversible disappearance of polarisome and Spitzenkörper in growing hyphae. In BA-treated hyphae of C. albicans, actin quickly reorganizes from cytoplasmic cables to cortical patches and cell wall growth switches from an apical to an isotropic pattern. As a result of the cytoskeletal changes, the hyphal tips broaden and directional growth of hyphae ceases in the presence of BA. An analysis of homozygous deletion strains showed that mutants with constitutive or enhanced hyphal growth (tup1, nrg1, ssn6, rbf1) are BA-sensitive, demonstrating that cellular morphology is a major determinant of BA tolerance. The screening of deletion mutants also showed that deficiencies of the main activator of hyphal gene expression, Efg1, and the Rim101-signalling cascade, leading to Efg1 activation, cause BA resistance. Taken together, the data presented show that the selective inhibitory effect on BA on C. albicans hyphae is rooted in a disruption of apical cytoskeletal elements of growing hyphae. PMID:25612315

  11. Inhibition of apatite crystal growth by the amino-terminal segment of human salivary acidic proline-rich proteins.

    PubMed

    Aoba, T; Moreno, E C; Hay, D I

    1984-12-01

    Inhibition of seeded apatitic crystal growth by human salivary acidic proline-rich phosphoproteins (PRP) has been related to their adsorption onto the apatite seeds. The amino-terminal 30-residue segment of the PRP makes an important contribution to this adsorption. This peptide (PRP1(T1] and its dephosphorylated analogue from PRP3 (PRP3(T1)DP) were prepared. They have identical sequences, except the phosphates at residues 8 and 22 in PRP1(T1) are absent from PRP3(T1)DP. Adsorption of these peptides onto hydroxyapatite and their effect on crystal growth from a defined supersaturated solution was studied. Adsorption behavior was adequately described by the Langmuir adsorption isotherm. The adsorption affinity constant of PRP1(T1) (K = 20,200 ml/mumol) was more than 10 times the corresponding value for PRP3(T1)DP (1,800 ml/mumol), and similar to that of the parent protein, PRP1 (26,200 ml/mumol). Inhibition of crystal growth by the peptides was interpreted in terms of the fractional coverage of the maximum number of adsorption sites (as derived from the adsorption isotherms), suggesting that the molecules block, by adsorption, specific growth sites on these surfaces. Comparison of precipitation kinetics showed that PRP1(T1) is a more effective inhibitor than PRP3(T1)DP at the same initial concentration (10(-6)-10(-7)M). However, on the basis of per mol adsorbed, PRP3(T1)DP displays a greater inhibitory activity; such a behavior is consistent with a more open molecular structure which blocks more growth sites per mol adsorbed than PRP1(T1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6099209

  12. Inhibition of microbial growth and enrichment of gamma-aminobutyric acid during germination of brown rice by electrolyzed oxidizing water.

    PubMed

    Lu, Zhan-Hui; Zhang, Yan; Li, Li-Te; Curtis, Rempel B; Kong, Xiao-Lin; Fulcher, R Gary; Zhang, Gong; Cao, Wei

    2010-03-01

    Electrolyzed oxidizing water (EOW) has been regarded as a potential environmentally friendly broad spectrum microbial decontaminant. EOW with a pH of 3.0 and oxidation reduction potential of 1,079.0 mV were generated by the electrolysis of a dilute NaCl solution (20 mM) in an electrochemical cell. The effects of EOW, 1% NaClO solution, and alkaline electrolyzed water on controlling microbial growth, germination ratio, and enrichment of gamma-aminobutyric acid in germinated brown rice (GBR) were evaluated in this study. Results show that EOW was the most effective at inhibiting microbial growth during germination. Rinsing the rice grains with EOW at 12-h intervals resulted in aerobic plate count reductions of 4.82 log CFU/g, while soaking resulted in bacterial count reductions of 5.38 log CFU/g after 72 h of germination. Moreover, EOW significantly enriched gamma-aminobutyric acid content in GBR (P < 0.05); content was increased 1.6 times in grain rinsed with EOW and 1.8 times in grain soaked in EOW. The findings indicate that EOW is a feasible disinfectant for industrial GBR production. PMID:20202333

  13. Pachymic Acid Inhibits Growth and Induces Apoptosis of Pancreatic Cancer In Vitro and In Vivo by Targeting ER Stress

    PubMed Central

    Cheng, Shujie; Swanson, Kristen; Eliaz, Isaac; McClintick, Jeanette N.; Sandusky, George E.; Sliva, Daniel

    2015-01-01

    Pachymic acid (PA) is a purified triterpene extracted from medicinal fungus Poria cocos. In this paper, we investigated the anticancer effect of PA on human chemotherapy resistant pancreatic cancer. PA triggered apoptosis in gemcitabine-resistant pancreatic cancer cells PANC-1 and MIA PaCa-2. Comparative gene expression array analysis demonstrated that endoplasmic reticulum (ER) stress was induced by PA through activation of heat shock response and unfolded protein response related genes. Induced ER stress was confirmed by increasing expression of XBP-1s, ATF4, Hsp70, CHOP and phospho-eIF2?. Moreover, ER stress inhibitor tauroursodeoxycholic acid (TUDCA) blocked PA induced apoptosis. In addition, 25 mg kg-1 of PA significantly suppressed MIA PaCa-2 tumor growth in vivo without toxicity, which correlated with induction of apoptosis and expression of ER stress related proteins in tumor tissues. Taken together, growth inhibition and induction of apoptosis by PA in gemcitabine-resistant pancreatic cancer cells were associated with ER stress activation both in vitro and in vivo. PA may be potentially exploited for the use in treatment of chemotherapy resistant pancreatic cancer. PMID:25915041

  14. Docosahexaenoic acid inhibits the growth of hormone-dependent prostate cancer cells by promoting the degradation of the androgen receptor.

    PubMed

    Hu, Zhimei; Qi, Haixia; Zhang, Ruixue; Zhang, Kun; Shi, Zhemin; Chang, Yanan; Chen, Linfeng; Esmaeili, Mohsen; Baniahmad, Aria; Hong, Wei

    2015-09-01

    Epidemiological and preclinical data have demonstrated the preventative effects of ?-3 polyunsaturated fatty acids, including docosahexaenoic acid (DHA), on prostate cancer. However, there are inconsistencies in these previous studies and the underlying mechanisms remain to be elucidated. In the present study, the androgen receptor (AR), which is a transcription factor involved in cell proliferation and prostate carcinogenesis, was identified as a target of DHA. It was revealed that DHA inhibited hormone?dependent growth of LNCaP prostate cancer cells. Reverse transcription-quantitative polymerase chain reaction analysis revealed that treatment with DHA caused no alteration in the transcribed mRNA expression levels of the AR gene. However, immunoblotting revealed that this treatment reduces the protein expression level of the AR. The androgen?induced genes were subsequently repressed by treatment with DHA. It was demonstrated that DHA exhibits no effect on the translation process of the AR, however, it promotes the proteasome?mediated degradation of the AR. Therefore, the present study provided a novel mechanism by which DHA exhibits an inhibitory effect on growth of prostate cancer cells. PMID:25997493

  15. Gambogic acid induces growth inhibition and differentiation via upregulation of p21waf1/cip1 expression in acute myeloid leukemia cells.

    PubMed

    Chen, Yan; Hui, Hui; Li, Zheng; Wang, Hong-Mei; You, Qi-Dong; Lu, Na

    2014-10-01

    Gambogic acid (GA) is the major active ingredient of gamboges, a brownish to orange resin product from Garcinia hanburyi tree in Southeast Asia. This compound exhibits anti-cancer effect on solid tumors. In this study, we investigated the effects of GA on the growth and differentiation of acute myeloid leukemia cells by growth-inhibition detection, morphological changes observation, nitroblue tetrazolium reduction, and the expression of the relative cell-surface differentiation markers. The results showed that GA could inhibit cell growth and promote differentiation in U937 and HL-60 cells. In addition, GA upregulated the expression of p21waf1/cip1 in the two cell lines. Finally, downregulating the p21waf1/cip1 expression with small interfering RNA partially blocked GA-induced cell growth inhibition and differentiation. These results of this study revealed that GA may be used as one of the investigational drugs for acute myeloid leukemia. PMID:24835506

  16. Gallic acid inhibits gastric cancer cells metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-?B activity

    SciTech Connect

    Ho, Hsieh-Hsun [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China)] [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Chang, Chi-Sen [Department of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China) [Department of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Division of Gastroenterology, Taichung Veterans General Hospital, Taichung 402, Taiwan (China); Ho, Wei-Chi [Division of Gastroenterology, Jen-Ai Hospital, Taichung 402, Taiwan (China)] [Division of Gastroenterology, Jen-Ai Hospital, Taichung 402, Taiwan (China); Liao, Sheng-You [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China)] [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Lin, Wea-Lung [Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China) [Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pathology, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Wang, Chau-Jong, E-mail: wcj@csmu.edu.tw [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China) [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China)

    2013-01-01

    Our previous study demonstrated the therapeutic potential of gallic acid (GA) for controlling tumor metastasis through its inhibitory effect on the motility of AGS cells. A noteworthy finding in our previous experiment was increased RhoB expression in GA-treated cells. The aim of this study was to evaluate the role of RhoB expression on the inhibitory effects of GA on AGS cells. By applying the transfection of RhoB siRNA into AGS cells and an animal model, we tested the effect of GA on inhibition of tumor growth and RhoB expression. The results confirmed that RhoB-siRNA transfection induced GA to inhibit AGS cells’ invasive growth involving blocking the AKT/small GTPase signals pathway and inhibition of NF-?B activity. Finally, we evaluated the effect of GA on AGS cell metastasis by colonization of tumor cells in nude mice. It showed GA inhibited tumor cells growth via the expression of RhoB. These data support the inhibitory effect of GA which was shown to inhibit gastric cancer cell metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-?B activity. Thus, GA might be a potential agent in treating gastric cancer. Highlights: ? GA could downregulate AKT signal via increased expression of RhoB. ? GA inhibits metastasis in vitro in gastric carcinoma. ? GA inhibits tumor growth in nude mice model.

  17. Growth inhibition of Aeromonas salmonicida and Yersinia ruckeri by disinfectants containing peracetic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid is a therapeutic agent used for disinfection in aquaculture, but it must be investigated thoroughly in order to mitigate diseases without harmful effects to fish. These agents should not leave dangerous residues in the environment in order to successfully contribute to sustainable aq...

  18. Growth inhibition of Aeromonas salmonicida and Yersinia ruckeri by disinfectants containing peracetic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid is a therapeutic agent used for disinfection, but it must be investigated in order to mitigate diseases without harmful effects to the fish. These agents should not leave dangerous residues in the environment in order to successfully contribute to sustainable aquaculture. The aim of ...

  19. Inhibition of smooth muscle cell growth in vitro by an antisense oligodeoxynucleotide released from poly(DL-lactic-co-glycolic acid) microparticles.

    PubMed

    Cleek, R L; Rege, A A; Denner, L A; Eskin, S G; Mikos, A G

    1997-06-15

    We fabricated poly(DL-lactic-co-glycolic acid) (PLGA) 50:50 microparticles loaded with an antisense (AS) oligodeoxy-nucleotide (ODN) against the rat tenascin mRNA and determined the effect in vitro of the AS-ODN released on smooth muscle cell (SMC) proliferation and migration. AS-ODN was entrapped using a double-emulsion-solvent-extraction technique with high efficiency. Release of AS-ODN was characterized by a small initial-burst effect followed by a period of controlled AS-ODN release for up to 20 days. SMC proliferation studies exhibited dose-dependent growth inhibition with AS-ODN-loaded microparticles. Microparticles loaded with scrambled (SC) ODN showed less growth inhibition than AS-ODN. Moreover, only the AS-ODN-loaded microparticles inhibited migration. These results demonstrate the feasibility of entrapping an AS-ODN to rat tenascin in PLGA microparticles for controlled delivery to inhibit SMC proliferation and migration. PMID:9189830

  20. Docosahexaenoic Acid (DHA), a Primary Tumor Suppressive Omega3 Fatty Acid, Inhibits Growth of Colorectal Cancer Independent of p53 Mutational Status

    Microsoft Academic Search

    Taeko Kato; Nicole Kolenic; Ronald S. Pardini

    2007-01-01

    Human colon carcinoma COLO 205, carrying wild type p53, grown subcutaneously in athymic mice was inhibited 80% by a high fat menhaden oil diet containing a mixture of omega-3 fatty acids compared to the low fat corn oil diet containing omega-6 fatty acids. Feeding a high fat diet of golden algae oil containing docosahexaenoic acid (DHA) as the sole long

  1. Ethylene-Induced Inhibition of Root Growth Requires Abscisic Acid Function in Rice (Oryza sativa L.) Seedlings

    PubMed Central

    He, Si-Jie; Lu, Xiang; Zhang, Wan-Ke; Lu, Tie-Gang; Chen, Shou-Yi; Zhang, Jin-Song

    2014-01-01

    Ethylene and abscisic acid (ABA) have a complicated interplay in many developmental processes. Their interaction in rice is largely unclear. Here, we characterized a rice ethylene-response mutant mhz4, which exhibited reduced ethylene-response in roots but enhanced ethylene-response in coleoptiles of etiolated seedlings. MHZ4 was identified through map-based cloning and encoded a chloroplast-localized membrane protein homologous to Arabidopsis thaliana (Arabidopsis) ABA4, which is responsible for a branch of ABA biosynthesis. MHZ4 mutation reduced ABA level, but promoted ethylene production. Ethylene induced MHZ4 expression and promoted ABA accumulation in roots. MHZ4 overexpression resulted in enhanced and reduced ethylene response in roots and coleoptiles, respectively. In root, MHZ4-dependent ABA pathway acts at or downstream of ethylene receptors and positively regulates root ethylene response. This ethylene-ABA interaction mode is different from that reported in Arabidopsis, where ethylene-mediated root inhibition is independent of ABA function. In coleoptile, MHZ4-dependent ABA pathway acts at or upstream of OsEIN2 to negatively regulate coleoptile ethylene response, possibly by affecting OsEIN2 expression. At mature stage, mhz4 mutation affects branching and adventitious root formation on stem nodes of higher positions, as well as yield-related traits. Together, our findings reveal a novel mode of interplay between ethylene and ABA in control of rice growth and development. PMID:25330236

  2. Growth inhibition in clonal subpopulations of a human epithelioid sarcoma cell line by retinoic acid and tumour necrosis factor alpha.

    PubMed Central

    Engers, R.; van Roy, F.; Heymer, T.; Ramp, U.; Moll, R.; Dienst, M.; Friebe, U.; Pohl, A.; Gabbert, H. E.; Gerharz, C. D.

    1996-01-01

    Epithelioid sarcoma is a highly malignant soft tissue tumour that is refractory to conventional chemotherapy and irradiation. Since permanent cell lines of this tumour are extremely rare, in vitro data on compounds with significant antiproliferative effects are still lacking. Therefore, we investigated the effects of retinoic acid (RA) and tumour necrosis factor alpha (TNF-alpha) on tumour cell proliferation of three different clonal subpopulations (GRU-1A, GRU-1B, GRU-1C) derived from the same human epithelioid sarcoma cell line, GRU-1. In GRU-1A both RA (P=0.01) and TNF-alpha (P=0.002) exhibited highly significant and dose-dependent growth inhibitory effects, which could further be increased by a combined application of both compounds (P<0.006). GRU-1B proved to be sensitive to RA (P=0.006), whereas no response to TNF-alpha was observed. GRU-1C was resistant to both RA and TNF-alpha. The antiproliferative effect of TNF-alpha was mediated by TNF receptor 1(TNF-R1) and correlated positively with both the number of TNF-R1 per cell and receptor affinity. No correlation was detected between RA-induced growth inhibition and the expression pattern of the RA receptors (RARs) RAR-alpha, RAR-beta, and RAR-gamma. Plating efficiency, however, could exclusively be reduced by RA in GRU-1B, the only cell line expressing RAR-alpha. Taken together, these data are the first showing significant antiproliferative effects in human epithelioid sarcoma by RA and TNF-alpha. Whereas the TNF-alpha response seems to depend on the expression of TNF-R1, no simple correlation could be found between RA sensitivity and the expression pattern of RARs. Images Figure 1 Figure 3 PMID:8595164

  3. Glycyrrhetinic Acid Inhibits Cell Growth and Induces Apoptosis in Ovarian Cancer A2780 Cells

    PubMed Central

    Haghshenas, Venus; Fakhari, Shohreh; Mirzaie, Sako; Rahmani, Mohammadreza; Farhadifar, Fariba; Pirzadeh, Sara; Jalili, Ali

    2014-01-01

    Purpose:Accumulating evidence indicates that glycyrrhizin (GZ) and its hydrolyzed metabolite 18-? glycyrrhetinic acid (GA) exhibit anti-inflammatory and anticancer activities. The objective of this study was to examine the in vitro cytotoxic activity of GA on human ovarian cancer A2780 cells. Methods: A2780 cells were cultured in RPMI1640 containing 10% fetal bovine serum. Cells were treated with different doses of GA and cell viability and proliferation were detected by dye exclusion and 3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assays. Apoptosis induction and expression of Fas and Fas ligand (FasL) were analyzed by flow cytometry. Results: We observed that GA decreases cell viability and suppressed cells proliferation in a dose-dependent manner as detected by dye-exclusion and XTT assayes. In addition, our flow cytometry data show that GA not only induces apoptosis in A2780 cells but also upregulates both Fas and FasL on these cells in a dose-dependent manner. Conclusion: we demonstrate that GA causes cell death in A2780 cells by inducing apoptosis. PMID:25364659

  4. STAT3-independent inhibition of lysophosphatidic acid-mediated upregulation of connective tissue growth factor (CTGF) by cucurbitacin I

    Microsoft Academic Search

    Angela Graness; Valeria Poli; Margarete Goppelt-Struebe

    2006-01-01

    Cucurbitacins are recognised as anti-tumour agents because of their interference with STAT3 signalling, but may also affect the integrity of the actin cytoskeleton. In the present study the effect of cucurbitacin I was investigated in fibroblasts. In these cells, cucurbitacin I interfered with lysophosphatidic acid (LPA) signalling. It inhibited tyrosine phosphorylation of focal adhesion proteins and induction of connective tissue

  5. Perlwapin, an abalone nacre protein with three four-disulfide core (whey acidic protein) domains, inhibits the growth of calcium carbonate crystals.

    PubMed

    Treccani, Laura; Mann, Karlheinz; Heinemann, Fabian; Fritz, Monika

    2006-10-01

    We have isolated a new protein from the nacreous layer of the shell of the sea snail Haliotis laevigata (abalone). Amino acid sequence analysis showed the protein to consist of 134 amino acids and to contain three sequence repeats of approximately 40 amino acids which were very similar to the well-known whey acidic protein domains of other proteins. The new protein was therefore named perlwapin. In addition to the major sequence, we identified several minor variants. Atomic force microscopy was used to explore the interaction of perlwapin with calcite crystals. Monomolecular layers of calcite crystals dissolve very slowly in deionized water and recrystallize in supersaturated calcium carbonate solution. When perlwapin was dissolved in the supersaturated calcium carbonate solution, growth of the crystal was inhibited immediately. Perlwapin molecules bound tightly to distinct step edges, preventing the crystal layers from growing. Using lower concentrations of perlwapin in a saturated calcium carbonate solution, we could distinguish native, active perlwapin molecules from denaturated ones. These observations showed that perlwapin can act as a growth inhibitor for calcium carbonate crystals in saturated calcium carbonate solution. The function of perlwapin in nacre growth may be to inhibit the growth of certain crystallographic planes in the mineral phase of the polymer/mineral composite nacre. PMID:16861275

  6. Conjugated Linoleic Acid (CLA) Inhibits Expression of the Spot 14 (THRSP) and Fatty Acid Synthase Genes and Impairs the Growth of Human Breast Cancer and Liposarcoma Cells

    Microsoft Academic Search

    Christina Donnelly; Arne M. Olsen; Lionel D. Lewis; Burton L. Eisenberg; Alan Eastman; William B. Kinlaw

    2008-01-01

    Spot 14 (THRSP, S14) is a nuclear protein involved in the regulation of genes required for fatty acid synthesis in normal and malignant mammary epithelial and adipose cells. Harvatine and Bauman (1) reported that conjugated linoleic acid (CLA) inhibits S14 gene expression in bovine mammary and mouse adipose tissues and reduces milk fat production in cows. We hypothesized that CLA

  7. Epoxyeicosatrienoic acids induce growth inhibition and calpain\\/caspase-12 dependent apoptosis in PDGF cultured 3T6 fibroblast

    Microsoft Academic Search

    Diana Nieves; Juan J. Moreno

    2007-01-01

    Previous studies have demonstrated that arachidonic acid (AA) metabolites released by the cyclooxygenase pathway is involved\\u000a in serum-induced 3T6 fibroblast cycle progression and proliferation. However, these results also suggest that other AA cascade\\u000a pathways might be involved. Recently, we also described the role of hydroxyeicosatetraenoic acids, which are produced by cytochrome\\u000a P450 monooxygenases (CYP), in 3T6 fibroblast growth. AA can

  8. Naringenin inhibits seed germination and seedling root growth through a salicylic acid-independent mechanism in Arabidopsis thaliana.

    PubMed

    Hernández, Iker; Munné-Bosch, Sergi

    2012-12-01

    Flavonoids fulfill an enormous range of biological functions in plants. In seeds, these compounds play several roles; for instance proanthocyanidins protect them from moisture, pathogen attacks, mechanical stress, UV radiation, etc., and flavonols have been suggested to protect the embryo from oxidative stress. The present study aimed at determining the role of flavonoids in Arabidopsis thaliana (L.) seed germination, and the involvement of salicylic acid (SA) and auxin (indole-3-acetic acid), two phytohormones with the same biosynthetic origin as flavonoids, the shikimate pathway, in such a putative role. We show that naringenin, a flavanone, strongly inhibits the germination of A. thaliana seeds in a dose-dependent and SA-independent manner. Altered auxin levels do not affect seed germination in Arabidopsis, but impaired auxin transport does, although to a minor extent. Naringenin and N-1-naphthylphthalamic acid (NPA) impair auxin transport through the same mechanisms, so the inhibition of germination by naringenin might involve impaired auxin transport among other mechanisms. From the present study it is concluded that naringenin inhibits the germination of Arabidopsis seeds in a dose-dependent and SA-independent manner, and the results also suggest that such effects are exerted, at least to some extent, through impaired auxin transport, although additional mechanisms seem to operate as well. PMID:23031844

  9. Docosahexaenoic acid from a cultured microalga inhibits cell growth and induces apoptosis by upregulating Bax/Bcl-2 ratio in human breast carcinoma MCF-7 cells.

    PubMed

    Chiu, Lawrence C-M; Wong, Elaine Y-L; Ooi, Vincent E C

    2004-12-01

    Docosahexaenoic acid (DHA) is an omega-3 fatty acid that comprises 22 carbons and 6 alternative double bonds in its hydrocarbon chain (22:6omega3). Previous studies have shown that DHA from fish oil controls the growth and development of different cancers; however, safety issues have been raised repeatedly about contamination of toxins in fish oil that makes it no longer a clean and safe source of the fatty acid. We investigated the cell growth inhibition of DHA from the cultured microalga Crypthecodinium cohnii (algal DHA [aDHA]) in human breast carcinoma MCF-7 cells. aDHA exhibited growth inhibition on breast cancer cells dose-dependently by 16.0% to 59.0% of the control level after 72-h incubations with 40 to 160 microM of the fatty acid. DNA flow cytometry shows that aDHA induced sub-G(1) cells, or apoptotic cells, by 64.4% to 171.3% of the control levels after incubations with 80 mM of the fatty acid for 24, 48, and 72 h. Western blot studies further show that aDHA did not modulate the expression of proapoptotic Bax protein but induced the downregulation of anti-apoptotic Bcl-2 expression time-dependently, causing increases of Bax/Bcl-2 ratio by 303.4% and 386.5% after 48- and 72-h incubations respectively with the fatty acid. Results from this study suggest that DHA from the cultured microalga is also effective in controlling cancer cell growth and that downregulation of antiapoptotic Bcl-2 is an important step in the induced apoptosis. PMID:15659818

  10. Mechanism of Growth Inhibition of Human Cancer Cells by Conjugated Eicosapentaenoic Acid, an Inhibitor of DNA Polymerase and Topoisomerase

    PubMed Central

    Yonezawa, Yuko; Yoshida, Hiromi; Mizushina, Yoshiyuki

    2007-01-01

    DNA topoisomerases (topos) and DNA polymerases (pols) are involved in many aspects of DNA metabolism such as replication reactions. We found that long chain unsaturated fatty acids such as polyunsaturated fatty acids (PUFA) (i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) inhibited the activities of eukaryotic pols and topos in vitro, and the inhibitory effect of conjugated fatty acids converted from EPA and DHA (cEPA and cDHA) on pols and topos was stronger than that of normal EPA and DHA. cEPA and cDHA did not affect the activities of plant and prokaryotic pols or other DNA metabolic enzymes tested. cEPA was a stronger inhibitor than cDHA with IC50 values for mammalian pols and human topos of 11.0 – 31.8 and 0.5 – 2.5 ?M, respectively. cEPA inhibited the proliferation of two human leukemia cell lines, NALM-6, which is a p53-wild type, and HL-60, which is a p53-null mutant, and the inhibitory effect was stronger than that of normal EPA. In both cell lines, cEPA arrested in the G1 phase, and increased cyclin E protein levels, indicating that it blocks the primary step of in vivo DNA replication by inhibiting the activity of replicative pols rather than topos. DNA replication-related proteins, such as RPA70, ATR and phosphorylated-Chk1/2, were increased by cEPA treatment in the cell lines, suggesting that cEPA led to DNA replication fork stress inhibiting the activities of pols and topos, and the ATR-dependent DNA damage response pathway could respond to the inhibitor of DNA replication. The compound induced cell apoptosis through both p53-dependent and p53-independent pathways in cell lines NALM-6 and HL-60, respectively. These results suggested the therapeutic potential of conjugated PUFA, such as cEPA, as a leading anti-cancer compound that inhibited pols and topos activities.

  11. Salvianolic acid A positively regulates PTEN protein level and inhibits growth of A549 lung cancer cells

    PubMed Central

    BI, LEI; CHEN, JIANPING; YUAN, XIAOJING; JIANG, ZEQUN; CHEN, WEIPING

    2013-01-01

    Salvianolic acid A (Sal A) is an effective compound extracted from Salvia miltiorrhiza which has been used in the treatment of various diseases. Preliminary data indicate that Sal A treatment has a specific anti-lung cancer effect. However, the manner in which Sal A regulates cancer growth remains unknown. In this study, the A549 lung cancer cell line and its response to Sal A treatment was examined. Results showed that Sal A treatment significantly decreased A549 cell growth, promoted partial apoptosis and increased mitochondrial membrane permeability. Western blot analysis showed that Sal A upregulated the phosphatase and tensin homolog (PTEN) protein level, while consistently downregulating Akt phosphorylation. These results indicate that Sal A negatively mediates A549 lung cancer cell line growth or apoptosis, most likely by positively regulating PTEN protein level. PMID:24648921

  12. Ursolic Acid Inhibits Growth and Metastasis of Human Colorectal Cancer in an Orthotopic Nude Mouse Model by Targeting Multiple Cell Signaling Pathways: Chemosensitization with Capecitabine

    PubMed Central

    Prasad, Sahdeo; Yadav, Vivek R.; Sung, Bokyung; Reuter, Simone; Kannappan, Ramaswamy; Deorukhkar, Amit; Diagaradjane, Parmeswaran; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Krishnan, Sunil; Guha, Sushovan; Aggarwal, Bharat B.

    2013-01-01

    Purpose Development of chemoresistance, poor prognosis, and metastasis often renders the current treatments for colorectal cancer (CRC) ineffective. Whether ursolic acid (UA), a component of numerous medicinal plants, either alone or in combination with capecitabine, can inhibit the growth and metastasis of human CRC was investigated. Experimental design The effect of UA on proliferation of colorectal cancer cell lines was examined by mitochondrial dye-uptake assay, apoptosis by esterase staining, NF-?B activation by DNA binding assay and protein expression by western blot. The effect of UA on the growth and chemosensitization was also examined in orthotopically-implanted CRC in nude mice. Results We found that UA inhibited the proliferation of different colon cancer cell lines. This is correlated with inhibition of constitutive NF-?B activation and downregulation of cell survival (Bcl-xL, Bcl-2, cFLIP, survivin), proliferative (Cyclin D1), and metastatic (MMP-9, VEGF, ICAM-1) proteins. When examined in an orthotopic nude-mice model, UA significantly inhibited tumor volume, ascites formation and distant organ metastasis, and this effect was enhanced with capecitabine. Immunohistochemistry of tumor tissue indicated that UA downregulated biomarkers of proliferation (Ki-67) and microvessel density (CD31). This effect was accompanied by suppression of NF-?B, STAT3, and ?-catenin. In addition, UA suppressed EGFR, and induced p53, and p21 expression. We also observed bioavailability of UA in the serum and tissue of animals. Conclusion Overall our results demonstrate that UA can inhibit the growth and metastasis of CRC and further enhance the therapeutic effects of capecitabine through suppression of multiple biomarkers linked to inflammation, proliferation, invasion, angiogenesis, and metastasis. PMID:22832932

  13. Short-chain fatty acids inhibit growth hormone and prolactin gene transcription via cAMP/PKA/CREB signaling pathway in dairy cow anterior pituitary cells.

    PubMed

    Wang, Jian-Fa; Fu, Shou-Peng; Li, Su-Nan; Hu, Zhong-Ming; Xue, Wen-Jing; Li, Zhi-Qiang; Huang, Bing-Xu; Lv, Qing-Kang; Liu, Ju-Xiong; Wang, Wei

    2013-01-01

    Short-chain fatty acids (SCFAs) play a key role in altering carbohydrate and lipid metabolism, influence endocrine pancreas activity, and as a precursor of ruminant milk fat. However, the effect and detailed mechanisms by which SCFAs mediate bovine growth hormone (GH) and prolactin (PRL) gene transcription remain unclear. In this study, we detected the effects of SCFAs (acetate, propionate, and butyrate) on the activity of the cAMP/PKA/CREB signaling pathway, GH, PRL, and Pit-1 gene transcription in dairy cow anterior pituitary cells (DCAPCs). The results showed that SCFAs decreased intracellular cAMP levels and a subsequent reduction in PKA activity. Inhibition of PKA activity decreased CREB phosphorylation, thereby inhibiting GH and PRL gene transcription. Furthermore, PTX blocked SCFAs- inhibited cAMP/PKA/CREB signaling pathway. These data showed that the inhibition of GH and PRL gene transcription induced by SCFAs is mediated by Gi activation and that propionate is more potent than acetate and butyrate in inhibiting GH and PRL gene transcription. In conclusion, this study identifies a biochemical mechanism for the regulation of SCFAs on bovine GH and PRL gene transcription in DCAPCs, which may serve as one of the factors that regulate pituitary function in accordance with dietary intake. PMID:24177567

  14. A mechanism of growth inhibition by abscisic acid in germinating seeds of Arabidopsis thaliana based on inhibition of plasma membrane H+-ATPase and decreased cytosolic pH, K+, and anions

    PubMed Central

    Planes, María D.; Niñoles, Regina; Rubio, Lourdes; Bissoli, Gaetano; Bueso, Eduardo; García-Sánchez, María J.; Alejandro, Santiago; Gonzalez-Guzmán, Miguel; Hedrich, Rainer; Rodriguez, Pedro L.; Fernández, José A.; Serrano, Ramón

    2015-01-01

    The stress hormone abscisic acid (ABA) induces expression of defence genes in many organs, modulates ion homeostasis and metabolism in guard cells, and inhibits germination and seedling growth. Concerning the latter effect, several mutants of Arabidopsis thaliana with improved capability for H+ efflux (wat1-1D, overexpression of AKT1 and ost2-1D) are less sensitive to inhibition by ABA than the wild type. This suggested that ABA could inhibit H+ efflux (H+-ATPase) and induce cytosolic acidification as a mechanism of growth inhibition. Measurements to test this hypothesis could not be done in germinating seeds and we used roots as the most convenient system. ABA inhibited the root plasma-membrane H+-ATPase measured in vitro (ATP hydrolysis by isolated vesicles) and in vivo (H+ efflux from seedling roots). This inhibition involved the core ABA signalling elements: PYR/PYL/RCAR ABA receptors, ABA-inhibited protein phosphatases (HAB1), and ABA-activated protein kinases (SnRK2.2 and SnRK2.3). Electrophysiological measurements in root epidermal cells indicated that ABA, acting through the PYR/PYL/RCAR receptors, induced membrane hyperpolarization (due to K+ efflux through the GORK channel) and cytosolic acidification. This acidification was not observed in the wat1-1D mutant. The mechanism of inhibition of the H+-ATPase by ABA and its effects on cytosolic pH and membrane potential in roots were different from those in guard cells. ABA did not affect the in vivo phosphorylation level of the known activating site (penultimate threonine) of H+-ATPase in roots, and SnRK2.2 phosphorylated in vitro the C-terminal regulatory domain of H+-ATPase while the guard-cell kinase SnRK2.6/OST1 did not. PMID:25371509

  15. Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivo via cyclooxygenase-2 and apoptotic pathways.

    PubMed

    Hao, Yubin; Xie, Tianpei; Korotcov, Alexandru; Zhou, Yanfei; Pang, Xiaowu; Shan, Liang; Ji, Hongguang; Sridhar, Rajagopalan; Wang, Paul; Califano, Joseph; Gu, Xinbin

    2009-05-01

    Overexpression of cyclooxygenase-2 (COX-2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a nonsteroidal anti-inflammatory drug, which inhibits COX-2 but not COX-1. This selective COX-2 inhibitor holds promise as a cancer preventive agent. Concerns about cardiotoxicity of celecoxib, limits its use in long-term chemoprevention and therapy. Salvianolic acid B (Sal-B) is a leading bioactive component of Salvia miltiorrhiza Bge, which is used for treating neoplastic and chronic inflammatory diseases in China. The purpose of this study was to investigate the mechanisms by which Sal-B inhibits HNSCC growth. Sal-B was isolated from S. miltiorrhiza Bge by solvent extraction followed by 2 chromatographic steps. Pharmacological activity of Sal-B was assessed in HNSCC and other cell lines by estimating COX-2 expression, cell viability and caspase-dependent apoptosis. Sal-B inhibited growth of HNSCC JHU-022 and JHU-013 cells with IC(50) of 18 and 50 microM, respectively. Nude mice with HNSCC solid tumor xenografts were treated with Sal-B (80 mg/kg/day) or celecoxib (5 mg/kg/day) for 25 days to investigate in vivo effects of the COX-2 inhibitors. Tumor volumes in Sal-B treated group were significantly lower than those in celecoxib treated or untreated control groups (p < 0.05). Sal-B inhibited COX-2 expression in cultured HNSCC cells and in HNSCC cells isolated from tumor xenografts. Sal-B also caused dose-dependent inhibition of prostaglandin E(2) synthesis, either with or without lipopolysaccharide stimulation. Taken together, Sal-B shows promise as a COX-2 targeted anticancer agent for HNSCC prevention and treatment. PMID:19123475

  16. N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth.

    PubMed

    Cao, Wenqing; Ma, ZhiFan; Rasenick, Mark M; Yeh, ShuYan; Yu, JiangZhou

    2012-01-01

    Although evidence has shown the regulating effect of n-3 poly-unsaturated fatty acid (n-3 PUFA) on cell signaling transduction, it remains unknown whether n-3 PUFA treatment modulates estrogen signaling. The current study showed that docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) shifted the pro-survival and proliferative effect of estrogen to a pro-apoptotic effect in human breast cancer (BCa) MCF-7 and T47D cells. 17 ?-estradiol (E2) enhanced the inhibitory effect of n-3 PUFAs on BCa cell growth. The IC50 of DHA or EPA in MCF-7 cells decreased when combined with E2 (10 nM) treatment (from 173 µM for DHA only to 113 µM for DHA+E2, and from 187 µm for EPA only to 130 µm for EPA+E2). E2 also augmented apoptosis in n-3 PUFA-treated BCa cells. In contrast, in cells treated with stearic acid (SA, C18:0) as well as cells not treated with fatty acid, E2 promoted breast cancer cell growth. Classical (nuclear) estrogen receptors may not be involved in the pro-apoptotic effects of E2 on the n-3 PUFA-treated BCa cells because ER? agonist failed to elicit, and ER? knockdown failed to block E2 pro-apoptotic effects. Subsequent studies reveal that G protein coupled estrogen receptor 1 (GPER1) may mediate the pro-apoptotic effect of estrogen. N-3 PUFA treatment initiated the pro-apoptotic signaling of estrogen by increasing GPER1-cAMP-PKA signaling response, and blunting EGFR, Erk 1/2, and AKT activity. These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment. PMID:23285198

  17. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

    PubMed Central

    2011-01-01

    Background Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NF?B, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent. PMID:21864401

  18. Aromatic hydrocarbon receptor inhibits lysophosphatidic acid-induced vascular endothelial growth factor-A expression in PC-3 prostate cancer cells

    SciTech Connect

    Wu, Pei-Yi; Lin, Yueh-Chien; Lan, Shun-Yan [Institute of Zoology, National Taiwan University, Taipei, Taiwan (China)] [Institute of Zoology, National Taiwan University, Taipei, Taiwan (China); Huang, Yuan-Li [Department of Biotechnology, Asia University, Taichung, Taiwan (China)] [Department of Biotechnology, Asia University, Taichung, Taiwan (China); Lee, Hsinyu, E-mail: hsinyu@ntu.edu.tw [Institute of Zoology, National Taiwan University, Taipei, Taiwan (China) [Institute of Zoology, National Taiwan University, Taipei, Taiwan (China); Department of Life Science, National Taiwan University, Taipei, Taiwan (China)

    2013-08-02

    Highlights: •LPA-induced VEGF-A expression was regulated by HIF-1? and ARNT. •PI3K mediated LPA-induced VEGF-A expression. •AHR signaling inhibited LPA-induced VEGF-A expression in PC-3 cells. -- Abstract: Lysophosphatidic acid (LPA) is a lipid growth factor with multiple biological functions and has been shown to stimulate cancer cell secretion of vascular endothelial growth factor-A (VEGF-A) and trigger angiogenesis. Hypoxia-inducible factor-1 (HIF-1), a heterodimer consisting of HIF-1? and HIF-1? (also known as aromatic hydrocarbon receptor nuclear translocator (ARNT)) subunits, is an important regulator of angiogenesis in prostate cancer (PC) through the enhancement of VEGF-A expression. In this study, we first confirmed the ability of LPA to induce VEGF-A expression in PC-3 cells and then validated that LPA-induced VEGF-A expression was regulated by HIF-1? and ARNT through phosphatidylinositol 3-kinase activation. Aromatic hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with ARNT and was found to inhibit prostate carcinogenesis and vanadate-induced VEGF-A production. Since ARNT is a common dimerization partner of AHR and HIF-1?, we hypothesized that AHR might suppress LPA-induced VEGF-A expression in PC-3 cells by competing with HIF-1? for ARNT. Here we demonstrated that overexpression and ligand activation of AHR inhibited HIF-1-mediated VEGF-A induction by LPA treatment of PC-3 cells. In conclusion, our results suggested that AHR activation may inhibit LPA-induced VEGF-A expression in PC-3 cells by attenuating HIF-1? signaling, and subsequently, suppressing angiogenesis and metastasis of PC. These results suggested that AHR presents a potential therapeutic target for the prevention of PC metastasis.

  19. Combination effects of salvianolic acid B with low-dose celecoxib on inhibition of head and neck squamous cell carcinoma growth in vitro and in vivo.

    PubMed

    Zhao, Yuan; Hao, Yubin; Ji, Hongguang; Fang, Yayin; Guo, Yinhan; Sha, Wei; Zhou, Yanfei; Pang, Xiaowu; Southerland, William M; Califano, Joseph A; Gu, Xinbin

    2010-06-01

    Head and neck squamous cell carcinoma (HNSCC) development is closely associated with inflammation. Cyclooxygenase-2 (COX-2) is an important mediator of inflammation. Therefore, celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib, but it seems likely that this may be diminished by lowering its dose. We found that salvianolic acid B (Sal-B), isolated from Salvia miltiorrhiza Bge, can effectively suppress COX-2 expression and induce apoptosis in a variety of cancer cell lines. In this study, we report that combination of Sal-B with low-dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. The combination effects were assessed in four HNSCC cell lines (JHU-06, JHU-011, JHU-013, and JHU-022) by evaluating cell viability, proliferation, and tumor xenograft growth. Cell viability and proliferation were significantly inhibited by both the combined and single-agent treatments. However, the combination treatment significantly enhanced anticancer efficacy in JHU-013 and JHU-022 cell lines compared with the single treatment regimens. A half-dose of daily Sal-B (40 mg/kg/d) and celecoxib (2.5 mg/kg/d) significantly inhibited JHU-013 xenograft growth relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was associated with profound inhibition of COX-2 and enhanced induction of apoptosis. Taken together, these results strongly suggest that combination of Sal-B, a multifunctional anticancer agent, with low-dose celecoxib holds potential as a new preventive strategy in targeting inflammatory-associated tumor development. PMID:20501859

  20. Antisense growth inhibition of methicillin-resistant Staphylococcus aureus by locked nucleic acid conjugated with cell-penetrating peptide as a novel FtsZ inhibitor.

    PubMed

    Meng, Jingru; Da, Fei; Ma, Xue; Wang, Ning; Wang, Yukun; Zhang, Huinan; Li, Mingkai; Zhou, Ying; Xue, Xiaoyan; Hou, Zheng; Jia, Min; Luo, Xiaoxing

    2015-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections are becoming increasingly difficult to treat, owing to acquired antibiotic resistance. The emergence and spread of MRSA limit therapeutic options and require new therapeutic strategies, including novel MRSA-active antibiotics. Filamentous temperature-sensitive protein Z (FtsZ) is a highly conserved bacterial tubulin homologue that is essential for controlling the bacterial cell division process in different species of S. aureus. We conjugated a locked nucleic acid (LNA) that targeted ftsZ mRNA with the peptide (KFF)3K, to generate peptide-LNA (PLNA). The present study aimed to investigate whether PLNA could be used as a novel antibacterial agent. PLNA787, the most active agent synthesized, exhibited promising inhibitory effects on four pathogenic S. aureus strains in vitro. PLNA787 inhibited bacterial growth and resolved lethal Mu50 infections in epithelial cell cultures. PLNA787 also improved the survival rates of Mu50-infected mice and was associated with reductions of bacterial titers in several tissue types. The inhibitory effects on ftsZ mRNA and FtsZ protein expression and inhibition of the bacterial cell division process are considered to be the major mechanisms of PLNA. PLNA787 demonstrated activity against MRSA infections in vitro and in vivo. Our findings suggest that ftsZ mRNA is a promising new target for developing novel antisense antibiotics. PMID:25421468

  1. Salicylic acid alleviates cadmium-induced inhibition of growth and photosynthesis through upregulating antioxidant defense system in two melon cultivars (Cucumis melo L.).

    PubMed

    Zhang, Yongping; Xu, Shuang; Yang, Shaojun; Chen, Youyuan

    2015-05-01

    Cadmium (Cd) is a widespread toxic heavy metal that usually causes deleterious effects on plant growth and development. Salicylic acid (SA), a naturally existing phenolic compound, is involved in specific responses to various environmental stresses. To explore the role of SA in the tolerance of melon (Cucumis melo L.) to Cd stress, the influence of SA application on the growth and physiological processes was compared in the two melon cultivars Hamilv (Cd-tolerant) and Xiulv (Cd-sensitive) under Cd stress. Under 400-?M Cd treatment, Hamilv showed a higher biomass accumulation, more chlorophyll (Chl), greater photosynthesis, and less oxidative damage compared to Xiulv. Foliar spraying of 0.1 mM SA dramatically alleviated Cd-induced growth inhibition in the two melon genotypes. Simultaneously, SA pretreatment attenuated the decrease in Chl content, photosynthetic capacity, and PSII photochemistry efficiency in Cd-stressed plants. Furthermore, exogenous SA significantly reduced superoxide anion production and lipid peroxidation, followed by increase in the activities of antioxidant enzyme superoxide dismutase, guaiacol peroxidase, catalase, and ascorbate peroxidase, and content of soluble protein and free proline in both the genotypes under Cd stress. The effect of SA was more conspicuous in Xiulv than Hamilv, reflected in the biomass, photosynthetic pigments, stomatal conductance, water use efficiency, and antioxidant enzymes. These results suggest that exogenous spray of SA can alleviate the adverse effects of Cd on the growth and photosynthesis of both the melon cultivars, mostly through promoting antioxidant defense capacity. It also indicates that SA-included protection against Cd damage is to a greater extent more pronounced in Cd-sensitive genotype than Cd-tolerant genotype. PMID:25398649

  2. Connexin-dependent gap junction enhancement is involved in the synergistic effect of sorafenib and all-trans retinoic acid on HCC growth inhibition

    PubMed Central

    YANG, YAN; QIN, SHU-KUI; WU, QIONG; WANG, ZI-SHU; ZHENG, RONG-SHENG; TONG, XU-HUI; LIU, HAO; TAO, LIANG; HE, XIAN-DI

    2014-01-01

    Increasing gap junction activity in tumor cells provides a target by which to enhance antineoplastic therapies. Previously, several naturally occurring agents, including all-trans retinoic acid (ATRA) have been demonstrated to increase gap junctional intercellular communication (GJIC) in a number of types of cancer cells. In the present study, we investigated in vitro whether ATRA modulates the response of human hepatocellular carcinoma (HCC) cells to sorafenib, the only proven oral drug for advanced HCC, and the underlying mechanisms. HepG2 and SMMC-7721 cells were treated with sorafenib and/or ATRA, and cell proliferation and apoptosis were analyzed; the role of GJIC was also explored. We found that ATRA, at non-toxic concentrations, enhanced sorafenib-induced growth inhibition in both HCC cell lines, and this effect was abolished by two GJIC inhibitors, 18-?-GA and oleamide. Whereas lower concentrations of sorafenib (5 ?M) or ATRA (0.1 or 10 ?M) alone modestly induced GJIC activity, the combination of sorafenib plus ATRA resulted in a strong enhancement of GJIC. However, the action paradigm differed in the HepG2 and SMMC-7721 cells, with the dominant effect of GJIC dependent on the cell-specific connexin increase in protein amounts and relocalization. RT-PCR assay further revealed a transcriptional modification of the key structural connexin in the two cell lines. Thus, a connexin-dependent gap junction enhancement may play a central role in ATRA plus sorafenib synergy in inhibiting HCC cell growth. Since both agents are available for human use, the combination treatment represents a future profitable strategy for the treatment of advanced HCC. PMID:24317203

  3. Connexin-dependent gap junction enhancement is involved in the synergistic effect of sorafenib and all-trans retinoic acid on HCC growth inhibition.

    PubMed

    Yang, Yan; Qin, Shu-Kui; Wu, Qiong; Wang, Zi-Shu; Zheng, Rong-Sheng; Tong, Xu-Hui; Liu, Hao; Tao, Liang; He, Xian-Di

    2014-02-01

    Increasing gap junction activity in tumor cells provides a target by which to enhance antineoplastic therapies. Previously, several naturally occurring agents, including all-trans retinoic acid (ATRA) have been demonstrated to increase gap junctional intercellular communication (GJIC) in a number of types of cancer cells. In the present study, we investigated in vitro whether ATRA modulates the response of human hepatocellular carcinoma (HCC) cells to sorafenib, the only proven oral drug for advanced HCC, and the underlying mechanisms. HepG2 and SMMC-7721 cells were treated with sorafenib and/or ATRA, and cell proliferation and apoptosis were analyzed; the role of GJIC was also explored. We found that ATRA, at non-toxic concentrations, enhanced sorafenib-induced growth inhibition in both HCC cell lines, and this effect was abolished by two GJIC inhibitors, 18-?-GA and oleamide. Whereas lower concentrations of sorafenib (5 µM) or ATRA (0.1 or 10 µM) alone modestly induced GJIC activity, the combination of sorafenib plus ATRA resulted in a strong enhancement of GJIC. However, the action paradigm differed in the HepG2 and SMMC-7721 cells, with the dominant effect of GJIC dependent on the cell-specific connexin increase in protein amounts and relocalization. RT-PCR assay further revealed a transcriptional modification of the key structural connexin in the two cell lines. Thus, a connexin-dependent gap junction enhancement may play a central role in ATRA plus sorafenib synergy in inhibiting HCC cell growth. Since both agents are available for human use, the combination treatment represents a future profitable strategy for the treatment of advanced HCC. PMID:24317203

  4. Inhibition of Calcium Oxalate Crystal Growth in vitro by Uropontin: Another Member of the Aspartic Acid-Rich Protein Superfamily

    Microsoft Academic Search

    H. Shiraga; W. Min; W. J. Vandusen; M. D. Clayman; D. Miner; C. H. Terrell; J. R. Sherbotie; J. W. Foreman; C. Przysiecki; E. G. Neilson; J. R. Hoyer

    1992-01-01

    The majority of human urinary stones are primarily composed of calcium salts. Although normal urine is frequently supersaturated with respect to calcium oxalate, most humans do not form stones. Inhibitors are among the multiple factors that may influence the complex process of urinary stone formation. We have isolated an inhibitor of calcium oxalate crystal growth from human urine by monoclonal

  5. Well having inhibited microbial growth

    DOEpatents

    Lee, Brady D.; Dooley, Kirk J.

    2006-08-15

    The invention includes methods of inhibiting microbial growth in a well. A packing material containing a mixture of a first material and an antimicrobial agent is provided to at least partially fill a well bore. One or more access tubes are provided in an annular space around a casing within the well bore. The access tubes have a first terminal opening located at or above a ground surface and have a length that extends from the first terminal opening at least part of the depth of the well bore. The access tubes have a second terminal opening located within the well bore. An antimicrobial material is supplied into the well bore through the first terminal opening of the access tubes. The invention also includes well constructs.

  6. Inhibition of Gene Expression and Growth by Antisense Peptide Nucleic Acids in a Multiresistant  -Lactamase-Producing Klebsiella pneumoniae Strain

    Microsoft Academic Search

    Prathiba Kurupati; K. S. W. Tan; G. Kumarasinghe; C. L. Poh

    2007-01-01

    Klebsiella pneumoniae causes common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance. The emergence and spread of -lactamase-producing K. pneumoniae strains highlight the need to develop new therapeutic strategies. In this study, we developed antisense peptide nucleic acids (PNAs) conjugated to the (KFF)3K peptide and investigated whether they could mediate gene-specific antisense effects in K.

  7. Epidermal growth factor inhibits radioiodine uptake but stimulates deoxyribonucleic acid synthesis in newborn rat thyroids grown in nude mice

    SciTech Connect

    Ozawa, S.; Spaulding, S.W. (Buffalo Veterans Administration Medical Center, NY (USA))

    1990-08-01

    We have studied the effect of altering the level of circulating epidermal growth factor (EGF) on the function and growth of newborn rat thyroids transplanted into nude mice. Preliminary studies confirmed that sialoadenectomy reduced circulating EGF levels in nude mice (from 0.17 +/- 0.02 to 0.09 +/- 0.02 ng/ml), and that ip injection of 5 micrograms EGF raised EGF levels (the peak level of 91.7 +/- 3.3 ng/ml was achieved at 30 min, with a subsequent half-life of about 1 h). The radioiodine uptake by newborn rat thyroid transplants in the sialoadenectomized and sham-operated animals correlated inversely with the circulating EGF levels determined when the mice were killed (r = -0.99). Low-dose TSH treatment (0.1 microU/day) generally stimulated the radioiodine uptake, but high-dose TSH groups (100 microU/day) were not significantly different from the control group. The 5-day nuclear (3H)thymidine labeling index was 6.8 +/- 0.5% IN newborn rat thyroid transplants grown in sialoadenectomized animals, 13.1 +/- 0.3% in sham-operated animals, and 16.8 +/- 0.5% in nude mice receiving 5 micrograms EGF ip daily. In general, both low-dose and high-dose TSH promoted DNA synthesis under low EGF conditions but were ineffective in the presence of higher levels of EGF. Adult rat thyroid transplants showed no significant responses. Although sialoadenectomy may alter other factors besides EGF, it appears that changes in the levels of circulating EGF within the physiological range affect the function and growth of newborn rat thyroid transplants. Circulating EGF may play a role in thyroid maturation and may also be involved in the regulation of thyroid function throughout life.

  8. The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth of Erwinia amylovora and acts as a seed germination-arrest factor.

    PubMed

    Lee, Xiaoyun; Azevedo, Mark D; Armstrong, Donald J; Banowetz, Gary M; Reimmann, Cornelia

    2013-02-01

    The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB) shares biological activities with 4-formylaminooxyvinylglycine, a related molecule produced by Pseudomonas fluorescens WH6. We found that culture filtrates of a P.?aeruginosa strain overproducing AMB weakly interfered with seed germination of the grassy weed Poa annua and strongly inhibited growth of Erwinia amylovora, the causal agent of the devastating orchard crop disease known as fire blight. AMB was active against a 4-formylaminooxyvinylglycine-resistant isolate of E.?amylovora, suggesting that the molecular targets of the two oxyvinylglycines in Erwinia do not, or not entirely, overlap. The AMB biosynthesis and transport genes were shown to be organized in two separate transcriptional units, ambA and ambBCDE, which were successfully expressed from IPTG-inducible tac promoters in the heterologous host P.?fluorescens CHA0. Engineered AMB production enabled this model biocontrol strain to become inhibitory against E.?amylovora and to weakly interfere with the germination of several graminaceous seeds. We conclude that AMB production requires no additional genes besides ambABCDE and we speculate that their expression in marketed fire blight biocontrol strains could potentially contribute to disease control. PMID:23757135

  9. Inhibition and Facilitation of Nucleic Acid Amplification

    Microsoft Academic Search

    IAN G. WILSON

    1997-01-01

    Factors that inhibit the amplification of nucleic acids by PCR are present with target DNAs from many sources. The inhib- itors generally act at one or more of three essential points in the reaction in the following ways: they interfere with the cell lysis necessary for extraction of DNA, they interfere by nucleic acid degradation or capture, and they inhibit

  10. The reaction of flavanols with nitrous acid protects against N-nitrosamine formation and leads to the formation of nitroso derivatives which inhibit cancer cell growth.

    PubMed

    Lee, Stephanie Y H; Munerol, Bibiana; Pollard, Susan; Youdim, Kuresh A; Pannala, Ananth S; Kuhnle, Gunter G C; Debnam, Edward S; Rice-Evans, Catherine; Spencer, Jeremy P E

    2006-01-15

    Studies have suggested that diets rich in polyphenols such as flavonoids may lead to a reduced risk of gastrointestinal cancers. We demonstrate the ability of monomeric and dimeric flavanols to scavenge reactive nitrogen species derived from nitrous acid. Both epicatechin and dimer B2 (epicatechin dimer) inhibited nitrous acid-induced formation of 3-nitrotyrosine and the formation of the carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and dimeric epicatechin with nitrous acid led to the formation of mono- and di-nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the formation of nitrated products. Although, epicatechin was transferred across the jejunum of the small intestine yielding metabolites, its nitroso form was not absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of, and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3 activation and reductions in Akt phosphorylation, suggesting activation of apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also induced significant toxic effects in Caco-2 cells. The inhibitory effects on cellular proliferation were paralleled by early inhibition of ERK 1/2 phosphorylation and later reductions in cyclin D1 levels, indicating modulation of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes in which dietary derived flavanols may exert beneficial effects in the gastrointestinal tract. PMID:16413414

  11. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

    SciTech Connect

    Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Roelofs, Hennie M.J.; Morsche, Rene H.M. te [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marian, Brigitte [Institute of Cancer Research, Wien University, Vienna (Austria)] [Institute of Cancer Research, Wien University, Vienna (Austria); Nagengast, Fokko M.; Peters, Wilbert H.M. [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)] [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-04-15

    Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

  12. Heat-stress induced inhibition in growth and chlorosis in mungbean ( Phaseolus aureus Roxb.) is partly mitigated by ascorbic acid application and is related to reduction in oxidative stress

    Microsoft Academic Search

    Ramanpreet Kaur; Navneet Kaur; Kalpna Bhandhari; Neeru Kaushal; Kriti Gupta; T. S. Bains; Harsh Nayyar

    The rising temperatures (>35°C) are proving detrimental to summer-sown mungbean genotypes that experience inhibition of vegetative\\u000a and reproductive growth. In the present study, the mungbean plants growing hydroponically at varying temperatures of 30\\/20°C\\u000a (control), 35\\/25, 40\\/30, and 45\\/35°C (as day\\/night 12 h\\/12 h) with (50 ?M) or without ascorbic acid (ASC) were investigated\\u000a for effects on growth, membrane damage, chlorophyll loss, leaf water

  13. Retinoic acid inhibits airway smooth muscle cell migration

    Microsoft Academic Search

    Regina M. Day; Young H. Lee; Ah-Mee Park; Yuichiro J. Suzuki

    2006-01-01

    Airway remodeling in chronic asthma is characterized by increased smooth muscle mass that is associated with the reduction of the bronchial lumen as well as airway hyperresponsiveness. The devel- opment of agents that inhibit smooth muscle growth is therefore of interest for therapy to prevent asthma-associated airway remod- eling. All-trans retinoic acid (ATRA) suppresses growth of vascular smooth muscle cells(SMCs)

  14. Nickel inhibits mitochondrial fatty acid oxidation.

    PubMed

    Uppala, Radha; McKinney, Richard W; Brant, Kelly A; Fabisiak, James P; Goetzman, Eric S

    2015-08-01

    Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation-the pathway by which fatty acids are catabolized for energy-in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with l-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 h), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1? (HIF1?). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1? knockout fibroblasts, implicating HIF1? as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

  15. Theobromine Inhibits Uric Acid Crystallization. A Potential Application in the Treatment of Uric Acid Nephrolithiasis

    PubMed Central

    Grases, Felix; Rodriguez, Adrian; Costa-Bauza, Antonia

    2014-01-01

    Purpose To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. Materials and Methods The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. Results The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Conclusions Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis. PMID:25333633

  16. Inhibition of elongation growth by two sesquiterpene lactones isolated from Helianthus annuus L

    Microsoft Academic Search

    Otmar Spring; Achim Hager

    1982-01-01

    Two sesquiterpene lactones belonging to the germacranolides were isolated from the leaves and stems of Helianthus annuus L. Their formation in the plant is light-dependent. Both sesquiterpene lactones (SL) strongly inhibit indole-3-acetic acid (IAA)-induced elongation growth of Avena sativa L. coleoptile segments and Helianthus annuus L. hypocotyl segments. Both SL do not, however, inhibit acid-induced growth nor growth triggered by

  17. Luteolin, ellagic acid and punicic acid are natural products that inhibit prostate cancer metastasis.

    PubMed

    Wang, Lei; Li, Wenfang; Lin, Muqing; Garcia, Monika; Mulholland, David; Lilly, Michael; Martins-Green, Manuela

    2014-10-01

    Prostate cancer (PCa) is the second cause of cancer deaths in men in the USA. When the cancer recurs, early stages can be controlled with hormone ablation therapy to delay the rate of cancer progression but, over time, the cancer overcomes its hormone dependence, becomes highly aggressive and metastasizes. Clinical trials have shown that pomegranate juice (PJ) inhibits PCa progression. We have previously shown that the PJ components luteolin (L), ellagic acid (E) and punicic acid (P) together inhibit growth of hormone-dependent and -independent PCa cells and inhibit their migration and chemotaxis towards CXCL12, a chemokine that is important in PCa metastasis. On the basis of these findings, we hypothesized that L+E+P inhibit PCa metastasis in vivo. To test this possibility, we used a severe combined immunodeficiency mouse model in which luciferase-expressing human PCa cells were injected subcutaneously near the prostate. Tumor progression was monitored with bioluminescence imaging weekly. We found that L+E+P inhibits PC-3M-luc primary tumor growth, inhibits the CXCL12/CXCR4 axis for metastasis and none of the tumors metastasized. In addition, L+E+P significantly inhibits growth and metastasis of highly invasive Pten (-/-) ;K-ras (G12D) prostate tumors. Furthermore, L+E+P inhibits angiogenesis in vivo, prevents human endothelial cell (EC) tube formation in culture and disrupts preformed EC tubes, indicating inhibition of EC adhesion to each other. L+E+P also inhibits the angiogenic factors interleukin-8 and vascular endothelial growth factor as well as their induced signaling pathways in ECs. In conclusion, these results show that L+E+P inhibits PCa progression and metastasis. PMID:25023990

  18. Inhibition of bacterial activity in acid mine drainage

    NASA Astrophysics Data System (ADS)

    Singh, Gurdeep; Bhatnagar, Miss Mridula

    1988-12-01

    Acid mine drainage water give rise to rapid growth and activity of an iron- and sulphur- oxidizing bacterium Thiobacillus ferrooxidians which greatly accelerate acid producing reactions by oxidation of pyrite material associated with coal and adjoining strata. The role of this bacterium in production of acid mine drainage is described. This study presents the data which demonstrate the inhibitory effect of certain organic acids, sodium benzoate, sodium lauryl sulphate, quarternary ammonium compounds on the growth of the acidophilic aerobic autotroph Thiobacillus ferrooxidians. In each experiment, 10 milli-litres of laboratory developed culture of Thiobacillus ferrooxidians was added to 250 milli-litres Erlenmeyer flask containing 90 milli-litres of 9-k media supplemented with FeSO4 7H2O and organic compounds at various concentrations. Control experiments were also carried out. The treated and untreated (control) samples analysed at various time intervals for Ferrous Iron and pH levels. Results from this investigation showed that some organic acids, sodium benzoate, sodium lauryl sulphate and quarternary ammonium compounds at low concentration (10-2 M, 10-50 ppm concentration levels) are effective bactericides and able to inhibit and reduce the Ferrous Iron oxidation and acidity formation by inhibiting the growth of Thiobacillus ferrooxidians is also discussed and presented

  19. Dietary linoleic acid, immune inhibition and disease

    PubMed Central

    Sammon, A.

    1999-01-01

    Review of the evidence available in published literature supports a radical change in viewpoint with respect to disease in countries where maize is the predominant dietary component. In these countries, the pattern of disease is largely determined by a change in immune profile caused by metabolites of dietary linoleic acid. High intake of linoleic acid in a diet deficient in other polyunsaturated fatty acids and in riboflavin results in high tissue production of prostaglandin E2, which in turn causes inhibition of the proliferation and cytokine production of Th1 cells, mediators of cellular immunity. Tuberculosis, measles, hepatoma, secondary infection in HIV and kwashiorkor are all favoured by this reduction in cellular immunity. Diet-associated inhibition of the Th1 subset is a major contributor to the high prevalence of these diseases found in areas of sub-Saharan Africa where maize is the staple.???Keywords: maize; linoleic acid; prostaglandin E2; cellular immunity; kwashiorkor; diet PMID:10448487

  20. Inhibition of Citrobacter freundii by lactic acid, ascorbic acid, citric acid, Thymus vulgaris extract and NaCl at 31 °C and 5 °C

    Microsoft Academic Search

    Bayan M. Abu-Ghazaleh

    2006-01-01

    Citrobacter freundii has been implicated in food spoilage and food poisoning outbreaks. This study examines the effects of some compounds (e.g.\\u000a citric acid, ascorbic acid, lactic acid, sodium chloride, andThymus vulgaris extract) on growth of two strains of Citrobacter freundii at 31 °C and 5 °C. At 31 °C, lactic acid (0.2%) or ascorbic acid\\u000a (0.2%) alone completely inhibited growth

  1. Inhibition of oxidative degradation of hyaluronic acid by uric acid.

    PubMed

    Liu, K M; Swann, D; Lee, P; Lam, K W

    1984-08-01

    It has been postulated that glycosaminoglycans in the trabeculum have an influence on aqueous humor drainage. Ascorbate reduces the viscosity of hyaluronic acid, and also increases outflow facility. Our recent observation of high urate concentrations in some glaucomatous eyes led us to study the influence of urate on oxidative degradation of hyaluronic acid by ascorbate. The viscosity of rooster comb hyaluronic acid was reduced slowly by ascorbate. Cupric sulfate accelerated ascorbate oxidation and also enhanced hyaluronic acid degradation. Urate inhibited ascorbate oxidation and prevented the copper catalyzed oxidative degradation of rooster comb hyaluronic acid. The range of urate concentrations used in this study was within the range of urate concentrations observed in glaucomatous eyes. The partially purified umbilical cord hyaluronic acid had lower viscosity than rooster comb hyaluronic acid, and rapidly degraded in the presence of ascorbate. The ascorbate effect on umbilical cord hyaluronic acid was partially prevented by urate. PMID:6488856

  2. Boric acid inhibits human prostate cancer cell proliferation

    Microsoft Academic Search

    Wade T. Barranco; Curtis D. Eckhert

    2004-01-01

    The role of boron in biology includes coordinated regulation of gene expression in mixed bacterial populations and the growth and proliferation of higher plants and lower animals. Here we report that boric acid, the dominant form of boron in plasma, inhibits the proliferation of prostate cancer cell lines, DU-145 and LNCaP, in a dose-dependent manner. Non-tumorigenic prostate cell lines, PWR-1E

  3. Selenoxides inhibit ?-aminolevulinic acid dehydratase

    Microsoft Academic Search

    Marcelo Farina; Vanderlei Folmer; Rodrigo C Bolzan; Leandro H Andrade; Gilson Zeni; Antônio L Braga; João B. T Rocha

    2001-01-01

    The effect of two selenides and their selenoxides on ?-aminolevulinic acid dehydratase (?-ALA-D) from liver of adult rats was investigated. In vivo, selenides can be oxidized to selenoxides by flavin-containing monooxygenases (FMO) and selenoxides can regenerate selenides by thiol oxidation. Phenyl methyl selenide (PhSeCH3) and 1-hexynyl methyl selenide (C4H9C?CSeCH3) were converted to selenoxides by reaction with H2O2. PhSeCH3 and C4H9C?CSeCH3

  4. Inhibition of Vascularization in Tumor Growth

    NASA Astrophysics Data System (ADS)

    Scalerandi, M.; Sansone, B. Capogrosso

    2002-11-01

    The transition to a vascular phase is a prerequisite for fast tumor growth. During the avascular phase, the neoplasm feeds only from the (relatively few) existing nearby blood vessels. During angiogenesis, the number of capillaries surrounding and infiltrating the tumor increases dramatically. A model which includes physical and biological mechanisms of the interactions between the tumor and vascular growth describes the avascular-vascular transition. Numerical results agree with clinical observations and predict the influence of therapies aiming to inhibit the transition.

  5. Fatty acid protection from palmitic acid-induced apoptosis is lost following PI3-kinase inhibition

    Microsoft Academic Search

    N. Beeharry; J. A. Chambers; I. C. Green

    2004-01-01

    We have previously shown that saturated fatty acids induce DNA damage and cause apoptotic cell death in insulin-producing ß-cells. Here we examine further the effects of single or combined dietary fatty acids on RINm5F survival or cell death signalling. Palmitate and stearate, but not linoleate, oleate or palmitoylmethyl ester, induced growth inhibition and increased apoptosis in RINm5F cells following 24

  6. Understanding biocatalyst inhibition by carboxylic acids

    PubMed Central

    Jarboe, Laura R.; Royce, Liam A.; Liu, Ping

    2013-01-01

    Carboxylic acids are an attractive biorenewable chemical in terms of their flexibility and usage as precursors for a variety of industrial chemicals. It has been demonstrated that such carboxylic acids can be fermentatively produced using engineered microbes, such as Escherichia coli and Saccharomyces cerevisiae. However, like many other attractive biorenewable fuels and chemicals, carboxylic acids become inhibitory to these microbes at concentrations below the desired yield and titer. In fact, their potency as microbial inhibitors is highlighted by the fact that many of these carboxylic acids are routinely used as food preservatives. This review highlights the current knowledge regarding the impact that saturated, straight-chain carboxylic acids, such as hexanoic, octanoic, decanoic, and lauric acids can have on E. coli and S. cerevisiae, with the goal of identifying metabolic engineering strategies to increase robustness. Key effects of these carboxylic acids include damage to the cell membrane and a decrease of the microbial internal pH. Certain changes in cell membrane properties, such as composition, fluidity, integrity, and hydrophobicity, and intracellular pH are often associated with increased tolerance. The availability of appropriate exporters, such as Pdr12, can also increase tolerance. The effect on metabolic processes, such as maintaining appropriate respiratory function, regulation of Lrp activity and inhibition of production of key metabolites such as methionine, are also considered. Understanding the mechanisms of biocatalyst inhibition by these desirable products can aid in the engineering of robust strains with improved industrial performance. PMID:24027566

  7. Method of inhibiting corrosion in acidizing wells

    SciTech Connect

    Williams, D.A.; Holifield, P.K.; Looney, J.R.; McDougall, L.A.

    1992-02-18

    This patent describes improvement in a method of acidizing a subterranean formation penetrated by a borehole which has metal pipe positioned therein wherein an aqueous acid solution is pumped down the pipe and into the formation. The improvement comprises introducing components of a nonacetylenic corrosion inhibitor directly into the aqueous acid solution to form the corrosion inhibitor in the acid solution at a concentration to inhibit corrosion of the metal, the components consisting essentially of: an antimony compound which provides from 0.04 to 2.0 wt % of antimony ions in the aqueous acid; from 0.2 to 10 wt % of a quaternary ammonium compound capable of forming a complex with the antimony ions; and from 0.1 to 25 wt % of a surfactant capable of water wetting the pipe.

  8. Inhibition of DNA synthesis of melanoma cells by azelaic acid.

    PubMed

    Leibl, H; Stingl, G; Pehamberger, H; Korschan, H; Konrad, K; Wolff, K

    1985-11-01

    Azelaic acid was successfully used in the clinical treatment of 7 cases of lentigo maligna in that remission of the lesions was observed in all our patients. In order to elucidate mechanism(s) of the beneficial clinical effects, we studied the effect of azelaic acid on cultured melanoma cells. Cell numbers recovered from melanoma cell cultures grown for several days in the presence of 10 mM azelaic acid were 50-70% less than those recovered from control cultures or from cultures containing 10 mM adipic acid. This reduction of cell numbers was not due to a simple cytotoxic or cytolytic effect of azelaic acid but rather due to a dose-dependent inhibition of DNA synthesis. Interestingly, nontoxic concentrations of azelaic acid, which significantly reduced DNA synthesis of cultured melanoma cells, had no overt effect on the protein synthesis of these cells. It is conceivable that inhibition of DNA synthesis is one of the mechanisms by which azelaic acid prevents growth and proliferation of abnormal melanocytes. PMID:4056455

  9. Menaquinone Analogs Inhibit Growth of Bacterial Pathogens

    PubMed Central

    Merriman, Joseph A.; Salgado-Pabón, Wilmara; Mueller, Elizabeth A.; Spaulding, Adam R.; Vu, Bao G.; Chuang-Smith, Olivia N.; Kohler, Petra L.; Kirby, John R.

    2013-01-01

    Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and Streptococcus agalactiae at concentrations of 10 to 200 ?g/ml. Coenzyme Q1 reduced the ability of S. aureus to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit S. aureus growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents. PMID:23959313

  10. Menaquinone analogs inhibit growth of bacterial pathogens.

    PubMed

    Schlievert, Patrick M; Merriman, Joseph A; Salgado-Pabón, Wilmara; Mueller, Elizabeth A; Spaulding, Adam R; Vu, Bao G; Chuang-Smith, Olivia N; Kohler, Petra L; Kirby, John R

    2013-11-01

    Gram-positive bacteria cause serious human illnesses through combinations of cell surface and secreted virulence factors. We initiated studies with four of these organisms to develop novel topical antibacterial agents that interfere with growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4-naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and Streptococcus agalactiae at concentrations of 10 to 200 ?g/ml. Coenzyme Q1 reduced the ability of S. aureus to cause toxic shock syndrome in a rabbit model, inhibited the growth of four Gram-negative bacteria, and synergized with another antimicrobial agent, glycerol monolaurate, to inhibit S. aureus growth. The staphylococcal two-component system SrrA/B was shown to be an antibacterial target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic reactive oxygen species and affect bacterial plasma membranes and biosynthetic machinery to interfere with two-component systems, respiration, and macromolecular synthesis. These compounds represent a novel class of potential topical therapeutic agents. PMID:23959313

  11. Recovery of gibberellic acid inhibition of betacyanin biosynthesis by pigment precursors

    Microsoft Academic Search

    M. M. Laloraya; H. N. Srivastav; K. N. Guruprasad

    1976-01-01

    Gibberellic acid inhibition of betacyanin biosynthesis has been studied in Amaranthus caudatus L. using the pigment precursors L-tyrosine and L-dihydroxyphenylalanine. Precursors fed to gibberellic acid (GA) treated seedlings completely recovered betacyanin synthesis while the GA induced growth enhancement remained unaltered. Inhibition of betacyanin biosynthesis by GA is related to depletion of metabolites\\/amino acids and their diversion to support changed pattern

  12. Lipoproteins inhibit macrophage activation by lipoteichoic acid

    Microsoft Academic Search

    Carl Grunfeld; Maureen Marshall; Judy K. Shigenaga; Arthur H. Moser; Peter Tobias; Kenneth R. Feingold

    Regulation of lipid metabolism during infection is thought to be part of host defense, as lipoproteins neu- tralize endotoxin (LPS) and viruses. Gram-positive infec- tions also induce disturbances in lipid metabolism. There- fore, we investigated whether lipoproteins could inhibit the toxic effects of lipoteichoic acid (LTA), a fragment of gram- positive bacteria. LTA activated RAW264.7 macrophage cells, stimulating production of

  13. Galactose inhibits auxin-induced growth of Avena coleoptiles by two mechanisms

    NASA Technical Reports Server (NTRS)

    Cheung, S. P.; Cleland, R. E.

    1991-01-01

    Galactose inhibits auxin-induced growth of Avena coleoptiles by at least two mechanisms. First, it inhibits auxin-induced H(+)-excretion needed for the initiation of rapid elongation. Galactose cannot be doing so by directly interfering with the ATPase since fusicoccin-induced H(+)-excretion is not affected. Secondly, galactose inhibits long-term auxin-induced growth, even in an acidic (pH 4.5) solution. This may be due to an inhibition of cell wall synthesis. However, galactose does not reduce the capacity of walls to be loosened by H+, given exogenously or excreted in response to fusicoccin.

  14. Acid growth effects in maize roots: Evidence for a link between auxin-economy and proton extrusion in the control of root growth

    Microsoft Academic Search

    M. M. Moloney; M. C. Elliott; R. E. Cleland

    1981-01-01

    The role of proton excretion in the growth of apical segments of maize roots has been examined. Growth is stimulated by acidic buffers and inhibited by neutral buffers. Organic buffers such as 2[N-morpholino] ethane sulphonic acid (MES) — 2-amino-2-(hydroxymethyl)propane-1,3 diol (Tris) are more effective than phosphate buffers in inhibiting growth. Fusicoccin(FC)-induced growth is also inhibited by neutral buffers. The antiauxins

  15. In vitro algal growth inhibition by phytotoxins of Typha latifolia L

    Microsoft Academic Search

    G. Aliotta; M. Della Greca; P. Monaco; G. Pinto; A. Pollio; L. Previtera

    1990-01-01

    The ether extract ofTypha latifolia L. inhibited the growth of some microalgae. Among the substances chromatographically isolated and characterized from the ether extract, three steroids [ß-sitosterol, (20S) 24-methylenlophenol, and stigmast-4-ene-3,6-dione] and three fatty acids [a- linolenic, linoleic, and an unidentified C8:2] were found to inhibit the growth of some microalgae tested. A selective effect of these substance on blue-green algae

  16. A New Growth Inhibitor, Pisumin, Involved in Light Inhibition of Epicotyl Growth of Dwarf Peas

    PubMed Central

    Hasegawa, Koji; Koreeda, M.; Hase, T.

    1983-01-01

    A new growth inhibitor, tentatively named pisumin, which increased under red light and remained at initial level or decreased when dwarf pea (Pisum sativum L. cv Progress No. 9) seedlings were transferred from red light to dark, has been isolated in the form of a colorless powder from light-exposed epicotyls of dwarf peas, and characterized partially as an aliphatic carboxylic acid (molecular weight 284) by spectrometric analyses. Exogenous pisumin inhibited the growth of epicotyl segments of dwarf peas at concentrations higher than 0.1 millimolar in the dark. PMID:16663012

  17. Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis

    PubMed Central

    Zhang, Guodong; Panigrahy, Dipak; Hwang, Sung Hee; Yang, Jun; Mahakian, Lisa M.; Wettersten, Hiromi I.; Liu, Jun-Yan; Wang, Yanru; Ingham, Elizabeth S.; Tam, Sarah; Kieran, Mark W.; Weiss, Robert H.; Ferrara, Katherine W.; Hammock, Bruce D.

    2014-01-01

    Prostaglandins derived from the cyclooxygenase (COX) pathway and epoxyeicosatrienoic acids (EETs) from the cytochrome P450/soluble epoxide hydrolase (sEH) pathway are important eicosanoids that regulate angiogenesis and tumorigenesis. COX-2 inhibitors, which block the formation of prostaglandins, suppress tumor growth, whereas sEH inhibitors, which increase endogenous EETs, stimulate primary tumor growth and metastasis. However, the functional interactions of these two pathways in cancer are unknown. Using pharmacological inhibitors as probes, we show here that dual inhibition of COX-2 and sEH synergistically inhibits primary tumor growth and metastasis by suppressing tumor angiogenesis. COX-2/sEH dual pharmacological inhibitors also potently suppress primary tumor growth and metastasis by inhibiting tumor angiogenesis via selective inhibition of endothelial cell proliferation. These results demonstrate a critical interaction of these two lipid metabolism pathways on tumorigenesis and suggest dual inhibition of COX-2 and sEH as a potential therapeutic strategy for cancer therapy. PMID:25024195

  18. Role of volatile acids in development of the cecal microflora in broilers chickens during growth

    Microsoft Academic Search

    Wielen van der P. W. J. J; STEEF BIESTERVELD; S. Notermans; H. Hofstra; B. A. P. Urlings; F. van Knapen

    2000-01-01

    It is known that volatile fatty acids can inhibit growth of species of the family Enterobacteriaceae in vitro. However, whether these volatile fatty acids affect bacterial populations in the ceca of chickens is unknown. Therefore, a study was conducted to investigate if changes in volatile fatty acids in ceca of broiler chickens during growth affect bacterial populations. Results showed that

  19. Fatty acids modulate transforming growth factor-  activity and plasma clearance

    Microsoft Academic Search

    Thai-Yen Ling; Yen-Hua Huang; Ming-Chih Lai; Shuan Shian Huang; Jung San

    2003-01-01

    The activity and plasma clearance of transforming growth factor (TGF)-? are known to be regulated by activated ?2-macroglobulin (?2M*). This has been implicated in pathophysiological processes, but no small molecule compounds have been reported to modulate TGF-? activity by affecting the interaction of TGF-? and ?2M*. Here, we demonstrate that fatty acids are capable of inhibiting complex formation of TGF-?

  20. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo

    NASA Astrophysics Data System (ADS)

    Kim, K. Jin; Li, Bing; Winer, Jane; Armanini, Mark; Gillett, Nancy; Phillips, Heidi S.; Ferrara, Napoleone

    1993-04-01

    THE development of new blood vessels (angiogenesis) is required for many physiological processes including embryogenesis, wound healing and corpus luteum formation1,2. Blood vessel neoformation is also important in the pathogenesis of many disorders1-5, particularly rapid growth and metastasis of solid tumours3-5. There are several potential mediators of tumour angiogenesis, including basic and acidic fibroblast growth factors, tumour necrosis factor-? and transforming factors-? and -? 1,2. But it is unclear whether any of these agents actually mediates angiogenesis and tumour growth in vivo. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and an angiogenesis inducer released by a variety of tumour cells and expressed in human tumours in situ. To test whether VEGF may be a tumour angiogenesis factor in vivo, we injected human rhabdomyosar-coma, glioblastoma multiforme or leiomyosarcoma cell lines into nude mice. We report here that treatment with a monoclonal antibody specific for VEGF inhibited the growth of the tumours, but had no effect on the growth rate of the tumour cells In vitro. The density of vessels was decreased in the antibody-treated tumours. These findings demonstrate that inhibition of the action of an angiogenic factor spontaneously produced by tumour cells may suppress tumour growth in vivo.

  1. Caffeic acid phenethyl ester induced cell cycle arrest and growth inhibition in androgen-independent prostate cancer cells via regulation of Skp2, p53, p21Cip1 and p27Kip1

    PubMed Central

    Su, Liang-Cheng; Jiang, Shih Sheng; Chan, Tzu-Min; Chang, Chung-Ho; Chen, Li-Tzong; Kung, Hsing-Jien; Wang, Horng-Dar; Chuu, Chih-Pin

    2015-01-01

    Prostate cancer (PCa) patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant prostate cancer (CRPC) within 1–3 years. Treatment with caffeic acid phenethyl ester (CAPE) suppressed cell survival and proliferation via induction of G1 or G2/M cell cycle arrest in LNCaP 104-R1, DU-145, 22Rv1, and C4–2 CRPC cells. CAPE treatment also inhibited soft agar colony formation and retarded nude mice xenograft growth of LNCaP 104-R1 cells. We identified that CAPE treatment significantly reduced protein abundance of Skp2, Cdk2, Cdk4, Cdk7, Rb, phospho-Rb S807/811, cyclin A, cyclin D1, cyclin H, E2F1, c-Myc, SGK, phospho-p70S6kinase T421/S424, phospho-mTOR Ser2481, phospho-GSK3? Ser21, but induced p21Cip1, p27Kip1, ATF4, cyclin E, p53, TRIB3, phospho-p53 (Ser6, Ser33, Ser46, Ser392), phospho-p38 MAPK Thr180/Tyr182, Chk1, Chk2, phospho-ATM S1981, phospho-ATR S428, and phospho-p90RSK Ser380. CAPE treatment decreased Skp2 and Akt1 protein expression in LNCaP 104-R1 tumors as compared to control group. Overexpression of Skp2, or siRNA knockdown of p21Cip1, p27Kip1, or p53 blocked suppressive effect of CAPE treatment. Co-treatment of CAPE with PI3K inhibitor LY294002 or Bcl-2 inhibitor ABT737 showed synergistic suppressive effects. Our finding suggested that CAPE treatment induced cell cycle arrest and growth inhibition in CRPC cells via regulation of Skp2, p53, p21Cip1, and p27Kip1. PMID:25788262

  2. Caffeic acid phenethyl ester induced cell cycle arrest and growth inhibition in androgen-independent prostate cancer cells via regulation of Skp2, p53, p21Cip1 and p27Kip1.

    PubMed

    Lin, Hui-Ping; Lin, Ching-Yu; Huo, Chieh; Hsiao, Ping-Hsuan; Su, Liang-Cheng; Jiang, Shih Sheng; Chan, Tzu-Min; Chang, Chung-Ho; Chen, Li-Tzong; Kung, Hsing-Jien; Wang, Horng-Dar; Chuu, Chih-Pin

    2015-03-30

    Prostate cancer (PCa) patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant prostate cancer (CRPC) within 1-3 years. Treatment with caffeic acid phenethyl ester (CAPE) suppressed cell survival and proliferation via induction of G1 or G2/M cell cycle arrest in LNCaP 104-R1, DU-145, 22Rv1, and C4-2 CRPC cells. CAPE treatment also inhibited soft agar colony formation and retarded nude mice xenograft growth of LNCaP 104-R1 cells. We identified that CAPE treatment significantly reduced protein abundance of Skp2, Cdk2, Cdk4, Cdk7, Rb, phospho-Rb S807/811, cyclin A, cyclin D1, cyclin H, E2F1, c-Myc, SGK, phospho-p70S6kinase T421/S424, phospho-mTOR Ser2481, phospho-GSK3? Ser21, but induced p21Cip1, p27Kip1, ATF4, cyclin E, p53, TRIB3, phospho-p53 (Ser6, Ser33, Ser46, Ser392), phospho-p38 MAPK Thr180/Tyr182, Chk1, Chk2, phospho-ATM S1981, phospho-ATR S428, and phospho-p90RSK Ser380. CAPE treatment decreased Skp2 and Akt1 protein expression in LNCaP 104-R1 tumors as compared to control group. Overexpression of Skp2, or siRNA knockdown of p21Cip1, p27Kip1, or p53 blocked suppressive effect of CAPE treatment. Co-treatment of CAPE with PI3K inhibitor LY294002 or Bcl-2 inhibitor ABT737 showed synergistic suppressive effects. Our finding suggested that CAPE treatment induced cell cycle arrest and growth inhibition in CRPC cells via regulation of Skp2, p53, p21Cip1, and p27Kip1. PMID:25788262

  3. Further Studies of the Ability of Xyloglucan Oligosaccharides to Inhibit Auxin-Stimulated Growth 1

    PubMed Central

    Augur, Christopher; Yu, Lu; Sakai, Keiichiro; Ogawa, Tomoya; Sinaÿ, Pierre; Darvill, Alan G.; Albersheim, Peter

    1992-01-01

    The structural features required for xyloglucan oligosaccharides to inhibit 2,4-dichlorophenoxyacetic acid-stimulated elongation of pea stem segments have been investigated. A nonasaccharide (XG9) containing one fucosyl-galactosyl side chain and an undecasaccharide (XG11) containing two fucosyl-galactosyl side chains were purified from endo-?-1,4-glucanase-treated xyloglucan, which had been isolated from soluble extracellular polysaccharides of suspension-cultured sycamore (Acerpseudoplatanus) cells and tested in the pea stem bioassay. A novel octasaccharide (XG8?) was prepared by treatment of XG9 with a xyloglucan oligosaccharide-specific ?-xylosidase from pea seedlings. XG8? was characterized and tested for its ability to inhibit auxin-induced growth. All three oligosaccharides, at a concentration of 0.1 microgram per milliliter, inhibited 2,4-dichlorophenoxyacetic acid-stimulated growth of pea stem segments. XG11 inhibited the growth to a greater extent than did XG9. Chemically synthesized nona- and pentasaccharides (XG9, XG5) inhibited 2,4-dichlorophenoxyacetic acid-stimulated elongation of pea stems to the same extent as the same oligosaccharides isolated from xyloglucan. A chemically synthesized structurally related heptasaccharide that lacked a fucosyl-galactosyl side chain did not, unlike the identical heptasaccharide isolated from xyloglucan, significantly inhibit 2,4-dichlorophenoxyacetic acid-stimulated growth. PMID:16668847

  4. Trans fatty acids promote the growth of some Lactobacillus strains.

    PubMed

    Endo, Yasushi; Kamisada, Shusuke; Fujimoto, Kenshiro; Saito, Tadao

    2006-02-01

    Five Lactobacillus strains (2 L. gasseri, 2 L. plantarum and 1 L. reuteri) were cultured in modified MRS medium containing fatty acids (FAs) instead of Tween 80 for 24 h at 37 degrees C, to learn the effect of saturated and unsaturated FAs on the Lactobacillus growth. Free FAs included palmitic (16:0), palmitoleic (c9-16:1), stearic (18:0), oleic (c9-18:1), elaidic (t9-18:1), cis-vaccenic (c11-18:1), vaccenic (t11-18:1), linoleic (c9, c12-18:2), conjugated linoleic (c9, t11- and t10, c12-18:2), alpha-linolenic (c9, c12, c15-18:3), alpha-eleostearic (c9, t11, t13-18:3), eicosapentaenoic (20:5), and docosahexaenoic (22:6) acids. Among free FAs, oleic acid stimulated the growth of all Lactobacillus strains, whereas palmitoleic acid had almost no affect on the Lactobacillus growth. Saturated FAs such as stearic and palmitic acids inhibited or did not affect the Lactobacillus growth. Polyunsaturated FAs such as alpha-linolenic, eicosapentaenoic and docosahexaenoic acids strongly inhibited the Lactobacillus growth at 7.6 x 10(-4) m. Octadecenoic acids such as oleic, elaidic, cis-vaccenic and vaccenic acids remarkably promoted the growth of L. gasseri, regardless of the different double bond positions and configurations. When oleic or cis-vaccenic acid was incubated with L. gasseri, the FAs was transformed to cyclopropane FAs (methyleneoctadecanoic acids) after incorporation into the cells. On the other hand, trans FAs such as elaidic and vaccenic acids incorporated into the cells were not converted to another FAs. Conjugated linoleic and alpha-eleostearic acids having a trans double bond promoted the Lactobacillus growth. The growth of L. gasseri was also stimulated by trans-rich free FAs from hydrogenated canola and fish oils. These results showed that octadecenoic acid and trans FAs had strong promotion activities for the Lactobacillus growth due to their incorporation into membrane lipids. PMID:16598156

  5. Differential sensitivity of rice pathogens to growth inhibition by flavonoids

    Microsoft Academic Search

    Manchikanti Padmavati; Natarajan Sakthivel; K. V. Thara; Arjula R. Reddy

    1997-01-01

    Differential sensitivity of the major pathogens of rice, Xanthomonas oryzae pv. oryzae, Pyricularia oryzae and Rhizoctonia solani to inhibition by certain flavonoids was tested using paper disc\\/liquid culture and spore germination assays. Naringenin, the first intermediate of the flavonoid pathway, displayed growth inhibition of Xanthomonas strains and spore germination of P. oryzae. On the other hand, no such inhibition was

  6. Ligands for Peroxisome Proliferator-Activated Receptorgamma and Retinoic Acid Receptor Inhibit Growth and Induce Apoptosis of Human Breast Cancer Cells in vitro and in BNX Mice

    Microsoft Academic Search

    Elena Elstner; Carsten Muller; Kozo Koshizuka; Elizabeth A. Williamson; Dorothy Park; Hiroya Asou; Peter Shintaku; Jonathan W. Said; David Heber; H. Phillip Koeffler

    1998-01-01

    Induction of differentiation and apoptosis in cancer cells through ligands of nuclear hormone receptors (NHRs) is a novel and promising approach to cancer therapy. All-trans-retinoic acid (ATRA), an RA receptor-specific NHR ligand, is now used for selective cancers. The NHR, peroxisome proliferator-activated receptor gamma (PPARgamma ) is expressed in breast cancer cells. Activation of PPARgamma through a synthetic ligand, troglitazone

  7. Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression.

    PubMed

    Chen, Nian-Hong; Liu, Jian-Wen; Zhong, Jian-Jiang

    2010-01-01

    The traditional Chinese medicinal mushroom, Ganoderma lucidum, has been used in Asia for several thousand years for the prevention and treatment of a variety of diseases, including cancer. In previous work, we purified ganoderic acid T (GA-T) from G. lucidum [28]. In the present study, we investigate the functions of GA-T in terms of its effects on invasion in vitro and metastasis in vivo. A trypan blue dye exclusion assay indicates that GA-T inhibits proliferation of HCT-116 cells, a human colon carcinoma cell line. Cell aggregation and adhesion assays show that GA-T promotes homotypic aggregation and simultaneously inhibits the adhesion of HCT-116 cells to the extracellular matrix (ECM) in a dose-dependent manner.Wound healing assays indicate that GA-T also inhibits the migration of HCT-116 cells in a dose-dependent manner, and it suppresses the migration of 95-D cells, a highly metastatic human lung tumor cell line, in a dose- and time-dependent manner. In addition, GA-T inhibits the nuclear translocation of nuclear factor-kappaB (NF-kappaB) and the degradation of inhibitor of kappaB-alpha (IkappaBalpha), which leads to down-regulated expression of matrix metalloproteinase-9 (MMP-9), inducible nitric oxide synthase (iNOS), and urokinase-type plasminogen activator (uPA). Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrate that GA-T suppresses tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo. Taken together, these results demonstrate that GA-T effectively inhibits cancer cell invasion in vitro and metastasis in vivo, and thus it may act as a potential drug for treating cancer. PMID:20360625

  8. Gambogic acid inhibits angiogenesis through inhibiting PHD2-VHL-HIF-1? pathway.

    PubMed

    Lu, Na; Hui, Hui; Yang, Hao; Zhao, Kai; Chen, Yan; You, Qi-Dong; Guo, Qing-Long

    2013-05-13

    Our previous studies revealed that gambogic acid (GA), the major active ingredient of gamboge, possessed antiangiogenic activities. In this study, we further explored the mechanism of inhibition effects of GA in tumor angiogenesis. The results of luciferase, RT-PCR, and ELISA assays indicated that GA significantly decreased transcription activation, mRNA expression, and secretion of VEGF in hypoxia. We detected that GA had no effect on mRNA level of HIF-1? which targets VEGF gene, but the increase of HIF-1? protein expression in hypoxia was repressed by GA, which can be reversed by proteasomal inhibitor MG132 and siRNA of VHL. But GA exhibited no effect on expression of VHL both in normoxia and hypoxia. HIF prolyl hydroxylases (PHD enzymes) act as oxygen sensors regulating HIF, and hence angiogenesis. Our results showed that GA potentially enhanced level of PHD2, the most important HIF hydroxylase, and showed no effect on PHD1 and PHD3. Transient transfection of siRNA of PHD2 could eliminate GA-induced VEGF secretion increase. Growth of HepG2 xenografts in BALB/cA nude mice was inhibited by GA and angiogenesis was repressed significantly in tumor xenografts by immunohistochemical staining of CD-31, a vascular endothelial marker, accompanied with decrease of HIF-1? and increase of PHD2 expression in tissue extracts. This work provides the demonstration that GA shows anti-angiogenic effects via inhibiting PHD2-VHL-HIF-1? pathway. PMID:23501055

  9. Inhibition of Aluminum Oxyhydroxide Precipitation with Citric Acid

    E-print Network

    Aksay, Ilhan A.

    Inhibition of Aluminum Oxyhydroxide Precipitation with Citric Acid Daniel M. Dabbs, Usha, Washington 99352 Received March 29, 2005. In Final Form: July 29, 2005 Citric acid has been shown to act/mol) hydroxide-to-aluminum ratios. Conversely, citric acid also colloidally stabilizes particles in aqueous

  10. Inhibition against growth of glioblastoma multiforme in vitro using etoposide-loaded solid lipid nanoparticles with p-aminophenyl-?-D-manno-pyranoside and folic acid.

    PubMed

    Kuo, Yung-Chih; Lee, Chia-Hao

    2015-05-01

    Solid lipid nanoparticles (SLNs) grafted with p-aminophenyl-?-D-manno-pyranoside (APMP) and folic acid (FA) (APMP-FA-SLNs) were applied to encapsulate 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-?-D-glucopyranoside) (etoposide) (ETP) for promoting the antiproliferation of malignant glioblastoma multiforme. ETP-loaded APMP-FA-SLNs (APMP-FA-ETP-SLNs) were used to penetrate the blood-brain barrier (BBB) and retard the propagation of U87MG cells. An incorporation of APMP and FA increased the particle size, the cytotoxicity to U87MG cells, and the permeability coefficient for propidium iodide and ETP across the BBB. In addition, an increase in the APMP and FA concentration reduced the zeta potential, the grafting efficiency of APMP and FA, the dissolution rate of ETP, and the transendothelial electrical resistance. Immunochemical staining images evidenced that APMP-FA-ETP-SLNs could infiltrate the BBB via glucose transporter 1 and recognize U87MG cells via folate receptor. APMP-FA-ETP-SLNs can be an effective pharmacotherapeutic formulation in targeting delivery to the brain and in inhibitory efficacy against tumorous cells for cancer therapy. PMID:25694089

  11. Pomegranate Juice Metabolites, Ellagic Acid and Urolithin A, Synergistically Inhibit Androgen-Independent Prostate Cancer Cell Growth via Distinct Effects on Cell Cycle Control and Apoptosis

    PubMed Central

    Vicinanza, Roberto; Henning, Susanne M.; Heber, David

    2013-01-01

    Ellagitannins (ETs) from pomegranate juice (PJ) are bioactive polyphenols with chemopreventive potential against prostate cancer (PCa). ETs are not absorbed intact but are partially hydrolyzed in the gut to ellagic acid (EA). Colonic microflora can convert EA to urolithin A (UA), and EA and UA enter the circulation after PJ consumption. Here, we studied the effects of EA and UA on cell proliferation, cell cycle, and apoptosis in DU-145 and PC-3 androgen-independent PCa cells and whether combinations of EA and UA affected cell proliferation. EA demonstrated greater dose-dependent antiproliferative effects in both cell lines compared to UA. EA induced cell cycle arrest in S phase associated with decreased cyclin B1 and cyclin D1 levels. UA induced a G2/M arrest and increased cyclin B1 and cdc2 phosphorylation at tyrosine-15, suggesting inactivation of the cyclin B1/cdc2 kinase complex. EA induced apoptosis in both cell lines, while UA had a less pronounced proapoptotic effect only in DU-145. Cotreatment with low concentrations of EA and UA dramatically decreased cell proliferation, exhibiting synergism in PC-3 cells evaluated by isobolographic analysis and combination index. These data provide information on pomegranate metabolites for the prevention of PCa recurrence, supporting the role of gut flora-derived metabolites for cancer prevention. PMID:23710216

  12. Bee venom inhibits growth of human cervical tumors in mice.

    PubMed

    Lee, Hye Lim; Park, Sang Ho; Kim, Tae Myoung; Jung, Yu Yeon; Park, Mi Hee; Oh, Sang Hyun; Yun, Hye Seok; Jun, Hyung Ok; Yoo, Hwan Soo; Han, Sang-Bae; Lee, Ung Soo; Yoon, Joo Hee; Song, Min Jong; Hong, Jin Tae

    2015-03-30

    We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-?B) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1-5 ?g/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-?B activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-?B inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-?B pathway. PMID:25730901

  13. Bee venom inhibits growth of human cervical tumors in mice

    PubMed Central

    Kim, Tae Myoung; Jung, Yu Yeon; Park, Mi Hee; Oh, Sang Hyun; Yun, Hye Seok; Jun, Hyung Ok; Yoo, Hwan Soo; Han, Sang-Bae; Lee, Ung Soo; Yoon, Joo Hee; Song, Min Jong; Hong, Jin Tae

    2015-01-01

    We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-?B) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1–5 ?g/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-?B activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-?B inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-?B pathway. PMID:25730901

  14. Green tea inhibits Helicobacter growth in vivo and in vitro

    PubMed Central

    Stoicov, Calin; Saffari, Reza; Houghton, JeanMarie

    2009-01-01

    Helicobacter infection, one of the most common bacterial infections in man worldwide, is a type 1 carcinogen and the most important risk factor for gastric cancer. Helicobacter pylori bacterial factors, components of the host genetics and immune response, dietary cofactors and decreased acid secretion resulting in bacterial overgrowth are all considered important factors for induction of gastric cancer. Components found in green tea have been shown to inhibit bacterial growth, including the growth of Helicobacter spp. In this study, we assessed the bactericidal and/or bacteriostatic effect of green tea against Helicobacter felis and H. pylori in vitro and evaluated the effects of green tea on the development of Helicobacter-induced gastritis in an animal model. Our data clearly demonstrate profound growth effects of green tea against Helicobacter and, importantly, demonstrate that green tea consumption can prevent gastric mucosal inflammation if ingested prior to exposure to Helicobacter infection. Research in the area of natural food compounds and their effects on various disease states has gained increased acceptance in the past several years. Components within natural remedies such as green tea could be further used for prevention and treatment of Helicobacter-induced gastritis in humans. PMID:19157800

  15. Novel lactic acid bacteria inhibiting Paenibacillus larvae in honey bee larvae

    Microsoft Academic Search

    Eva Forsgren; Tobias C. Olofsson; Alejandra Váasquez; Ingemar Fries

    2010-01-01

    We evaluated the antagonistic effects of newly identified lactic acid bacteria (LAB) in the genera Lactobacillus and Bifidobacterium, originating from the honey stomach, on the honey bee pathogen, Paenibacillus larvae. We used inhibition assays on agar plates and honey bee larval bioassays to investigate the effects of honey bee LAB on P. larvae growth in vitro and on AFB infection

  16. Inhibition of growth of Zymomonas mobilis by model compounds found in lignocellulosic hydrolysates

    PubMed Central

    2013-01-01

    Background During the pretreatment of biomass feedstocks and subsequent conditioning prior to saccharification, many toxic compounds are produced or introduced which inhibit microbial growth and in many cases, production of ethanol. An understanding of the toxic effects of compounds found in hydrolysate is critical to improving sugar utilization and ethanol yields in the fermentation process. In this study, we established a useful tool for surveying hydrolysate toxicity by measuring growth rates in the presence of toxic compounds, and examined the effects of selected model inhibitors of aldehydes, organic and inorganic acids (along with various cations), and alcohols on growth of Zymomonas mobilis 8b (a ZM4 derivative) using glucose or xylose as the carbon source. Results Toxicity strongly correlated to hydrophobicity in Z. mobilis, which has been observed in Escherichia coli and Saccharomyces cerevisiae for aldehydes and with some exceptions, organic acids. We observed Z. mobilis 8b to be more tolerant to organic acids than previously reported, although the carbon source and growth conditions play a role in tolerance. Growth in xylose was profoundly inhibited by monocarboxylic organic acids compared to growth in glucose, whereas dicarboxylic acids demonstrated little or no effects on growth rate in either substrate. Furthermore, cations can be ranked in order of their toxicity, Ca++ >?>?Na+?>?NH4+?>?K+. HMF (5-hydroxymethylfurfural), furfural and acetate, which were observed to contribute to inhibition of Z. mobilis growth in dilute acid pretreated corn stover hydrolysate, do not interact in a synergistic manner in combination. We provide further evidence that Z. mobilis 8b is capable of converting the aldehydes furfural, vanillin, 4-hydroxybenzaldehyde and to some extent syringaldehyde to their alcohol forms (furfuryl, vanillyl, 4-hydroxybenzyl and syringyl alcohol) during fermentation. Conclusions Several key findings in this report provide a mechanism for predicting toxic contributions of inhibitory components of hydrolysate and provide guidance for potential process development, along with potential future strain improvement and tolerance strategies. PMID:23837621

  17. Protective effect of antioxidants against para-nonylphenol-induced inhibition of cell growth in Saccharomyces cerevisiae.

    PubMed

    Okai, Y; Higashi-Okai, K; Machida, K; Nakamura, H; Nakayama, K; Fujita, K; Tanaka, T; Otani, S; Taniguchi, M

    2000-04-01

    The cell growth-modulating activity of an endocrine disruptor, p-nonylphenol (NP), was estimated using the yeast Saccharomyces cerevisiae as a simple model of eukaryotic cells. NP caused a dose-dependent suppressive effect on cell growth of S. cerevisiae at 10, 25 and 50 microM. The NP-induced cell growth inhibition was restored when concomitantly lipophilic antioxidants such as alpha-tocopherol and beta-carotene were supplied, but not the hydrophilic antioxidants ascorbic acid or (-)epigallocatechin gallate (EGCG). The cellular oxygen consumption of S. cerevisiae was also inhibited in a dose-dependent fashion by the extracellular addition of NP, and pretreatment with alpha-tocopherol and beta-carotene suppressed NP-induced inhibition of cellular oxygen consumption, but ascorbic acid and EGCG were not effective. Furthermore, NP caused a marked generation of radical oxygen species (ROS) in S. cerevisiae, which was suppressed by treatment with alpha-tocopherol and beta-carotene, but not with ascorbic acid and EGCG. However, NP did not show a significant inhibitory effect on cell growth and survival of mitochondria-deficient petite mutant cells and they showed a relatively weak ROS-generating activity compared with parent yeast cells. These results suggest that NP-induced inhibition of cell growth and oxygen consumption in S. cerevisiae might be possibly associated with ROS generation in yeast mitochondria. The significance of this finding is discussed from the viewpoint of NP-induced oxidative stress against eukaryotic cells. PMID:10731608

  18. Inhibition of fucosyltransferase VII by gallic acid and its derivatives

    Microsoft Academic Search

    Xiaoda Niu; Xuedong Fan; Jing Sun; Pauline Ting; Satwant Narula; Daniel Lundell

    2004-01-01

    Gallic acid (GA) and several gallate derivatives were identified as inhibitors of fucosyltransferase VII (FucT VII). The inhibition by GA and (?)-epigallocatechin gallate (EGCG) is time-dependent and irreversible. GA and EGCG showed inhibition with IC50 of 60 and 700nM, respectively, after pre-incubation with FucT VII in the presence of MnCl2. Absence of MnCl2 results in significantly weaker inhibition. Complexation of

  19. Spray Application Parameters That Influence the Growth Inhibiting Effects of Trinexapac-Ethyl

    Microsoft Academic Search

    Matthew James Fagerness; Donald Penner

    1998-01-01

    identifies a broad range of effective spray carrier vol- umes (187-1683 L ha2 1 ), achievement of rainfastness Trinexapac-ethyl (4-(cyclopropyl-a-hydroxy-methylene)-3,5-diox- within 1 h after application, and no need for an adjuvant ocyclohexanecarboxylic acid ethyl ester) is a foliar absorbed, cyclohex- to enhance efficacy. There is little evidence available to anedione turfgrass growth regulator that can inhibit shoot growth in numerous

  20. D-amino acids indirectly inhibit biofilm formation in Bacillus subtilis by interfering with protein synthesis.

    PubMed

    Leiman, Sara A; May, Janine M; Lebar, Matthew D; Kahne, Daniel; Kolter, Roberto; Losick, Richard

    2013-12-01

    The soil bacterium Bacillus subtilis forms biofilms on surfaces and at air-liquid interfaces. It was previously reported that these biofilms disassemble late in their life cycle and that conditioned medium from late-stage biofilms inhibits biofilm formation. Such medium contained a mixture of D-leucine, D-methionine, D-tryptophan, and D-tyrosine and was reported to inhibit biofilm formation via the incorporation of these D-amino acids into the cell wall. Here, we show that L-amino acids were able to specifically reverse the inhibitory effects of their cognate D-amino acids. We also show that D-amino acids inhibited growth and the expression of biofilm matrix genes at concentrations that inhibit biofilm formation. Finally, we report that the strain routinely used to study biofilm formation has a mutation in the gene (dtd) encoding D-tyrosyl-tRNA deacylase, an enzyme that prevents the misincorporation of D-amino acids into protein in B. subtilis. When we repaired the dtd gene, B. subtilis became resistant to the biofilm-inhibitory effects of D-amino acids without losing the ability to incorporate at least one noncanonical D-amino acid, D-tryptophan, into the peptidoglycan peptide side chain. We conclude that the susceptibility of B. subtilis to the biofilm-inhibitory effects of D-amino acids is largely, if not entirely, due to their toxic effects on protein synthesis. PMID:24097941

  1. Novel therapeutic approach: organic arsenical (melarsoprol) alone or with all-trans -retinoic acid markedly inhibit growth of human breast and prostate cancer cells in vitro and in vivo

    PubMed Central

    Koshiuka, K; Elstner, E; Williamson, E; Said, J W; Tada, Y; Koeffler, H P

    2000-01-01

    The organic arsenical known as melarsoprol (Mel-B) is used to treat African trypanosomiasis. Recently, another arsenical, As2O3was shown to be effective in treatment of acute promyelocytic leukaemia. We have investigated the anti-tumour activities of Mel-B either with or without all-trans -retinoic acid (ATRA) using the MCF-7 human breast cancer cells, as well as the PC-3 and DU 145 human prostate cancer cells both in vitro and in vivo. The antiproliferative effects of Mel-B and/or ATRA against breast and prostate cancer were tested in vitro using clonogenic assays and in vivo in triple immunodeficient mice. Furthermore, the mechanism of action of these compounds was studied by examining the cell cycle, levels of bcl-2, apoptosis and antiproliferative potency using a pulse-exposure assay. Clonogenic assays showed that the cancer cell lines were sensitive to the inhibitory effect of Mel-B (effective dose that inhibited 50% clonal growth [ED50]: 7 × 10?9M for MCF-7, 2 × 10?7M for PC-3, 3 × 10?7M for DU145 cells. Remarkably, the combination of Mel-B and ATRA had an enhanced antiproliferative activity against all three cancer cell lines. Furthermore, the combination of Mel-B and ATRA induced a high level of apoptosis in all three cell lines. Treatment of PC-3 and MCF-7 tumours growing in triple immunodeficient mice with Mel-B and ATRA either alone or in combination markedly retarded tumour size and weight of the tumours without major side-effects. In conclusion, our results suggest that either Mel-B alone or with ATRA may be a useful, novel therapy for breast and prostate cancers. © 2000 Cancer Research Campaign PMID:10646904

  2. AUXIN-INDUCED SPROUT GROWTH INHIBITION: ROLE OF ENDOGENOUS ETHYLENE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of endogenous ethylene in auxin-mediated tuber sprout growth inhibition was determined in potato (Solanum tuberosum L. cv. Russet Burbank) minitubers. Treatment of tubers with biologically active auxins resulted in transient, dose-dependent increase in ethylene production and inhibition of...

  3. Inhibition and stimulation of yeast growth by acetaldehyde

    Microsoft Academic Search

    G. A. Stanley; N. G. Douglas; E. J. Every; T. Tzanatos; N. B. Pamment

    1993-01-01

    Acetaldehyde at above about 0.3 g\\/l inhibited yeast growth, suggesting that it may contribute to product inhibition in alcohol fermentations when present at high concentrations intracellularly. The toxic effects of acetaldehyde and ethanol were not mutually reinforcing, acetaldehyde appearing to alleviate slightly the effects of ethanol. In support of this, low concentrations of acetaldehyde greatly reduced the lag phase in

  4. INHIBITION OF LEUKOCYTE LOCOMOTION BY HYALURONIC ACID

    Microsoft Academic Search

    J. V. FORRESTER; P. C. WILKINSONf

    1981-01-01

    SUMMARY The effect of hyaluronate on neutrophil motility in vitro was studied by the micropore filter technique and by direct visual analysis of the locomotion of neutrophils on glass. Both directed and random locomotion of neutrophils were inhibited by physiological concentrations (0-5-6-0 mgml'^o f hyaluronate in a dose-and molecular weight-dependent manner. Inhibition of cell movement was more pronounced for high

  5. Saturated Fatty Acid Activates but Polyunsaturated Fatty Acid Inhibits Toll-like Receptor 2 Dimerized with

    E-print Network

    Lee, Won-Ha

    Saturated Fatty Acid Activates but Polyunsaturated Fatty Acid Inhibits Toll-like Receptor 2 saturated fatty acids in their molecules. Previously, we reported that TLR4 ac- tivation is reciprocally modulated by saturated and polyunsaturated fatty acids in macrophages. However, it is not known whether

  6. Effect of 2-alkynoic acids on in vitro growth of bacterial and mammalian cells.

    PubMed Central

    Konthikamee, W; Gilbertson, J R; Langkamp, H; Gershon, H

    1982-01-01

    3-Decynoyl-N-acetylcystamine is known to inhibit the in vitro growth of Escherichia coli but not of yeasts or mammalian cells. Neither the free acid nor the 2 positional isomer is active (L. R. Kass, J. Biol. Chem. 243:3223-3228, 1968). Other studies have shown that 2-hexadecynoic acid is fungitoxic whereas most of the shorter chain isomers are inactive (H. Gershon and L. Shanks, Can J. Microbiol. 24:591-597, 1978). Since these studies suggested that positional or chain length isomers of the acetylenic acids may selectively inhibit the growth of microorganisms, the effect of the alkynoic acids on the in vitro growth of gram-positive and gram-negative bacteria was evaluated. 2-Hexadecynoic acid was found to be the most active species. This acid was bacteriostatic for all gram-positive bacteria tested. The acid was readily taken up by the treated cells and incorporated into the phospholipid fraction. When added to the culture medium, 2-hexadecynoic acid inhibited the growth of HeLa cells, but when mixed with an equivalent amount of palmitic acid, growth inhibition was not observed. PMID:7181490

  7. Growth inhibition of human gastrointestinal cancer cells by cyclosporin A.

    PubMed

    Piontek, M; Porschen, R

    1994-01-01

    We have studied the ability of cyclosporin A (CsA) to inhibit the growth of human AGS gastric and HT29 colon carcinoma cells in vitro. Using continuous drug exposure in growth assays of cultured tumour cells we found that CsA produced a dose-dependent growth inhibition in gastric and colon cancer cells with a half-maximal effect at 5 microM and 6 microM CsA respectively. The growth inhibition of CsA was reversible in AGS cells, when the tumour cells were incubated in normal growth medium following CsA treatment. Trypan blue dye exclusion in AGS cells indicated a cytostatic rather than a cytotoxic effect in the concentration range used. Coincubation of CsA-treated cells with 10-400 U/ml interleukin-2 (IL-2) could not abrogate this growth inhibition, suggesting an IL-2 independent mechanism of action. Flow-cytometric analysis did not reveal a phase arrest of the gastric cancer cells within the cell cycle. We conclude from our experiments that CsA cytostatically and reversibly inhibits the growth of human gastric cancer cells in a dose-dependent manner. In contrast to its mechanism of action in lymphocytes, this direct antiproliferative effect of CsA seems not to be mediated by an IL-2-dependent pathway or a cell-cycle-phase arrest of the tumour cells. PMID:7798292

  8. Characterization of unsaturated fatty acid sustained-release microspheres for long-term algal inhibition.

    PubMed

    Ni, Lixiao; Jie, Xiaoting; Wang, Peifang; Li, Shiyin; Hu, Shuzhen; Li, Yiping; Li, Yong; Acharya, Kumud

    2015-02-01

    The unsaturated fatty acid (linoleic acid) sustained-release microspheres were prepared with linoleic acid (LA) using alginate-chitosan microcapsule technology. These LA sustained-release microspheres had a high encapsulation efficiency (up to 62%) tested by high performance liquid chromatography with a photo diode array. The dry microspheres were characterized by a scanning electron microscope, X-ray diffraction measurement, dynamic thermogravimetric analysis and Fourier transform infrared spectral analysis. The results of characterization showed that the microspheres had good thermal stability (decomposition temperature of 236°C), stable and temperature independent release properties (release time of more than 40 d). Compared to direct dosing of LA, LA sustained-released microspheres could inhibit Microcystis aeruginosa growth to the non-growth state. The results of this study suggested that the LA sustained-release microspheres may be a potential candidate for algal inhibition. PMID:25201788

  9. Reexamination of the Acid Growth Theory of Auxin Action 1

    PubMed Central

    Lüthen, Hartwig; Bigdon, Michael; Böttger, Michael

    1990-01-01

    Some crucial arguments against the acid growth theory of auxin action (U Kutschera, P Schopfer [1985] Planta 163: 483-493) have been reinvestigated by simultaneous measurements of proton fluxes and growth of maize (Zea mays L.) coleoptiles. Special care was taken to obtain a mild, effective, and reproducible abrasion of the cuticle. Proton secretion rates were determined in a computer-controlled pH-stat. In some experiments, equilibrium pH was measured. Growth rates were determined simultaneously in the same vessel using a transducer-type auxanometer. It was found that (a) the timing of auxin and fusicoccin-induced (FC) proton secretion and growth matches well, (b) the equilibrum external pHs in the presence of IAA and FC are lower than previously recorded and below the so-called `threshold-pH,' (c) neutral or alkaline unbuffered solutions partially inhibit FC and IAA-induced growth in a similar manner, (d) the action of pH, FC, and IAA on growth are not additive. It is concluded that the acid-growth-theory correctly describes incidents taking place in the early phases of auxin-induced growth. Images Figure 1 PMID:16667603

  10. Inhibition of water absorption by ricinoleic acid

    Microsoft Academic Search

    Thomas R. Gadacz; Timothy S. Gaginella; Sidney F. Phillips

    1976-01-01

    In three dogs, each with a jejunal and an ileal Thiry-Vella loop, the isolated segments were perfused with isotonic electrolyte solutions (control) for 90 min. One loop was then perfused with 5 mM ricinoleic acid for an additional 90 min, while the other loop was perfused with the control solution. Loops perfused with ricinoleci acid all showed reduced fluid absorption.

  11. Root growth inhibition by NH4 in Arabidopsis is mediated

    E-print Network

    Kronzucker, Herbert J.

    Root growth inhibition by NH4 + in Arabidopsis is mediated by the root tip and is linked to NH4 Military Trail, Toronto, Ontario, M1C 1A4, Canada ABSTRACT Root growth in higher plants is sensitive to excess ammo- nium (NH4 + ). Our study shows that contact of NH4 + with the primary root tip is both

  12. Acidic peptide and polyribonucleotide crystal growth inhibitors in human urine.

    PubMed

    Ito, H; Coe, F L

    1977-11-01

    Urine contains nondialyzable inhibitors of calcium oxalate crystal growth. We have pursued the hypothesis that these inhibitors may, in part, be acidic peptides and polyribonucleotide fragments. Homopolyribonucleotides and RNA inhibit calcium oxalate crystal growth at 5 x 10(-6) M of constituent ribonucleotide, whereas the monomer nucleotides are inactive at 10(-4) M. Poly-L-aspartic or glutamic acid are also inhibitory at 5 X 10(-6) M of amino acid, whereas the monomeric amino acids are inert. Gastric pepsin, a naturally occurring acidic peptide, is inhibitory. Incubation with nonspecific protease reduced the inhibitory effectiveness of normal human urine consistently and significantly, a fact compatible with an important contribution of peptides. A variable additional reduction was produced by subsequent treatment with ribonuclease, suggesting only a small role for polyribonucleotide. Sequential ion exchange and gel filtration chromatography and preparative disc gel electrophoresis yielded inhibitory material enriched with peptides that were strongly acidic and high in proline. Peptides and ribonucleotides seem to contribute to urinary nondialyzable crystal growth inhibitory activity. PMID:920814

  13. Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by orlistat

    SciTech Connect

    Pemble,C.; Johnson, L.; Kridel, S.; Lowther, W.

    2007-01-01

    Human fatty acid synthase (FAS) is uniquely expressed at high levels in many tumor types. Pharmacological inhibition of FAS therefore represents an important therapeutic opportunity. The drug Orlistat, which has been approved by the US Food and Drug Administration, inhibits FAS, induces tumor cell-specific apoptosis and inhibits the growth of prostate tumor xenografts. We determined the 2.3-{angstrom}-resolution crystal structure of the thioesterase domain of FAS inhibited by Orlistat. Orlistat was captured in the active sites of two thioesterase molecules as a stable acyl-enzyme intermediate and as the hydrolyzed product. The details of these interactions reveal the molecular basis for inhibition and suggest a mechanism for acyl-chain length discrimination during the FAS catalytic cycle. Our findings provide a foundation for the development of new cancer drugs that target FAS.

  14. DASATINIB INHIBITS THE GROWTH OF MOLECULARLY HETEROGENEOUS MYELOID LEUKEMIAS

    PubMed Central

    Guerrouahen, Bella S.; Futami, Muneyoshi; Vaklavas, Christos; Kanerva, Jukka; Whichard, Zakary L.; Nwawka, Kenechi; Blanchard, Elisabeth G.; Lee, Francis Y.; Robinson, Lisa J.; Arceci, Robert; Kornblau, Steven M.; Wieder, Eric; Cayre, Yvon E.; Corey, Seth J.

    2010-01-01

    Purpose Dasatinib is a dual Src/Abl inhibitor, recently approved for Bcr-Abl+ leukemias with resistance or intolerance to prior therapy. Because Src kinases contribute to multiple blood cell functions by triggering a variety of signaling pathways, we hypothesized that their molecular targeting might lead to growth inhibition in acute myeloid leukemia (AML). Experimental Design We studied growth factor-dependent and independent leukemic cell lines, including three cell lines expressing mutants of receptor tyrosine kinases (Flt3 or c-Kit) as well as primary AML blasts for responsiveness to dasatinib. Results Dasatinib resulted in the inhibition of Src family kinases in all cell lines and blast cells at ~10?9 M. It also inhibited mutant Flt3 or Kit tyrosine phosphorylation at ~10?6 M. Mo7e cells expressing the activating mutation (codon 816) of c-Kit were most sensitive to growth inhibition with a GI50 5×10?9 M. Primary AML blast cells exhibited growth inhibition < 10?6 M. Cell lines which showed growth inhibition at ~10?6 M demonstrated a G1 cell cycle arrest and correlated with accumulation of p21 and p27 protein. Addition of rapamycin or cytotoxic agents enhanced the growth inhibition. Dasatinib also caused the apoptosis of Mo7e cells expressing oncogenic Kit. Conclusions While all of the precise targets for dasatinib are not known, this multi-kinase inhibitor causes either growth arrest or apoptosis in molecularly heterogeneous AML. Addition of cytotoxic or targeted agents can enhance its effects. PMID:20145167

  15. RGD-Tachyplesin Inhibits Tumor Growth1

    Microsoft Academic Search

    Yixin Chen; Xueming Xu; Shuigen Hong; Jinguo Chen; Ningfei Liu; Charles B. Underhill; Karen Creswell; Lurong Zhang

    2001-01-01

    Tachyplesin is an antimicrobial peptide present in leukocytes of the horseshoe crab (Tachypleus tridentatus). In this study, a synthetic tachyplesin conjugated to the integrin homing domain RGD was tested for antitumor activity. The in vitro results showed that RGD-tachyplesin inhibited the proliferation of both cultured tumor and endothelial cells and reduced the colony formation of TSU prostate cancer cells. Staining

  16. Progesterone Inhibits Folic Acid Transport in Human Trophoblasts

    Microsoft Academic Search

    Elisa Keating; Pedro Gonçalves; Clara Lemos; Fernanda Costa; Isabel Campos; Sylvia B. Smith; Christy C. Bridges; Fátima Martel

    2007-01-01

    The aim of this work was to test the putative involvement of members of the ABC superfamily of transporters on folic acid\\u000a (FA) cellular homeostasis in the human placenta. [3H]FA uptake and efflux in BeWo cells were unaffected or hardly affected by multidrug resistance 1 (MDR1) inhibition (with\\u000a verapamil), multidrug resistance protein (MRP) inhibition (with probenecid) or breast cancer resistance

  17. Boswellic acid inhibits expression of acid sphingomyelinase in intestinal cells

    Microsoft Academic Search

    Yao Zhang; Rui-Dong Duan

    2009-01-01

    BACKGROUND: Boswellic acid is a type of triterpenoids with antiinflammatory and antiproliferative properties. Sphingomyelin metabolism generates multiple lipid signals affecting cell proliferation, inflammation, and apoptosis. Upregulation of acid sphingomyelinase (SMase) has been found in several inflammation-related diseases such as inflammatory bowel diseases, atherosclerosis, and diabetes. METHODS: The present study is to examine the effect of 3-acetyl-11-keto-?-boswellic acids (AKBA), a potent

  18. Lactobacillus by-products inhibit the growth and virulence of uropathogenic Escherichia coli.

    PubMed

    Cadieux, P A; Burton, J; Devillard, E; Reid, G

    2009-12-01

    Uropathogenic strains of Escherichia coli (UPEC) can colonize the vagina and cause infections within the entire urogenital tract, including those associated with urinary tract devices. Lactobacilli typically dominate the vaginal microbiota in healthy women, and studies have shown that they can inhibit UPEC growth and vaginal colonization. However, little is known regarding the mechanisms behind these effects. Using a luciferase-based reporter construct, gradients of lactic acid, hydrogen peroxide and spent culture supernatants (SCS) from urogenital probiotic strains Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 were examined for their effects on growth and virulence factor expression in UPEC isolate C1212. In a dose- and pH- dependent manner, lactic acid, hydrogen peroxide and Lactobacillus SCS all strongly inhibited UPEC C1212 growth and increased the promoter activity of outer membrane proteins (OMPs) A and X, two porins normally upregulated in response to UPEC membrane stress. Lactic acid and the culture supernatants also downregulated the promoter activity of the major subunits of type 1 and P fimbriae, critical adherence factors within the urogenital tract. Our findings indicate that compounds secreted by lactobacilli likely protect the urogenital tract from UPEC colonization and infection by inhibiting growth, inducing stress and downregulating proteins critical for host attachment. PMID:20224146

  19. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    SciTech Connect

    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)] [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)] [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)] [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan)] [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)] [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  20. MFR PAPER 1339 Phosphonoacetic Acid Inhibition of

    E-print Network

    - ing in malignancy (Biggs et al., 1972). Although several herpesviruses are capable of these multiple. The herpesviruses are no exception. Recently, however, a chemical derivative of the simple molecule acetic acid has to determine if CCY would show similar sensitivity to PAA. Increasing concentrations of PAA were prepared

  1. Inhibition of prostatic cancer growth by ginsenoside Rh2.

    PubMed

    Zhang, Qingchuan; Hong, Bin; Wu, Songhua; Niu, Tianli

    2015-04-01

    Ginsenoside Rh2 (GRh2) has been reported to have therapeutic effects on some types of cancer, but its effect on prostatic cancer has not been extensively evaluated. Here, we show that GRh2 can substantially inhibit the growth of prostatic cancer in vivo and in vitro. Moreover, the inhibition of the tumor growth appeared to result from a combined inhibitory effect on tumor cell proliferation and tumor cell invasiveness. Further analyses suggest that GRh2 seemed to activate transforming growth factor ? (TGF?) receptor signaling in prostatic cancer cells, which subsequently inhibits cell proliferation and invasion through regulating cell-cycle controllers and (MMPs), respectively. Taken together, our data reveal an essential anti-prostatic cancer effect of GRh2 and demonstrate that this effect is through augment of TGF? receptor signaling in the prostatic cancer cells. GRh2 thus appears to be a promising therapy for prostatic cancer. PMID:25416441

  2. Growth of nitric acid hydrates on thin sulfuric acid films

    NASA Technical Reports Server (NTRS)

    Iraci, Laura T.; Middlebrook, Ann M.; Wilson, Margaret A.; Tolbert, Margaret A.

    1994-01-01

    Type I polar stratospheric clouds (PSCs) are thought to nucleate and grow on stratospheric sulfate aerosols (SSAs). To model this system, thin sulfuric acid films were exposed to water and nitric acid vapors (1-3 x 10(exp -4) Torr H2O and 1-2.5 x 10(exp -6) Torr HNO3) and subjected to cooling and heating cycles. Fourier Transform Infrared (FTIR) spectroscopy was used to probe the phase of the sulfuric acid and to identify the HNO3/H2O films that condensed. Nitric acid trihydrate (NAT) was observed to grow on crystalline sulfuric acid tetrahydrate (SAT) films. NAT also condensed in/on supercooled H2SO4 films without causing crystallization of the sulfuric acid. This growth is consistent with NAT nucleation from ternary solutions as the first step in PSC formation.

  3. Oligodendrocytes Arrest Neurite Growth by Contact Inhibition

    Microsoft Academic Search

    Christine Bandtlow; Thomas Zachleder; Martin E. Schwab

    1990-01-01

    We have used video time-lapse microscopy to analyze in vitro the interactions of growth cones of newborn rat dorsal root ganglion cells with dissociated young rat CNS glial cells present in the cultures at low density. To provide optimal conditions for neurite extension, cells were grown on laminin and in NGF-supplemented medium. Our initial observations showed that there are 2

  4. Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth

    PubMed Central

    Ahmad, Zulfiqar; Laughlin, Thomas F.; Kady, Ismail O.

    2015-01-01

    We examined the thymoquinone induced inhibition of purified F1 or membrane bound F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control cells demonstrates that ATP synthase is a molecular target for thymoquinone. This also links the beneficial dietary based antimicrobial and anticancer effects of thymoquinone to its inhibitory action on ATP synthase. PMID:25996607

  5. Tannic Acid Inhibits Staphylococcus aureus Surface Colonization in an IsaA-Dependent Manner

    PubMed Central

    Payne, David E.; Martin, Nicholas R.; Parzych, Katherine R.; Rickard, Alex H.; Underwood, Adam

    2013-01-01

    Staphylococcus aureus is a human commensal and pathogen that is capable of forming biofilms on a variety of host tissues and implanted medical devices. Biofilm-associated infections resist antimicrobial chemotherapy and attack from the host immune system, making these infections particularly difficult to treat. In order to gain insight into environmental conditions that influence S. aureus biofilm development, we screened a library of small molecules for the ability to inhibit S. aureus biofilm formation. This led to the finding that the polyphenolic compound tannic acid inhibits S. aureus biofilm formation in multiple biofilm models without inhibiting bacterial growth. We present evidence that tannic acid inhibits S. aureus biofilm formation via a mechanism dependent upon the putative transglycosylase IsaA. Tannic acid did not inhibit biofilm formation of an isaA mutant. Overexpression of wild-type IsaA inhibited biofilm formation, whereas overexpression of a catalytically dead IsaA had no effect. Tannin-containing drinks like tea have been found to reduce methicillin-resistant S. aureus nasal colonization. We found that black tea inhibited S. aureus biofilm development and that an isaA mutant resisted this inhibition. Antibiofilm activity was eliminated from tea when milk was added to precipitate the tannic acid. Finally, we developed a rodent model for S. aureus throat colonization and found that tea consumption reduced S. aureus throat colonization via an isaA-dependent mechanism. These findings provide insight into a molecular mechanism by which commonly consumed polyphenolic compounds, such as tannins, influence S. aureus surface colonization. PMID:23208606

  6. Provitamin B5 (Pantothenol) Inhibits Growth of the Intraerythrocytic Malaria Parasite

    PubMed Central

    Saliba, Kevin J.; Ferru, Isabelle; Kirk, Kiaran

    2005-01-01

    Pantothenic acid, a precursor of the crucial enzyme cofactor coenzyme A, is one of a relatively few nutrients for which the intraerythrocytic parasite has an absolute and acute requirement from the external medium. In some organisms the provitamin pantothenol can serve as a source of pantothenic acid; however, this was not the case for the human malaria parasite Plasmodium falciparum. Instead, pantothenol inhibited the in vitro growth of P. falciparum via a mechanism that involves competition with pantothenate and which can be attributed to inhibition of the parasite's pantothenate kinase. Oral administration of pantothenol to mice infected with the murine parasite Plasmodium vinckei vinckei resulted in a significant inhibition of parasite proliferation. This study highlights the potential of the coenzyme A biosynthesis pathway in general, and pantothenate kinase in particular, as an antimalarial drug target. PMID:15673744

  7. Provitamin B5 (pantothenol) inhibits growth of the intraerythrocytic malaria parasite.

    PubMed

    Saliba, Kevin J; Ferru, Isabelle; Kirk, Kiaran

    2005-02-01

    Pantothenic acid, a precursor of the crucial enzyme cofactor coenzyme A, is one of a relatively few nutrients for which the intraerythrocytic parasite has an absolute and acute requirement from the external medium. In some organisms the provitamin pantothenol can serve as a source of pantothenic acid; however, this was not the case for the human malaria parasite Plasmodium falciparum. Instead, pantothenol inhibited the in vitro growth of P. falciparum via a mechanism that involves competition with pantothenate and which can be attributed to inhibition of the parasite's pantothenate kinase. Oral administration of pantothenol to mice infected with the murine parasite Plasmodium vinckei vinckei resulted in a significant inhibition of parasite proliferation. This study highlights the potential of the coenzyme A biosynthesis pathway in general, and pantothenate kinase in particular, as an antimalarial drug target. PMID:15673744

  8. Mevalonates restore zoledronic acid-induced osteoclastogenesis inhibition.

    PubMed

    Nagaoka, Y; Kajiya, H; Ozeki, S; Ikebe, T; Okabe, K

    2015-04-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is likely to be caused by continuous imperfection of bone healing after surgical treatments in patients with long-term administration of nitrogen-containing bisphosphonates (NBPs). NBPs inhibit osteoclastic bone resorption by impairing the mevalonic acid sterol pathway in osteoclasts. Thus, we hypothesized that exogenous mevalonic acid metabolites restore the inhibitory effects of NBPs on osteoclastogenesis and bone remodeling. To clarify the effects of mevalonic acid metabolites, especially geranylgeranyl pyrophosphate (GGPP) and geranylgeranyl transferase substrate geranylgeranyl acid (GGOH), we examined the effects of zoledronic acid with or without GGOH or GGPP on osteoclast differentiation, multinucleation, and bone mineral deposition in tooth-extracted sockets. Zoledronic acid decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells derived from mouse osteoclast precursors treated with receptor activator of nuclear factor-?B ligand and macrophage colony-stimulating factor. Zoledronic acid simultaneously suppressed not only the expressions of osteoclastic differentiation-related molecules such as TRAP, cathepsin K, calcitonin receptor, and vacuolar H-ATPase but also those of multinucleation-related molecules such as dendrocyte-expressed 7 transmembrane proteins and osteoclast stimulatory transmembrane protein. Treatment with GGOH or GGPP, but not farnesyl acid, restored the zoledronic acid-inhibited number of TRAP-positive multinuclear cells together with the expressions of these molecules. Although intraperitoneal administration of zoledronic acid and lipopolysaccharide into mice appeared to induce BRONJ-like lesions with empty bone lacunae and decreased mineral deposition in tooth-extracted socket, both GGOH and GGPP partially restored the inhibitory effects on zoledronic acid-related mineral deposition. These results suggest the potential of mevalonic acid metabolites as therapeutic agents for BRONJ. PMID:25535203

  9. All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells

    SciTech Connect

    Fujiki, Atsushi [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan)] [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Imamura, Toshihiko, E-mail: imamura@koto.kpu-m.ac.jp [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan)] [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Sakamoto, Kenichi; Kawashima, Sachiko; Yoshida, Hideki; Hirashima, Yoshifumi; Miyachi, Mitsuru; Yagyu, Shigeki; Nakatani, Takuya [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan)] [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Sugita, Kanji [Department of Pediatrics, University of Yamanashi, Yamanashi (Japan)] [Department of Pediatrics, University of Yamanashi, Yamanashi (Japan); Hosoi, Hajime [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan)] [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. Black-Right-Pointing-Pointer Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. Black-Right-Pointing-Pointer Increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1 were also observed. Black-Right-Pointing-Pointer MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. Black-Right-Pointing-Pointer Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2 Prime -deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein {alpha} (C/EBP{alpha}) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

  10. 5-Aminosalicylic acid inhibits TGF-?1 signalling in colorectal cancer cells

    Microsoft Academic Search

    Pim J. Koelink; Lukas J. A. C. Hawinkels; Eliza Wiercinska; Cornelis F. M. Sier; Peter ten Dijke; Cornelis B. H. W. Lamers; Daan W. Hommes; Hein W. Verspaget

    2010-01-01

    The transforming growth factor-? (TGF-?) pathway is an important pathway in the initiation and progression of colorectal cancer. We aimed to determine the effects of 5-aminosalicylic acid (5-ASA) on TGF-? signalling in colorectal cancer cells in vitro. 5-ASA inhibited TGF-?1 signalling in HCT116 cells and colonic fibroblasts, as judged by a TGF-?-specific reporter gene assay, plasminogen activator inhibitor-1 mRNA and

  11. Abscisic acid inhibits germination of mature Arabidopsis seeds by limiting the availability of energy and nutrients

    Microsoft Academic Search

    Alejandro Garciarrubio; Juan P. Legaria; Alejandra A. Covarrubias

    1997-01-01

    .   The addition of abscisic acid (ABA) to mature non-dormant seeds inhibits their germination. This effect of ABA might be related\\u000a to its natural function as an endogenous inhibitor of precocious germination during seed formation. In this work, we studied\\u000a how ABA affects the germination of mature seeds and the growth of nascent seedlings of Arabidopsisthaliana (L.) Heynh. Our findings

  12. Zoledronic acid inhibits pulmonary metastasis dissemination in a preclinical model of Ewing’s sarcoma via inhibition of cell migration

    PubMed Central

    2014-01-01

    Background Ewing’s sarcoma (ES) is the second most frequent primitive malignant bone tumor in adolescents with a very poor prognosis for high risk patients, mainly when lung metastases are detected (overall survival <15% at 5 years). Zoledronic acid (ZA) is a potent inhibitor of bone resorption which induces osteoclast apoptosis. Our previous studies showed a strong therapeutic potential of ZA as it inhibits ES cell growth in vitro and ES primary tumor growth in vivo in a mouse model developed in bone site. However, no data are available on lung metastasis. Therefore, the aim of this study was to determine the effect of ZA on ES cell invasion and metastatic properties. Methods Invasion assays were performed in vitro in Boyden’s chambers covered with Matrigel. Matrix Metalloproteinase (MMP) activity was analyzed by zymography in ES cell culture supernatant. In vivo, a relevant model of spontaneous lung metastases which disseminate from primary ES tumor was induced by the orthotopic injection of 106 human ES cells in the tibia medullar cavity of nude mice. The effect of ZA (50 ?g/kg, 3x/week) was studied over a 4-week period. Lung metastases were observed macroscopically at autopsy and analysed by histology. Results ZA induced a strong inhibition of ES cell invasion, probably due to down regulation of MMP-2 and ?9 activities as analyzed by zymography. In vivo, ZA inhibits the dissemination of spontaneous lung metastases from a primary ES tumor but had no effect on the growth of established lung metastases. Conclusion These results suggest that ZA could be used early in the treatment of ES to inhibit bone tumor growth but also to prevent the early metastatic events to the lungs. PMID:24612486

  13. Syzygium campanulatum korth methanolic extract inhibits angiogenesis and tumor growth in nude mice

    PubMed Central

    2013-01-01

    Background Syzygium campanulatum Korth (Myrtaceae) is an evergreen shrub rich in phenolics, flavonoid antioxidants, and betulinic acid. This study sought to investigate antiangiogenic and anti-colon cancer effects of S.C. standardized methanolic extract. Methods Betulinic acid was isolated from methanolic extract by crystallization and chromatography techniques. S.C. methanolic extract was analyzed by UV-Vis spectrophotometry, FTIR, LC-MS, and HPLC. Antiangiogenic effect was studied on rat aortic rings, matrigel tube formation, cell proliferation and migration, and expression of vascular endothelial growth factor (VEGF). Antitumor effect was studied using a subcutaneous tumor model of HCT 116 colorectal carcinoma cells established in nude mice. Results Analysis by HPLC, LC-MS and FTIR confirm presence of betulinic acid in S.C. methanolic extract. Quantitative analysis by HPLC indicates presence of betulinic acid in S.C. extract at 5.42?±?0.09% (w/w). Antiangiogenesis study showed potent inhibition of microvessels outgrowth in rat aortic rings, and studies on normal and cancer cells did not show any significant cytotoxic effect. Antiangiogenic effect was further confirmed by inhibition of tube formation on matrigel matrix that involves human endothelial cells (IC50?=?17.6?±?2.9 ?g/ml). S.C. extract also inhibited migration of endothelial cells and suppressed expression of VEGF. In vivo antiangiogenic study showed inhibition of new blood vessels in chicken embryo chorioallantoic membrane (CAM), and in vivo antitumor study showed significant inhibition of tumor growth due to reduction of intratumor blood vessels and induction of cell death. Conclusion Collectively, our results indicate S. campanulatum as antiangiogenic and antitumor candidate, and a new source of betulinic acid. PMID:23842450

  14. Determination of Compounds Inhibiting Bacterial Growth in Sterilized Medical Devices

    Microsoft Academic Search

    H. Shintani; E. Suzuki; M. Sakurai

    2003-01-01

    Summary Medical devices must be sterilized before shipping. During sterilization the quality of the medical device must be maintained. Polysulfone (PS) and polycarbonate (PC) are often used as materials for medical devices. It has been observed that compounds inhibiting bacterial growth are produced when PS or PC are sterilized by autoclaving or by use of ozone gas, especially when ozone

  15. Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas

    Microsoft Academic Search

    Cristina Blazquez; Luis Gonzalez-Feria; Luis Alvarez; Amador Haro; M. Llanos Casanova; Manuel Guzman

    Cannabinoids inhibit tumor angiogenesis in mice, but the mechanism of their antiangiogenic action is still unknown. Because the vascular endo- thelial growth factor (VEGF) pathway plays a critical role in tumor angiogenesis, here we studied whether cannabinoids affect it. As a first approach, cDNA array analysis showed that cannabinoid administration to mice bearing s.c. gliomas lowered the expression of various

  16. Inhibition of citrus fungal pathogens by using lactic acid bacteria.

    PubMed

    Gerez, C L; Carbajo, M S; Rollán, G; Torres Leal, G; Font de Valdez, G

    2010-08-01

    The effect of lactic acid bacteria (LAB) on pathogenic fungi was evaluated and the metabolites involved in the antifungal effect were characterized. Penicillium digitatum (INTA 1 to INTA 7) and Geotrichum citri-aurantii (INTA 8) isolated from decayed lemon from commercial packinghouses were treated with imazalil and guazatine to obtain strains resistant to these fungicides. The most resistant strains (4 fungal strains) were selected for evaluating the antifungal activity of 33 LAB strains, among which only 8 strains gave positive results. The antifungal activity of these LAB strains was related to the production of lactic acid, acetic acid, and phenyllactic acid (PLA). A central composite design and the response surface methodology were used to evaluate the inhibitory effect of the organic acids produced by the LAB cultures. The antifungal activity of lactic acid was directly related to its concentration; however, acetic acid and PLA showed a peak of activity at 52.5 and 0.8 mM, respectively, with inhibition rates similar to those obtained with Serenade((R)) (3.0 ppm) imazalil (50 ppm) and guazatine (50 ppm). Beyond the peak of activity, a reduction in effectiveness of both acetic acid and PLA was observed. Comparing the inhibition rate of the organic acids, PLA was about 66- and 600-fold more effective than acetic acid and lactic acid, respectively. This study presents evidences on the antifungal effect of selected LAB strains and their end products. Studies are currently being undertaken to evaluate the effectiveness in preventing postharvest diseases on citrus fruits. PMID:20722936

  17. Rapid auxin-induced root growth inhibition requires the TIR and AFB auxin receptors.

    PubMed

    Scheitz, Katharina; Lüthen, Hartwig; Schenck, Daniel

    2013-08-01

    We investigated the relation between auxin-induced gene expression and the rapid auxin-induced growth inhibition in Arabidopsis thaliana roots. The natural auxin indole-3-acetic acid (IAA) induced a strong activation of gene expression as visualized by the DR5rev::GFP reporter gene technique. This effect was specific for active auxins and was abolished in knockout mutants of the F-box auxin receptors. We measured the IAA-induced growth inhibition at high time resolution and show that the F-box auxin receptor mutants failed to display this effect. We conclude that the F-box auxin receptors are needed for the response. In hypocotyls, auxin induces an increase in elongation growth, and this effect has been earlier shown to be independent of the F-box receptors. Based on these findings, we discuss differences in the growth control modes in roots and shoots. We demonstrate that the rapid auxin-induced root growth inhibition, unlike the induction of growth in hypocotyls, requires the presence of the F-box auxin receptors. PMID:23925852

  18. 2-Alkynoic fatty acids inhibit Topoisomerase IB from Leishmania donovani

    PubMed Central

    Carballeira, Néstor M.; Cartagena, Michelle; Sanabria, David; Kaiser, Marcel; Tasdemir, Deniz; Prada, Christopher F.; Reguera, Rosa M.; Balaña-Fouce, Rafael

    2012-01-01

    2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC50 = 5.3 ± 0.7 ?M. The potency of LdTopIB inhibition follows the trend 2-ODA> 2-HDA> 2-TDA, indicating that the effectiveness of inhibition depends on the fatty acid carbon chain length. All of the studied 2-alkynoic fatty acids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC50 = 11.0 ?M), but it was less effective against other protozoa, Trypanosoma cruzi (IC50 = 48.1 ?M) and T. brucei rhodesiense (IC50 = 64.5 ?M). The antiprotozoal activity of the 2-alkynoic fatty acids, in general, followed the trend 2-ODA> 2-HDA> 2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound. PMID:22932312

  19. Effect of organic acids on the growth and fermentation of ethanologenic Escherichia coli LY01

    SciTech Connect

    Zaldivar, J.; Ingram, L.O.

    1999-07-01

    Hemicellulose residues can be hydrolyzed into a sugar syrup using dilute mineral acids. Although this syrup represents a potential feedstock for biofuel production, toxic compounds generated during hydrolysis limit microbial metabolism. Escherichia coli LY01, an ethanologenic biocatalyst engineered to ferment the mixed sugars in hemicellulose syrups, has been tested for resistance to selected organic acids that re present in hemicellulose hydrolysates. Compounds tested include aromatic acids derived from lignin (ferulic, gallic, 4-hydroxybenzoic, syringic, and vanillic acids), acetic acid from the hydrolysis of acetylxylan, and others derived from sugar destruction (furoic, formic, levulinic, and caproic acids). Toxicity was related to hydrophobicity. Combinations of acids were roughly additive as inhibitors of cell growth. When tested at concentrations that inhibited growth by 80%, none appeared to strongly inhibit glycolysis and energy generation, or to disrupt membrane integrity. Toxicity was not markedly affected by inoculum size or incubation temperature. The toxicity of all acids except gallic acid was reduced by an increase in initial pH (from pH 6.0 to pH 7.0 to pH 8.0). Together, these results are consistent with the hypothesis that both aliphatic and mononuclear organic acids inhibit growth and ethanol production in LY01 by collapsing ion gradients and increasing internal anion concentrations.

  20. Chemiluminescence inhibition assay for folic acid using flow injection analysis.

    PubMed

    Song, Zhenghua; Wang, Lin

    2003-01-01

    A new flow injection method for the determination of folic acid is described. A fast oxidation reaction occurred when folic acid was mixed with potassium ferricyanide generating ferrocyanide which then inhibited the chemiluminescent reaction of ferricyanide and luminol in alkaline medium. The decrease of chemiluminescence intensity was correlated with the folic acid concentration in the range 0.1-21 microg/mL; the detection limit for the assay was 0.03 microg/mL (3sigma). A complete analysis of folic acid, including sampling and washing, could be performed within 2 min with a relative standard deviation of less than 4.0%. The proposed method has been applied successfully to the determination of folic acid in pharmaceutical preparations. PMID:12892416

  1. IMPACT AND MODEL OF AIR POLLUTION BY SIMULATED ACID RAIN ON THE GROWTH OF ORCHID PLANTS1)

    Microsoft Academic Search

    A. Santi; T. June

    Acid rain is one of the secondary air pollutants that inhibits the growth of orchid plants. The general purpose of this research was to study response of vanda, dendrobium, and oncidium orchids to the simulated acid rain to determine the critical point of the plant growth. The specific purpose of this research was (1) to detect the SO2 and NO2

  2. Inhibition of protein synthesis may explain the bactericidal properties of hypochlorous acid produced by phagocytic cells

    SciTech Connect

    McKenna, S.M.; Davies, K.J.A.

    1986-05-01

    The authors find that hypochlorous acid (HOCl) and hydrogen peroxide (H/sub 2/O/sub 2/) inhibit protein synthesis in E. coli: HOCl is similarly ordered 10x more efficient than H/sub 2/O/sub 2/. This result may underlie the mechanism of bacterial killing by phagocytes, which use H/sub 2/O/sub 2/ and myeloperoxidase (MPO) to oxidize Cl/sup -/ to HOCl. Protein synthesis (/sup 3/H-leu incorporation) was completely inhibited by 50..mu..M HOCl, whereas 50..mu..M H/sub 2/O/sub 2/ only gave similarly ordered 10% inhibition. Complete inhibition by H/sub 2/O/sub 2/ was only observed at concentrations < 0.5 mM. HOCl was also a more potent inhibitor of cell growth (cultured in M9 medium + glucose) than was H/sub 2/O/sub 2/. No growth occurred at 50..mu..M HOCl: in contrast 0.5 mM H/sub 2/O/sub 2/ was required for similar results. During time-course experiments it was found that the inhibition of cell growth by both HOCl and H/sub 2/O/sub 2/ reached a maximum within 30 min (at any concentration used). HOCl reacts avidly with amino groups to form N-chloroamines but H/sub 2/O/sub 2/ is unreactive. Amino acids (ala, lys, met, trp) or taurine (all at 10 mM) prevented the effects of HOCl but did not affect H/sub 2/O/sub 2/ results. There was an excellent correlation between decreased protein synthesis and diminished cell growth. Inhibition of cell growth was not explained by proteolysis (release of acid-soluble counts), or by loss of membrane integrity. They propose that inhibition of protein synthesis may be a fundamental aspect of the bactericidal functions of phagocytes, and that the production of HOCl by MPO represents a quantitative advantage over H/sub 2/O/sub 2/.

  3. Targeting FAK scaffold functions inhibits human renal cell carcinoma growth.

    PubMed

    Béraud, Claire; Dormoy, Valérian; Danilin, Sabrina; Lindner, Véronique; Béthry, Audrey; Hochane, Mazène; Coquard, Catherine; Barthelmebs, Mariette; Jacqmin, Didier; Lang, Hervé; Massfelder, Thierry

    2015-10-01

    Human conventional renal cell carcinoma (CCC) remains resistant to current therapies. Focal Adhesion Kinase (FAK) is upregulated in many epithelial tumors and clearly implicated in nearly all facets of cancer. However, only few reports have assessed whether FAK may be associated with renal tumorigenesis. In this study, we investigated the potential role of FAK in the growth of human CCC using a panel of CCC cell lines expressing or not the von Hippel-Lindau (VHL) tumor suppressor gene as well as normal/tumoral renal tissue pairs. FAK was found constitutively expressed in human CCC both in culture cells and freshly harvested tumors obtained from patients. We showed that CCC cell growth was dramatically reduced in FAK-depleted cells or after FAK inhibition with various inhibitors and this effect was obtained through inhibition of cell proliferation and induction of cell apoptosis. Additionally, our results indicated that FAK knockdown decreased CCC cell migration and invasion. More importantly, depletion or pharmacological inhibition of FAK substantially inhibited tumor growth in vivo. Interestingly, investigations of the molecular mechanism revealed loss of FAK phosphorylation during renal tumorigenesis impacting multiple signaling pathways. Taken together, our findings reveal a previously uncharacterized role of FAK in CCC whereby FAK exerts oncogenic properties through a non canonical signaling pathway involving its scaffolding kinase-independent properties. Therefore, targeting the FAK scaffold may represent a promising approach for developing innovative and highly specific therapies in human CCC. PMID:25809490

  4. Inhibition of Fatty Acid Metabolism Reduces Human Myeloma Cells Proliferation

    PubMed Central

    Tirado-Vélez, José Manuel; Joumady, Insaf; Sáez-Benito, Ana; Cózar-Castellano, Irene; Perdomo, Germán

    2012-01-01

    Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of ?-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited ?-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40–70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma. PMID:23029529

  5. Inhibition of arachidonic acid metabolism in colonic inflammation

    SciTech Connect

    Phyall, W.B.; Rush, J.A.; Fondacaro, J.D.

    1986-03-01

    The authors have previously identified a lipoxygenase product profile in the acetic acid-induced model of colonic inflammation in the rat and have demonstrated utility of this model in evaluating inhibitors of arachidonic acid (AA) metabolism under in vitro conditions. They now demonstrate efficacy of an inhibitor of AA metabolism in this model under in vivo conditions. Male rats were pretreated with either nordihydroguaiaretic acid (NDGA) (50 mg/kg, p.o.) or vehicle for 3 consecutive days prior to induction of colonic inflammation with intraluminal administration of 2 mls of 5% acetic acid. After sacrifice, colonic mucosa was removed and incubated in the presence and absence of Ca/sup 2 +/ ionophore, A23187 (2 ..mu..M) for 5 min at 37/sup 0/C. Production of AA metabolites (LTB/sub 4/, 5-HETE, PGE/sub 2/, TxB/sub 2/) was determined by high pressure liquid chromatography and radioimmunoassay. NDGA treatment caused a significant inhibition of metabolite production (LTB/sub 4/, 5-HETE, PGE/sub 2/, TxB/sub 2/) compared to vehicle controls. This inhibition was evident in both ionophore-stimulated and non-stimulated samples. These results show that intestinal AA metabolism can be inhibited by in vivo drug administration and further suggest that this animal model may provide a simple means for evaluating potential therapies for inflammatory bowel disease.

  6. Inhibition of Fatty Acid Synthesis in Bovine Mammary Homogenate by Palmitic Acid is Not a Detergent Effect

    Microsoft Academic Search

    T. C. Wright; J. P. Cant; B. W. McBride

    2002-01-01

    Supplemental fat fed to dairy cows affects the fat composition of milk by reducing the yield of mammary synthesized fatty acids. The effect has been attributed to a potential allosteric inhibition of acetyl coenzyme- A, a key enzyme in fatty acid synthesis. In vitro experi- ments have demonstrated an inhibition of fatty acid synthesis when long-chain fatty acids are added

  7. Effects of abscisic acid on growth and dehydration tolerance of Cynanchum komarovii seedlings

    Microsoft Academic Search

    L. Yang; C. L. Yu; F. Shi; Y. Q. Wei; C. C. Wang; H. T. Hu; C. G. Cheng

    2007-01-01

    Cynanchum komarovii is well adapted to hot and dry adverse environments. To determine if exogenous abscisic acid (ABA) affects the growth and\\u000a dehydration tolerance of this wild plant, ABA was added into the hydroponic solution at a final concentration of 10 ?M for\\u000a 14 days. Root growth is less inhibited than shoot growth under well-watered condition by ABA treatment. ABA reduced

  8. Growth temperature affects accumulation of exogenous fatty acids and fatty acid composition in Schizosaccharomyces pombe

    Microsoft Academic Search

    Virginia M. McDonough; Therese M. Roth

    2004-01-01

    The incorporation of exogenously supplied fatty acids, palmitic acid, palmitoleic acid, oleic acid and linoleic acid, was examined in the yeast Schizosaccharomyces pombe at two growth temperatures, 20 °C and 30 °C. Fatty acids supplied to S. pombe in the growth medium were found to be preferentially incorporated into the cells, becoming a dominant species. The relative increase in exogenous

  9. New simulation model of multicomponent crystal growth and inhibition.

    PubMed

    Wathen, Brent; Kuiper, Michael; Walker, Virginia; Jia, Zongchao

    2004-04-01

    We review a novel computational model for the study of crystal structures both on their own and in conjunction with inhibitor molecules. The model advances existing Monte Carlo (MC) simulation techniques by extending them from modeling 3D crystal surface patches to modeling entire 3D crystals, and by including the use of "complex" multicomponent molecules within the simulations. These advances makes it possible to incorporate the 3D shape and non-uniform surface properties of inhibitors into simulations, and to study what effect these inhibitor properties have on the growth of whole crystals containing up to tens of millions of molecules. The application of this extended MC model to the study of antifreeze proteins (AFPs) and their effects on ice formation is reported, including the success of the technique in achieving AFP-induced ice-growth inhibition with concurrent changes to ice morphology that mimic experimental results. Simulations of ice-growth inhibition suggest that the degree of inhibition afforded by an AFP is a function of its ice-binding position relative to the underlying anisotropic growth pattern of ice. This extended MC technique is applicable to other crystal and crystal-inhibitor systems, including more complex crystal systems such as clathrates. PMID:15054746

  10. Apicoplast-Targeting Antibacterials Inhibit the Growth of Babesia Parasites

    PubMed Central

    AbouLaila, Mahmoud; Munkhjargal, Tserendorj; Sivakumar, Thillaiampalam; Ueno, Akio; Nakano, Yuki; Yokoyama, Miki; Yoshinari, Takeshi; Nagano, Daisuke; Katayama, Koji; El-Bahy, Nasr; Yokoyama, Naoaki

    2012-01-01

    The apicoplast housekeeping machinery, specifically apicoplast DNA replication, transcription, and translation, was targeted by ciprofloxacin, thiostrepton, and rifampin, respectively, in the in vitro cultures of four Babesia species. Furthermore, the in vivo effect of thiostrepton on the growth cycle of Babesia microti in BALB/c mice was evaluated. The drugs caused significant inhibition of growth from an initial parasitemia of 1% for Babesia bovis, with 50% inhibitory concentrations (IC50s) of 8.3, 11.5, 12, and 126.6 ?M for ciprofloxacin, thiostrepton, rifampin, and clindamycin, respectively. The IC50s for the inhibition of Babesia bigemina growth were 15.8 ?M for ciprofloxacin, 8.2 ?M for thiostrepton, 8.3 ?M for rifampin, and 206 ?M for clindamycin. The IC50s for Babesia caballi were 2.7 ?M for ciprofloxacin, 2.7 ?M for thiostrepton, 4.7 ?M for rifampin, and 4.7 ?M for clindamycin. The IC50s for the inhibition of Babesia equi growth were 2.5 ?M for ciprofloxacin, 6.4 ?M for thiostrepton, 4.1 ?M for rifampin, and 27.2 ?M for clindamycin. Furthermore, an inhibitory effect was revealed for cultures with an initial parasitemia of either 10 or 7% for Babesia bovis or Babesia bigemina, respectively. The three inhibitors caused immediate death of Babesia bovis and Babesia equi. The inhibitory effects of ciprofloxacin, thiostrepton, and rifampin were confirmed by reverse transcription-PCR. Thiostrepton at a dose of 500 mg/kg of body weight resulted in 77.5% inhibition of Babesia microti growth in BALB/c mice. These results implicate the apicoplast as a potential chemotherapeutic target for babesiosis. PMID:22391527

  11. Apicoplast-targeting antibacterials inhibit the growth of Babesia parasites.

    PubMed

    Aboulaila, Mahmoud; Munkhjargal, Tserendorj; Sivakumar, Thillaiampalam; Ueno, Akio; Nakano, Yuki; Yokoyama, Miki; Yoshinari, Takeshi; Nagano, Daisuke; Katayama, Koji; El-Bahy, Nasr; Yokoyama, Naoaki; Igarashi, Ikuo

    2012-06-01

    The apicoplast housekeeping machinery, specifically apicoplast DNA replication, transcription, and translation, was targeted by ciprofloxacin, thiostrepton, and rifampin, respectively, in the in vitro cultures of four Babesia species. Furthermore, the in vivo effect of thiostrepton on the growth cycle of Babesia microti in BALB/c mice was evaluated. The drugs caused significant inhibition of growth from an initial parasitemia of 1% for Babesia bovis, with 50% inhibitory concentrations (IC(50)s) of 8.3, 11.5, 12, and 126.6 ?M for ciprofloxacin, thiostrepton, rifampin, and clindamycin, respectively. The IC(50)s for the inhibition of Babesia bigemina growth were 15.8 ?M for ciprofloxacin, 8.2 ?M for thiostrepton, 8.3 ?M for rifampin, and 206 ?M for clindamycin. The IC(50)s for Babesia caballi were 2.7 ?M for ciprofloxacin, 2.7 ?M for thiostrepton, 4.7 ?M for rifampin, and 4.7 ?M for clindamycin. The IC(50)s for the inhibition of Babesia equi growth were 2.5 ?M for ciprofloxacin, 6.4 ?M for thiostrepton, 4.1 ?M for rifampin, and 27.2 ?M for clindamycin. Furthermore, an inhibitory effect was revealed for cultures with an initial parasitemia of either 10 or 7% for Babesia bovis or Babesia bigemina, respectively. The three inhibitors caused immediate death of Babesia bovis and Babesia equi. The inhibitory effects of ciprofloxacin, thiostrepton, and rifampin were confirmed by reverse transcription-PCR. Thiostrepton at a dose of 500 mg/kg of body weight resulted in 77.5% inhibition of Babesia microti growth in BALB/c mice. These results implicate the apicoplast as a potential chemotherapeutic target for babesiosis. PMID:22391527

  12. Macrokinetics of magnesium sulfite oxidation inhibited by ascorbic acid.

    PubMed

    Lidong, Wang; Yongliang, Ma; Wendi, Zhang; Qiangwei, Li; Yi, Zhao; Zhanchao, Zhang

    2013-08-15

    Magnesia flue gas desulfurization is a promising process for small to medium scale industrial coal-fired boilers in order to reduce sulfur dioxide emissions, in which oxidation control of magnesium sulfite is of great importance for the recycling of products. Effects of four inhibitors were compared by kinetic experiments indicating that ascorbic acid is the best additive, which retards the oxidation process of magnesium sulfite in trace presence. The macrokinetics of magnesium sulfite oxidation inhibited by ascorbic acid were studied. Effects of the factors, including ascorbic acid concentration, magnesium sulfite concentration, oxygen partial pressure, pH, and temperature, were investigated in a stirred reactor with bubbling. The results show that the reaction rate is -0.55 order in ascorbic acid, 0.77 in oxygen partial pressure, and zero in magnesium sulfite concentration, respectively. The apparent activation energy is 88.0 kJ mol(-1). Integrated with the kinetic model, it is concluded that the oxidation rate of magnesium sulfite inhibited by ascorbic acid is controlled by the intrinsic chemical reaction. The result provides a useful reference for sulfite recovery in magnesia desulfurization. PMID:23692683

  13. D-amino acids inhibit initial bacterial adhesion: thermodynamic evidence.

    PubMed

    Xing, Su-Fang; Sun, Xue-Fei; Taylor, Alicia A; Walker, Sharon L; Wang, Yi-Fu; Wang, Shu-Guang

    2015-04-01

    Bacterial biofilms are structured communities of cells enclosed in a self-produced hydrated polymeric matrix that can adhere to inert or living surfaces. D-Amino acids were previously identified as self-produced compounds that mediate biofilm disassembly by causing the release of the protein component of the polymeric matrix. However, whether exogenous D-amino acids could inhibit initial bacterial adhesion is still unknown. Here, the effect of the exogenous amino acid D-tyrosine on initial bacterial adhesion was determined by combined use of chemical analysis, force spectroscopic measurement, and theoretical predictions. The surface thermodynamic theory demonstrated that the total interaction energy increased with more D-tyrosine, and the contribution of Lewis acid-base interactions relative to the change in the total interaction energy was much greater than the overall nonspecific interactions. Finally, atomic force microscopy analysis implied that the hydrogen bond numbers and adhesion forces decreased with the increase in D-tyrosine concentrations. D-Tyrosine contributed to the repulsive nature of the cell and ultimately led to the inhibition of bacterial adhesion. This study provides a new way to regulate biofilm formation by manipulating the contents of D-amino acids in natural or engineered systems. PMID:25333717

  14. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis

    PubMed Central

    XIAN, SHU-LIN; CAO, WEI; ZHANG, XIAO-DONG; LU, YUN-FEI

    2015-01-01

    Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore, the inhibition of glycolysis may inhibit tumor growth. Our previous study demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell proliferation in vitro. However, the ability of 3-BrPA to suppress tumor growth in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the present study was to investigate the inhibitory effect of 3-BrPA in an animal model of gastric cancer. It was identified that 3-BrPA exhibited strong inhibitory effects upon xenograft tumor growth in nude mice. In addition, the antitumor function of 3-BrPA exhibited a dose-effect association, which was similar to that of the chemotherapeutic agent, 5-fluorouracil. Furthermore, 3-BrPA exhibited low toxicity in the blood, liver and kidneys of the nude mice. The present study hypothesized that the inhibitory effect of 3-BrPA is achieved through the inhibition of hexokinase activity, which leads to the downregulation of B-cell lymphoma 2 (Bcl-2) expression, the upregulation of Bcl-2-associated X protein expression and the subsequent activation of caspase-3. These data suggest that 3-BrPA may be a novel therapy for the treatment of gastric cancer. PMID:25621044

  15. Proteasome Inhibition by Fellutamide B Induces Nerve Growth Factor Synthesis

    PubMed Central

    Hines, John; Groll, Michael; Fahnestock, Margaret; Crews, Craig M.

    2008-01-01

    SUMMARY Neurotrophic small molecules have the potential to aid in the treatment of neuronal injury and neurodegenerative diseases. The natural product fellutamide B, originally isolated from Penicillium fellutanum, potently induces nerve growth factor (NGF) release from fibroblasts and glial-derived cells, although the mechanism for this neurotrophic activity has not been elucidated. Here, we report that fellutamide B potently inhibits proteasome catalytic activity. High resolution structural information obtained from co-crystallization of the 20S proteasome reveals novel aspects regarding ?-subunit binding and adduct formation by fellutamide B to inhibit their hydrolytic activity. We demonstrate that fellutamide B and other proteasome inhibitors increased NGF gene transcription via a cis-acting element (or elements) in the promoter. These results demonstrate an unrecognized connection between proteasome inhibition and NGF production, suggesting a possible new strategy in the development of neurotrophic agents. PMID:18482702

  16. Hydroxyapatite-binding peptides for bone growth and inhibition

    DOEpatents

    Bertozzi, Carolyn R. (Berkeley, CA); Song, Jie (Shrewsbury, MA); Lee, Seung-Wuk (Walnut Creek, CA)

    2011-09-20

    Hydroxyapatite (HA)-binding peptides are selected using combinatorial phage library display. Pseudo-repetitive consensus amino acid sequences possessing periodic hydroxyl side chains in every two or three amino acid sequences are obtained. These sequences resemble the (Gly-Pro-Hyp).sub.x repeat of human type I collagen, a major component of extracellular matrices of natural bone. A consistent presence of basic amino acid residues is also observed. The peptides are synthesized by the solid-phase synthetic method and then used for template-driven HA-mineralization. Microscopy reveal that the peptides template the growth of polycrystalline HA crystals .about.40 nm in size.

  17. CDK1-cyclin B1 mediates the inhibition of proliferation induced by omega-3 fatty acids in MDA-MB-231 breast cancer cells

    Microsoft Academic Search

    Aurélia Barascu; Pierre Besson; Olivier Le Floch; Philippe Bougnoux; Marie-Lise Jourdan

    2006-01-01

    Long-chain omega-3 polyunsaturated fatty acids are thought to inhibit the development of breast cancer. We investigated the effects of docosahexaenoic and eicosapentaenoic acids on the proliferation of MDA-MB-231 human mammary epithelial cells. Both docosahexaenoic and eicosapentaenoic acids decreased cell growth with a higher efficiency for docosahexaenoic acid (87% at 100?M versus 74% for eicosapentaenoic acid). The effect on specific cell

  18. Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma.

    PubMed

    Zhu, Li Ming; Shi, Dong Mei; Dai, Qiang; Cheng, Xiao Jiao; Yao, Wei Yan; Sun, Ping Hu; Ding, Yanfei; Qiao, Min Min; Wu, Yun Lin; Jiang, Shi Hu; Tu, Shui Ping

    2014-07-30

    X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1), a XIAP-binding protein, is a tumor suppressor gene. XAF1 was silent or expressed lowly in most human malignant tumors. However, the role of XAF1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the effect of XAF1 on tumor growth and angiogenesis in hepatocellular cancer cells. Our results showed that XAF1 expression was lower in HCC cell lines SMMC-7721, Hep G2 and BEL-7404 and liver cancer tissues than that in paired non-cancer liver tissues. Adenovirus-mediated XAF1 expression (Ad5/F35-XAF1) significantly inhibited cell proliferation and induced apoptosis in HCC cells in dose- and time- dependent manners. Infection of Ad5/F35-XAF1 induced cleavage of caspase -3, -8, -9 and PARP in HCC cells. Furthermore, Ad5/F35-XAF1 treatment significantly suppressed tumor growth in a xenograft model of liver cancer cells. Western Blot and immunohistochemistry staining showed that Ad5/F35-XAF1 treatment suppressed expression of vascular endothelial growth factor (VEGF), which is associated with tumor angiogenesis, in cancer cells and xenograft tumor tissues. Moreover, Ad5/F35-XAF1 treatment prolonged the survival of tumor-bearing mice. Our results demonstrate that XAF1 inhibits tumor growth by inducing apoptosis and inhibiting tumor angiogenesis. XAF1 may be a promising target for liver cancer treatment. PMID:24980821

  19. Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma

    PubMed Central

    Zhu, Li Ming; Shi, Dong Mei; Dai, Qiang; Cheng, Xiao Jiao; Yao, Wei Yan; Sun, Ping Hu; Ding, Yan Fei; Qiao, Min Min; Wu, Yun Lin; Jiang, Shi Hu; Tu, Shui Ping

    2014-01-01

    X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1), a XIAP-binding protein, is a tumor suppressor gene. XAF1 was silent or expressed lowly in most human malignant tumors. However, the role of XAF1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the effect of XAF1 on tumor growth and angiogenesis in hepatocellular cancer cells. Our results showed that XAF1 expression was lower in HCC cell lines SMMC-7721, Hep G2 and BEL-7404 and liver cancer tissues than that in paired non-cancer liver tissues. Adenovirus-mediated XAF1 expression (Ad5/F35-XAF1) significantly inhibited cell proliferation and induced apoptosis in HCC cells in dose- and time- dependent manners. Infection of Ad5/F35-XAF1 induced cleavage of caspase -3, -8, -9 and PARP in HCC cells. Furthermore, Ad5/F35-XAF1 treatment significantly suppressed tumor growth in a xenograft model of liver cancer cells. Western Blot and immunohistochemistry staining showed that Ad5/F35-XAF1 treatment suppressed expression of vascular endothelial growth factor (VEGF), which is associated with tumor angiogenesis, in cancer cells and xenograft tumor tissues. Moreover, Ad5/F35-XAF1 treatment prolonged the survival of tumor-bearing mice. Our results demonstrate that XAF1 inhibits tumor growth by inducing apoptosis and inhibiting tumor angiogenesis. XAF1 may be a promising target for liver cancer treatment. PMID:24980821

  20. Toxicity Assay in Kraft E1 Effluent Treated by Ozone: Algae Growth Inhibition and Cytotoxicity in V79 Cells

    Microsoft Academic Search

    Márcia Regina Assalin; João Batista Fabrin-Neto; Nelson Durán; Marcela Haun

    2007-01-01

    The efficiency of an ozonation process in the degradation of the Kraft E1 effluent was evaluated. The investigation was focused on the reduction of chemical oxygen demand, total phenols, color and the absorbance at 254 nm. The chronic toxicity was evaluated by growth inhibition of algae Selenatrum capricornutum and cytotoxicity evaluation of effluents samples by determination of the nucleic acid

  1. FH535 inhibited metastasis and growth of pancreatic cancer cells

    PubMed Central

    Wu, Meng-Yao; Liang, Rong-Rui; Chen, Kai; Shen, Meng; Tian, Ya-Li; Li, Dao-Ming; Duan, Wei-Ming; Gui, Qi; Gong, Fei-Ran; Lian, Lian; Li, Wei; Tao, Min

    2015-01-01

    FH535 is a small-molecule inhibitor of the Wnt/?-catenin signaling pathway, which a substantial body of evidence has proven is activated in various cancers, including pancreatic cancer. Activation of the Wnt/?-catenin pathway plays an important role in tumor progression and metastasis. We investigated the inhibitory effect of FH535 on the metastasis and growth of pancreatic cancer cells. Western blotting and luciferase reporter gene assay indicated that FH535 markedly inhibited Wnt/?-catenin pathway viability in pancreatic cancer cells. In vitro wound healing, invasion, and adhesion assays revealed that FH535 significantly inhibited pancreatic cancer cell metastasis. We also observed the inhibitory effect of FH535 on pancreatic cancer cell growth via the tetrazolium and plate clone formation assays. Microarray analyses suggested that changes in the expression of multiple genes could be involved in the anti-cancer effect of FH535 on pancreatic cancer cells. Our results indicate for the first time that FH535 inhibits pancreatic cancer cell metastasis and growth, providing new insight into therapy of pancreatic cancer. PMID:26185454

  2. Ricinoleic acid inhibits methanogenesis and fatty acid biohydrogenation in ruminal digesta from sheep and in bacterial cultures.

    PubMed

    Ramos Morales, E; Mata Espinosa, M A; McKain, N; Wallace, R J

    2012-12-01

    Ricinoleic acid (RA; 12-hydroxy-cis-9-18:1) is the main fatty acid component of castor oil. Although a precursor for CLA synthesis in lactic acid bacteria, RA was found previously not to form CLA in ruminal digesta but to have some inhibitory properties. The present study was undertaken to evaluate the potential of RA to modulate ruminal biohydrogenation and methanogenesis. Ruminal digesta from 4 sheep receiving a mixed hay-concentrate diet was incubated in vitro with 0.167 g/L of linoleic acid (LA; cis-9,cis-12-18:2) or with a combination of LA and RA or LA and castor oil (LA, RA, and castor oil added to a final concentration of 0.167 g/L) in the presence and absence of lipase. The CLA rumenic acid (cis-9,trans-11-18:2) accumulated when either RA or castor oil and lipase was present. Vaccenic acid (VA; trans-11-18:1) also accumulated, and a decrease of the rate of production of stearic acid (SA; 18:0) was observed. When LA was incubated with castor oil in the absence of lipase, no effects on biohydrogenation were observed. Ricinoleic acid at 0.02 g/L did not affect growth of Butyrivibrio fibrisolvens but it inhibited growth of Butyrivibrio proteoclasticus. Butyrivibrio proteoclasticus but not B. fibrisolvens metabolized RA to 12-hydroxystearate. Linoleic acid metabolism by B. proteoclasticus appeared to be unaffected by RA addition whereas rumenic acid accumulation increased (P = 0.015 at 12 h) when RA was added. A 28% decrease (P = 0.004) in methane was obtained in 24 h in vitro incubations of diluted buffered ruminal fluid with added 0.2 g RA/L. There was no effect on the total concentration of VFA after 24 h as a result of RA addition, but the molar proportions of acetate and butyrate were decreased (P = 0.041 and P < 0.001, respectively) whereas that of propionate increased (P < 0.001). It was concluded that, at least in vitro, RA or the combination of castor oil and lipase inhibit biohydrogenation, causing the accumulation of rumenic acid and VA, with potential health benefits for ruminant products. The effect appeared to be mediated via an inhibitory effect on the biohydrogenating activity of B. proteoclasticus. An added environmental benefit could be a concomitant decrease in methane emissions. In vivo studies are now required to confirm the potential of these additives. PMID:22829608

  3. Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth

    PubMed Central

    Aronin, Alexandra; Amsili, Shira; Prigozhina, Tatyana B.; Tzdaka, Kobi; Rachmilewitz, Jacob; Shani, Noam; Tykocinski, Mark L.; Dranitzki Elhalel, Michal

    2013-01-01

    Background New strategies for the treatment of hepatocellular carcinoma (HCC) are needed, given that currently available chemotherapeutics are inefficient. Since tumor growth reflects the net balance between pro-proliferative and death signaling, agents shifting the equilibrium toward the latter are of considerable interest. The TWEAK:Fn14 signaling axis promotes tumor cell proliferation and tumor angiogenesis, while TRAIL:TRAIL-receptor (TRAIL-R) interactions selectively induce apoptosis in malignant cells. Fn14•TRAIL, a fusion protein bridging these two pathways, has the potential to inhibit tumor growth, by interfering with TWEAK:Fn14 signaling, while at the same time enforcing TRAIL:TRAIL-R-mediated apoptosis. Consequently, Fn14•TRAIL's capacity to inhibit HCC growth was tested. Results Fn14•TRAIL induced robust apoptosis of multiple HCC cell lines, while sparing non-malignant hepatocyte cell lines. Differential susceptibility to this agent did not correlate with expression levels of TRAIL, TRAIL-R, TWEAK and Fn14 by these lines. Fn14•TRAIL was more potent than soluble TRAIL, soluble Fn14, or a combination of the two. The requirement of both of Fn14•TRAIL's molecular domains for function was established using blocking antibodies directed against each of them. Subcutaneous injection of Fn14•TRAIL abrogated HCC growth in a xenograft model, and was well tolerated by the mice. Conclusions In this study, Fn14•TRAIL, a multifunctional fusion protein originally designed to treat autoimmunity, was shown to inhibit the growth of HCC, both in vitro and in vivo. The demonstration of this fusion protein’s potent anti-tumor activity suggests that simultaneous targeting of two signaling axes by a single fusion can serve as a basis for highly effective anti-cancer therapies. PMID:24130833

  4. Chlamydia trachomatis growth depends on eukaryotic cholesterol esterification and is affected by Acyl-CoA:cholesterol acyltransferase inhibition.

    PubMed

    Peters, Jan; Byrne, Gerald I

    2015-08-01

    Chlamydia trachomatis is auxotrophic for a variety of essential metabolites. Inhibitors that interrupt host cell catabolism may inhibit chlamydial growth and reveal Chlamydia metabolite requirements. We used the known indoleamine-2,3-dioxygenase (IDO)-inhibitor 4-phenyl imidazole (4-PI) to reverse Interferon (IFN)-?-induced chlamydial growth inhibition. However, at elevated inhibitor concentrations chlamydial growth was arrested even in the absence of IFN-?. Since 4-PI is known to interfere with cholesterol metabolism, the effect of cholesterol add-back was tested. Chlamydia growth was restored in the presence of cholesterol in serum-containing, but not serum-free medium suggesting that cholesterol and other serum components are required for growth recovery. When serum factors were tested, either cholesteryl linoleate or the combination of cholesterol and linoleic acid restored chlamydial growth. However, growth was not restored when either cholesterol or linoleic acid were added alone, suggesting that the production of cholesteryl esters from cholesterol and fatty acids was affected by 4-PI treatment. In eukaryotic cells, the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes the production of cholesteryl esters. When HeLa cells were treated with the ACAT-specific inhibitor 4-hydroxycinnamicacid amide C. trachomatis growth was interrupted, but was restored by the addition of cholesteryl linoleate, suggesting that ACAT activity is necessary for intracellular Chlamydia growth. PMID:25883118

  5. Targeting Aurora Kinase with MK-0457 Inhibits Ovarian Cancer Growth

    PubMed Central

    Lin, Yvonne G.; Immaneni, Anand; Merritt, William M.; Mangala, Lingegowda S.; Kim, SeungWook; Shahzad, Mian M.K.; Tsang, Yvonne T.M.; Armaiz-Pena, Guillermo N.; Lu, Chunhua; Kamat, Aparna A.; Han, Liz Y.; Spannuth, WhitneyA.; Nick, Alpa M.; Landen, Charles N.; Wong, Kwong K.; Gray, Michael J.; Coleman, Robert L.; Bodurka, Diane C.; Brinkley, William R.; Sood, Anil K.

    2009-01-01

    Purpose The Aurora kinase family plays pivotal roles in mitotic integrity and cell cycle.We sought to determine the effects of inhibiting Aurora kinase on ovarian cancer growth in an orthotopic mouse model using a small molecule pan-Aurora kinase inhibitor, MK-0457. Experimental Design We examined cell cycle regulatory effects and ascertained the therapeutic efficacy of Aurora kinase inhibition both alone and combined with docetaxel using both in vitro and in vivo ovarian cancer models. Results In vitro cytotoxicity assays with HeyA8 and SKOV3ip1 cells revealed >10-fold greater docetaxel cytotoxicity in combination with MK-0457. After in vivo dose kinetics were determined using phospho-histone H3 status, therapy experiments with the chemosensitive HeyA8 and SKOV3ip1as well as the chemoresistant HeyA8-MDR and A2780-CP20 models showed that Aurora kinase inhibition alone significantly reduced tumor burden compared with controls (P values < 0.01). Combination treatment with docetaxel resulted in significantly improved reduction in tumor growth beyond that afforded by docetaxel alone (P ? 0.03). Proliferating cell nuclear antigen immunohistochemistry revealed that MK-0457 alone and in combination with docetaxel significantly reduced cellular proliferation (P values < 0.001). Compared with controls, treatment with MK-0457 alone and in combination with docetaxel also significantly increased tumor cell apoptosis by ?3-fold (P < 0.01). Remarkably, compared with docetaxel monotherapy, MK-0457 combined with docetaxel resulted in significantly increased tumor cell apoptosis. Conclusions Aurora kinase inhibition significantly reduces tumor burden and cell proliferation and increases tumor cell apoptosis in this preclinical orthotopic model of ovarian cancer. The role of Aurora kinase inhibition in ovarian cancer merits further investigation in clinical trials. PMID:18765535

  6. Antibacterial activity of lichen secondary metabolite usnic acid is primarily caused by inhibition of RNA and DNA synthesis.

    PubMed

    Maci?g-Dorszy?ska, Monika; W?grzyn, Grzegorz; Guzow-Krzemi?ska, Beata

    2014-04-01

    Usnic acid, a compound produced by various lichen species, has been demonstrated previously to inhibit growth of different bacteria and fungi; however, mechanism of its antimicrobial activity remained unknown. In this report, we demonstrate that usnic acid causes rapid and strong inhibition of RNA and DNA synthesis in Gram-positive bacteria, represented by Bacillus subtilis and Staphylococcus aureus, while it does not inhibit production of macromolecules (DNA, RNA, and proteins) in Escherichia coli, which is resistant to even high doses of this compound. However, we also observed slight inhibition of RNA synthesis in a Gram-negative bacterium, Vibrio harveyi. Inhibition of protein synthesis in B. subtilis and S. aureus was delayed, which suggest indirect action (possibly through impairment of transcription) of usnic acid on translation. Interestingly, DNA synthesis was halted rapidly in B. subtilis and S. aureus, suggesting interference of usnic acid with elongation of DNA replication. We propose that inhibition of RNA synthesis may be a general mechanism of antibacterial action of usnic acid, with additional direct mechanisms, such as impairment of DNA replication in B. subtilis and S. aureus. PMID:24571086

  7. Epidermal growth factor receptor endocytic traffic perturbation by phosphatidate phosphohydrolase inhibition: new strategy against cancer.

    PubMed

    Shaughnessy, Ronan; Retamal, Claudio; Oyanadel, Claudia; Norambuena, Andrés; López, Alejandro; Bravo-Zehnder, Marcela; Montecino, Fabian J; Metz, Claudia; Soza, Andrea; González, Alfonso

    2014-05-01

    Epidermal growth factor receptor (EGFR) exaggerated (oncogenic) function is currently targeted in cancer treatment with drugs that block receptor ligand binding or tyrosine kinase activity. Because endocytic trafficking is a crucial regulator of EGFR function, its pharmacological perturbation might provide a new anti-tumoral strategy. Inhibition of phosphatidic acid (PA) phosphohydrolase (PAP) activity has been shown to trigger PA signaling towards type 4 phosphodiesterase (PDE4) activation and protein kinase A inhibition, leading to internalization of empty/inactive EGFR. Here, we used propranolol, its l- and d- isomers and desipramine as PAP inhibitors to further explore the effects of PAP inhibition on EGFR endocytic trafficking and its consequences on EGFR-dependent cancer cell line models. PAP inhibition not only made EGFR inaccessible to stimuli but also prolonged the signaling lifetime of ligand-activated EGFR in recycling endosomes. Strikingly, such endocytic perturbations applied in acute/intermittent PAP inhibitor treatments selectively impaired cell proliferation/viability sustained by an exaggerated EGFR function. Phospholipase D inhibition with FIPI (5-fluoro-2-indolyl des-chlorohalopemide) and PDE4 inhibition with rolipram abrogated both the anti-tumoral and endocytic effects of PAP inhibition. Prolonged treatments with a low concentration of PAP inhibitors, although without detectable endocytic effects, still counteracted cell proliferation, induced apoptosis and decreased anchorage-independent growth of cells bearing EGFR oncogenic influences. Overall, our results show that PAP inhibitors can counteract EGFR oncogenic traits, including receptor overexpression or activating mutations resistant to current tyrosine kinase inhibitors, perturbing EGFR endocytic trafficking and perhaps other as yet unknown processes, depending on treatment conditions. This puts PAP activity forward as a new suitable target against EGFR-driven malignancy. PMID:24597955

  8. Effects of ferulic acid and some of its microbial metabolic products on radicle growth of cucumber.

    PubMed

    Blum, U; Dalton, B R; Rawlings, J O

    1984-08-01

    An initial survey of the effects of aqueous solutions of ferulic acid and three of its microbial metabolic products at pH 4.5, 6.0, and 7.5 was determined on radicle growth of 11 crop species in Petri dishes. These bioassays indicated that cucumber, ladino clover, lettuce, mung bean, and wheat were inhibited by ferulic, caffeic, protocatechuic, and/or vanillic acids and that the magnitude of inhibition varied with concentration (0-2 mM), phenolic acid, and pH of the initial solution. The pH values of the initial solutions changed considerably when added to the Petri dishes containing filter paper and seeds. The final pH values after 48 hr were 6.6, 6.8, and 7.1, respectively, for the initial 4.5, 6.0, and 7.5 pH solutions. The amounts of the phenolic acids in the Petri dishes declined rapidly over the 48 hr of the bioassay, and the rate of phenolic acid decline was species specific. Cucumber was subsequently chosen as the bioassay species for further study. MES buffer was used to stabilize the pH of the phenolic acid solutions which ranged between 5.5 and 5.8 for all subsequent studies. Inhibition of radicle growth declined in a curvilinear manner over the 0-2 mM concentration range. At 0.125 and 0.25 mM concentrations of ferulic acid, radicle growth of cucumber was inhibited 7 and 14%, respectively. A variety of microbial metabolic products of ferulic acid was identified in the Petri dishes and tested for toxicity. Only vanillic acid was as inhibitory as ferulic acid. The remaining phenolic acids were less inhibitory to noninhibitory. When mixtures of phenolic acids were tested, individual components were antagonistic to each other in the inhibition of cucumber radicle growth. Depending on the initial total concentration of the mixture, effects ranged from 5 to 35% lower than the sum of the inhibition of each phenolic acid tested separately. Implications of these findings to germination bioassays are discussed. PMID:24318904

  9. Modified Lactic Acid Bacteria Detect and Inhibit Multiresistant Enterococci

    PubMed Central

    2015-01-01

    We designed Lactococcus lactis to detect Enterococcus faecalis. Upon detection, L. lactis produce and secrete antienterococcal peptides. The peptides inhibit enterococcal growth and reduce viability of enterococci in the vicinity of L. lactis. The enterococcal sex pheromone cCF10 serves as the signal for detection. Expression vectors derived from pCF10, a cCF10-responsive E. faecalis sex-pheromone conjugative plasmid, were engineered in L. lactis for the detection system. Recombinant host strains were engineered to express genes for three bacteriocins, enterocin A, hiracin JM79 and enterocin P, each with potent antimicrobial activity against E. faecalis. Sensitive detection and specific inhibition occur both in agar and liquid media. The engineered L. lactis also inhibited growth of multidrug-resistant E. faecium strains, when induced by cCF10. The presented vectors and strains can be components of a toolbox for the development of alternative antibiotic technologies targeting enterococci at the site of infection. PMID:24896372

  10. Fenretinide inhibits myeloma cell growth, osteoclastogenesis and osteoclast viability

    PubMed Central

    Li, Xin; Ling, Wen; Pennisi, Angela; Khan, Sharmin; Yaccoby, Shmuel

    2009-01-01

    Fenretinide (4HPR), a nontoxic analog of ATRA, has been investigated in various malignancies but not in multiple myeloma (MM), a plasma cell malignancy associated with induction of osteolytic bone disease. Here we show that 4HPR induces apoptosis through increased level of ROS and activation of caspase-8, 9 and 3, and inhibits growth of several MM cell lines in a dose-dependent manner. Serum or co-culture with the supportive osteoclasts partially protects MM cells from 4HPR-induced growth inhibition. Sphingosine-1 phosphate (S1P) significantly protects MM cells from 4HPR-induced apoptosis suggesting that as in other malignancies, this drug up-regulates ceramide in MM cells. 4HPR has no toxic effects on non-malignant cells such as blood mononucleated cells, mesenchymal stem cells and osteoblasts, but markedly reduces viability of endothelial cells and mature osteoclasts and inhibits differentiation of osteoclasts and MM-induced tube formation. 4HPR is a potential anti-MM agent, affecting MM cells and MM-induced bone disease and angiogenesis. PMID:19446953

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

    PubMed

    Lin, Daohui; Xing, Baoshan

    2007-11-01

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

  12. Growth temperature affects accumulation of exogenous fatty acids and fatty acid composition in Schizosaccharomyces pombe

    Microsoft Academic Search

    Virginia M. McDonough; Therese M. Roth

    2004-01-01

    The incorporation of exogenously supplied fatty acids, palmitic acid, palmitoleic acid, oleic acid and linoleic acid, was\\u000a examined in the yeast Schizosaccharomyces pombe at two growth temperatures, 20?C and 30?C. Fatty acids supplied to S. pombe in the growth medium were found to be preferentially incorporated into the cells, becoming a dominant species. The relative\\u000a increase in exogenous fatty acids

  13. A cortical astrocyte subpopulation inhibits axon growth in vitro and in vivo

    PubMed Central

    LIU, RUI; WANG, ZHE; GOU, LIN; XU, HANPENG

    2015-01-01

    Astrocytes are the most heterogeneous and predominant glial cell type in the central nervous system. However, the functional significance of this heterogeneity remains to be elucidated. Following injury, damaged astrocytes inhibit axonal regeneration in vivo and in vitro. Cultured primary astrocytes are commonly considered good supportive substrates for neuron attachment and axon regeneration. However, it is not known whether different populations of cells in the heterogeneous astrocyte culture affect neuron behavior in the same way. In the present study, the effect of astrocyte heterogeneity on neuronal attachment and neurite outgrowth was examined using an in vitro and in vivo co-culture system. In vitro, neonatal cortical astrocytes were co-cultured with purified dorsal root ganglia (DRG) neurons and astrocyte growth morphology, neuron attachment and neurite growth were evaluated. The results demonstrated that the heterogeneous astrocyte cells showed two different types of growth pattern, typical and atypical. Typical astrocytes were supportive to neuron attachment and neurite growth, which was consistent with previous studies, whereas atypical astrocytes inhibited neuron attachment and neurite growth. These inhibitory astrocytes exhibited a special growth pattern with various shapes and sizes, a high cell density, few oligodendrocytes on the top layer and occupied a smaller growth area compared with typical astrocytes. Neurites extended freely on typical supportive astrocyte populations, however, moved away when they reached atypical astrocyte growth pattern. Neurons growing on the atypical astrocyte pattern demonstrated minimal neurite outgrowth and these neurites had a dystrophic appearance, however, neuronal survival was unaffected. Immunocytochemistry studies demonstrated that these atypical inhibitory astrocytes were glial fibrillary acidic protein (GFAP) positive cells. The existence of inhibitory astrocyte subpopulations in normal astrocytes reflects the complexity of the function of astrocyte populations. In vivo, DRG neurons in grey matter did not show neurite growth, while DRG neurons survived and showed robust axon outgrowth along the corpus callosum. In conclusion, further studies on this new type of inhibitory astrocyte subpopulation may deepen our understanding of the complex biology of astrocytes. PMID:25936767

  14. Inhibition of C4 photosynthesis by (benzamidooxy)acetic acid.

    PubMed

    Nakamoto, H; Ku, M S; Edwards, G E

    1982-12-01

    (Benzamidooxy)acetic acid (common name benzadox) which has herbicidal properties was evaluated as a potential inhibitor of photosynthesis in C4 plants. Among enzymes of the C4 pathway, it was a relatively strong inhibitor of alanine aminotransferase in in vitro experiments at concentrations of 5mM. In benzadox treated leaves of Panicum miliaceum, a NAD-malic enzyme type C4 species, there was strong inhibition of both alanine and aspartate aminotransferase and of photosynthetic O2 evolution within one hour. Consistent with the inhibition of these enzymes of the C4 cycle, the pool sizes of metabolites of the cycle was altered: the aspartate level was increased two fold, while the levels of other metabolites such as pyruvate, alanine, oxalacetate and malate were decreased. Kinetic studies with partially purified alanine aminotransferase showed that benzadox is a competitive inhibitor with respect to alanine and a noncompetitive inhibitor with respect to 2-oxoglutarate. Comparisons between the structures and inhibitory actions of benzadox and (aminooxy)acetic acid, the latter a potent inhibitor of alanine and aspartate aminotransferases, suggest that in vivo, benzadox may exert its effect through metabolism to (aminooxy)acetic acid. PMID:24458342

  15. Inhibition of Flowering in Hyoscyamus niger by 6Azauracil without Suppression of Stem Growth

    Microsoft Academic Search

    F. Seidlová; J. Krekule; L. Teltscherová

    1967-01-01

    IN Hyoscyamus niger the uracil analogue 6-azauracil has partially inhibited photoperiodic induction and caused malformations of young leaves, but these phenomena were not associated with an inhibition of stem growth. Application of pyrimidine analogues usually causes an inhibition of growth processes which involve cell division2-4 as well as cell elongation5,6. Inhibition can cause abnormal growth of the cells, thus leading

  16. Transient self-inhibition of the growth of Lactobacillus delbrueckii subsp. bulgaricus in a pH-regulated fermentor.

    PubMed

    Mercade, Myriam; Duperray, Florence; Loubière, Pascal

    2003-10-01

    An industrial strain of Lactobacillus delbrueckii subsp. bulgaricus was grown in a synthetic medium on lactose as carbon substrate, in a pH-regulated fermentor. Growth proceeded in two distinct phases separated by a transient stationary phase. Various experimental approaches were used to identify the cause of this growth arrest. Growth experiments in L. bulgaricus culture supernatant fluids collected at different cultivation times in fermentor, and supplemented or not with various nutritional solutions, enabled us to discard the possibility of a nutritional limitation. Tube cultures of L. bulgaricus in medium supplemented with various lactic acid concentrations showed a potential inhibition by this metabolic end product but confirmed that this inhibition was not responsible for the cessation of growth. It was concluded that at least one inhibitory compound was produced during the growth phase of the strain, and this compound disappeared from the medium in the transient stationary phase, enabling the growth to start again later in the culture. Indeed, the stoichiometric analysis of the culture showed, firstly, that unidentified carbon compounds were produced from lactose during growth, which were probably converted in lactic acid during the transient stationary phase and, secondly, that part of the amino acids consumed gave catabolic end products. Finally, bacteriocin-like compounds were not considered to be responsible for this growth arrest. PMID:12910546

  17. RNA aptamers inhibit the growth of the fish pathogen viral hemorrhagic septicemia virus (VHSV).

    PubMed

    Punnarak, Porntep; Santos, Mudjekeewis D; Hwang, Seong Don; Kondo, Hidehiro; Hirono, Ikuo; Kikuchi, Yo; Aoki, Takashi

    2012-12-01

    Viral hemorrhagic septicemia virus (VHSV) is a serious disease impacting wild and cultured fish worldwide. Hence, an effective therapeutic method against VHSV infection needs to be developed. Aptamer technology is a new and promising method for diagnostics and therapeutics. It revolves around the use of an aptamer molecule, an artificial ligand (nucleic acid or protein), which has the capacity to recognize target molecules with high affinity and specificity. Here, we aimed at selecting RNA aptamers that can specifically bind to and inhibit the growth of a strain of fish VHSV both in vitro and in vivo. Three VHSV-specific RNA aptamers (F1, F2, and C6) were selected from a pool of artificially and randomly produced oligonucleotides using systematic evolution of ligands by exponential enrichment. The three RNA aptamers showed obvious binding to VHSV in an electrophoretic mobility shift assay but not to other tested viruses. The RNA aptamers were tested for their ability to inhibit VHSV in vitro using hirame natural embryo (HINAE) cells. Cytopathic effect and plaque assays showed that all aptamers inhibited the growth of VHSV in HINAE cells. In vivo tests using RNA aptamers produced by Rhodovulum sulfidophilum showed that extracellular RNA aptamers inhibited VHSV infection in Japanese flounder. These results suggest that the RNA aptamers are a useful tool for protection against VHSV infection in Japanese flounder. PMID:22527269

  18. Effects of ferulic acid and some of its microbial metabolic products on radicle growth of cucumber

    Microsoft Academic Search

    Udo Blum; Barry R. Dalton; John O. Rawlings

    1984-01-01

    An initial survey of the effects of aqueous solutions of ferulic acid and three of its microbial metabolic products at pH 4.5, 6.0, and 7.5 was determined on radicle growth of 11 crop species in Petri dishes. These bioassays indicated that cucumber, ladino clover, lettuce, mung bean, and wheat were inhibited by ferulic, caffeic, protocatechuic, and\\/or vanillic acids and that

  19. Growth of Thiobacillus ferrooxidans on Formic Acid.

    PubMed

    Pronk, J T; Meijer, W M; Hazeu, W; van Dijken, J P; Bos, P; Kuenen, J G

    1991-07-01

    A variety of acidophilic microorganisms were shown to be capable of oxidizing formate. These included Thiobacillus ferrooxidans ATCC 21834, which, however, could not grow on formate in normal batch cultures. However, the organism could be grown on formate when the substrate supply was growth limiting, e.g., in formate-limited chemostat cultures. The cell densities achieved by the use of the latter cultivation method were higher than cell densities reported for growth of T. ferrooxidans on ferrous iron or reduced sulfur compounds. Inhibition of formate oxidation by cell suspensions, but not cell extracts, of formate-grown T. ferrooxidans occurred at formate concentrations above 100 muM. This observation explains the inability of the organism to grow on formate in batch cultures. Cells grown in formate-limited chemostat cultures retained the ability to oxidize ferrous iron at high rates. Ribulose 1,5-bisphosphate carboxylase activities in cell extracts indicated that T. ferrooxidans employs the Calvin cycle for carbon assimilation during growth on formate. Oxidation of formate by cell extracts was NAD(P) independent. PMID:16348525

  20. Growth of Thiobacillus ferrooxidans on Formic Acid

    PubMed Central

    Pronk, J. T.; Meijer, W. M.; Hazeu, W.; van Dijken, J. P.; Bos, P.; Kuenen, J. G.

    1991-01-01

    A variety of acidophilic microorganisms were shown to be capable of oxidizing formate. These included Thiobacillus ferrooxidans ATCC 21834, which, however, could not grow on formate in normal batch cultures. However, the organism could be grown on formate when the substrate supply was growth limiting, e.g., in formate-limited chemostat cultures. The cell densities achieved by the use of the latter cultivation method were higher than cell densities reported for growth of T. ferrooxidans on ferrous iron or reduced sulfur compounds. Inhibition of formate oxidation by cell suspensions, but not cell extracts, of formate-grown T. ferrooxidans occurred at formate concentrations above 100 ?M. This observation explains the inability of the organism to grow on formate in batch cultures. Cells grown in formate-limited chemostat cultures retained the ability to oxidize ferrous iron at high rates. Ribulose 1,5-bisphosphate carboxylase activities in cell extracts indicated that T. ferrooxidans employs the Calvin cycle for carbon assimilation during growth on formate. Oxidation of formate by cell extracts was NAD(P) independent. PMID:16348525

  1. Insulin-like growth factors modulate the growth inhibitory effects of retinoic acid on MCF-7 breast cancer cells.

    PubMed

    Bentel, J M; Lebwohl, D E; Cullen, K J; Rubin, M S; Rosen, N; Mendelsohn, J; Miller, W H

    1995-10-01

    Retinoids are currently being tested for the treatment and prevention of several human cancers, including breast cancer. However, the anti-cancer and growth inhibitory mechanisms of retinoids are not well understood. All-trans retinoic acid (RA) inhibits the growth of the estrogen receptor-positive (ER+) breast cancer cell line, MCF-7, in a reversible and dose-dependent manner. In contrast, insulin-like growth factors (IGF-I, IGF-II) and insulin are potent stimulators of the proliferation of MCF-7 and several other breast cancer cell lines. Pharmacologic doses of RA (> or = 10(-6) M) completely inhibit IGF-I-stimulated MCF-7 cell growth. Published data suggest that the growth inhibitory action of RA on IGF-stimulated cell growth is linear and dose-dependent, similar to RA inhibition of unstimulated or estradiol-stimulated MCF-7 cell growth. Surprisingly, we have found that IGF-I or insulin-stimulated cell growth is increased to a maximum of 132% and 127%, respectively, by cotreatment with 10(-7) M RA, and that 10(-9) - 10(-7) M RA increase cell proliferation compared to IGF-I or insulin alone. MCF-7 cells that stably overexpress IGF-II are also resistant to the growth inhibitory effects of 10(-9) - 10(-7) M RA. Treatment with the IGF-I receptor blocking antibody, alpha IR-3, restores RA-induced growth inhibition of IGF-I-treated or IGF-II-overexpressing MCF-7 cells, indicating that the IGF-I receptor is mediating these effects. IGFs cannot reverse all RA effects since the altered cell culture morphology of RA-treated cells is similar in growth-inhibited cultures and in IGF-II expressing clones that are resistant to RA-induced growth inhibition. These results indicate that RA action on MCF-7 cells is biphasic in the presence of IGF-I or insulin with 10(-9) - 10(-7) M RA enhancing cell proliferation and > or = 10(-6) M RA causing growth inhibition. As IGF-I and IGF-II ligands are frequently detectable in breast tumor tissues, their potential for modulation of RA effects should be considered when evaluating retinoids for use in in vivo experimental studies and for clinical purposes. Additionally, the therapeutic use of inhibitors of IGF action in combination with RA is suggested by these studies. PMID:7559803

  2. ?-Pinene Inhibits Growth and Induces Oxidative Stress in Roots

    PubMed Central

    SINGH, HARMINDER P.; BATISH, DAIZY R.; KAUR, SHALINDER; ARORA, KOMAL; KOHLI, RAVINDER K.

    2006-01-01

    • Background and Aims Determining the mode of action of allelochemicals is one of the challenging aspects in allelopathic studies. Recently, allelochemicals have been proposed to cause oxidative stress in target tissue and induce an antioxidant mechanism. ?-Pinene, one of the common monoterpenoids emitted from several aromatic plants including forest trees, is known for its growth-inhibitory activity. However, its mechanism of action remains unexplored. The aim of the present study was to determine the inhibitory effect of ?-pinene on root growth and generation of reactive oxygen species, as indicators of oxidative stress and changes in activities of antioxidant enzymes. • Methods Effects of ?-pinene on early root growth were studied in five test species, Cassia occidentalis, Amaranthus viridis, Triticum aestivum, Pisum sativum and Cicer arietinum. Electrolyte leakage, lipid peroxidation, hydrogen peroxide generation, proline accumulation, and activities of the enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT) and glutathione reductase (GR) were studied in roots of C. occidentalis. • Key Results ?-Pinene inhibited the radicle growth of all the test species. Exposure of C. occidentalis roots to ?-pinene enhanced solute leakage, and increased levels of malondialdehyde, proline and hydrogen peroxide, indicating lipid peroxidation and induction of oxidative stress. Activities of the antioxidant enzymes SOD, CAT, GPX, APX and GR were significantly elevated, thereby indicating the enhanced generation of reactive oxygen species (ROS) upon ?-pinene exposure. Increased levels of scavenging enzymes indicates their induction as a secondary defence mechanism in response to ?-pinene. • Conclusions It is concluded that ?-pinene inhibits early root growth and causes oxidative damage in root tissue through enhanced generation of ROS, as indicated by increased lipid peroxidation, disruption of membrane integrity and elevated antioxidant enzyme levels. PMID:17028297

  3. Synergistic inhibition of corrosion of steel in sulfuric acid solutions

    SciTech Connect

    Gordeeva, I.I.; Efimov, I.V.; Legin, G.Y.

    1985-07-01

    The authors have studied synergism in compositions of sodium chloride with simple aliphatic compounds containing the neutral phosphate AF-1, the neutral phosphonate AF-10, and the trialkylphosphine oxide AF-13. In contrast with the amines, all the substances have extremely low basicity and are almost incapable of forming cations in an acidic medium. The substances exhibit marked synergism with chloride ions. For comparison, the authors caused the inhibition of steel Stl with carbonyl compounds similar in structure to the three substances, namely diethyl carbonate, butyl acetate, and 2-octanone. The carbonyl compounds are weaker inhibitors, but in compositions with sodium chloride, their qualitative effects are similar to those of phosphoryl compounds.

  4. Positional isomers of aspirin are equally potent in inhibiting colon cancer cell growth: differences in mode of cyclooxygenase inhibition.

    PubMed

    Kodela, Ravinder; Chattopadhyay, Mitali; Goswami, Satindra; Gan, Zong Yuan; Rao, Praveen P N; Nia, Kamran V; Velázquez-Martínez, Carlos A; Kashfi, Khosrow

    2013-04-01

    We compared the differential effects of positional isomers of acetylsalicylic acid (o-ASA, m-ASA, and p-ASA) on cyclooxygenase (COX) inhibition, gastric prostaglandin E2 (PGE2), malondialdehyde, tumor necrosis factor-alpha (TNF-?) levels, superoxide dismutase (SOD) activity, human adenocarcinoma colon cancer cell growth inhibition, cell proliferation, apoptosis, and cell-cycle progression. We also evaluated the gastric toxicity exerted by ASA isomers. All ASA isomers inhibit COX enzymes, but only the o-ASA exerted an irreversible inhibitory profile. We did not observe a significant difference between ASA isomers in their ability to decrease the in vivo synthesis of PGE2 and SOD activity. Furthermore, all isomers increased the levels of gastric and TNF-? when administered orally at equimolar doses. We observed a dose-dependent cell growth inhibitory effect; the order of potency was p-ASA > m-ASA ? o-ASA. There was a dose-dependent decrease in cell proliferation and an increase in apoptosis, with a concomitant Go/G1 arrest. The ulcerogenic profile of the three ASA isomers showed a significant difference between o-ASA (aspirin) and its two positional isomers when administered orally at equimolar doses (1 mmol/kg); the ulcer index (UI) for o-ASA indicated extensive mucosal injury (UI = 38), whereas m-ASA and p-ASA produced a significantly decreased toxic response (UI = 12 and 8, respectively) under the same experimental conditions. These results suggest that the three positional isomers of ASA exert practically the same biologic profile in vitro and in vivo but showed different safety profiles. The mechanism of gastric ulcer formation exerted by aspirin and its two isomers warrants a more detailed and thorough investigation. PMID:23349335

  5. Boric Acid Inhibits Germination and Colonization of Saprolegnia Spores In Vitro and In Vivo

    PubMed Central

    Ali, Shimaa E.; Thoen, Even; Evensen, Øystein; Skaar, Ida

    2014-01-01

    Saprolegnia infections cause severe economic losses among freshwater fish and their eggs. The banning of malachite green increased the demand for finding effective alternative treatments to control the disease. In the present study, we investigated the ability of boric acid to control saprolegniosis in salmon eggs and yolk sac fry. Under in vitro conditions, boric acid was able to decrease Saprolegnia spore activity and mycelial growth in all tested concentrations above 0.2 g/L, while complete inhibition of germination and growth was observed at a concentration of 0.8 g/L. In in vivo experiments using Atlantic salmon eyed eggs, saprolegniosis was controlled by boric acid at concentrations ranging from 0.2–1.4 g/L during continuous exposure, and at 1.0–4.0 g/L during intermittent exposure. The same effect was observed on salmon yolk sac fry exposed continuously to 0.5 g/L boric acid during the natural outbreak of saprolegniosis. During the experiments no negative impact with regard to hatchability and viability was observed in either eggs or fry, which indicate safety of use at all tested concentrations. The high hatchability and survival rates recorded following the in vivo testing suggest that boric acid is a candidate for prophylaxis and control of saprolegniosis. PMID:24699283

  6. Effect of Dietary Acid or Aluminum on Growth and Growth-Related Hormones in Young Chickens

    Microsoft Academic Search

    M. C. Capdevielle; C. G. Scanes

    1995-01-01

    The effect of two concentrations of dietary acid (sulfuric acid) or aluminum (aluminum sulfate) on growth and growth-related hormones was examined in a heavy (broiler) strain of chicken between 4 and 18 days old. Growth (body weight, average daily gain, and tibial length) in chicks receiving either dietary acid or aluminum-containing diets were compared to chicks fed a control diet

  7. Minocycline inhibits the production of the precursor form of nerve growth factor by retinal microglial cells?

    PubMed Central

    Yang, Xiaochun; Duan, Xuanchu

    2013-01-01

    A rat model of acute ocular hypertension was established by enhancing the perfusion of balanced salt solution in the anterior chamber of the right eye. Minocycline (90 mg/kg) was administered intraperitoneally into rats immediately after the operation for 3 consecutive days. Immunofluorescence, western blot assay and PCR detection revealed that the expression of the precursor form of nerve growth factor, nerve growth factor and the p75 neurotrophin receptor, and the mRNA expression of nerve growth factor and the p75 neurotrophin receptor, increased after acute ocular hypertension. The number of double-labeled CD11B- and precursor form of nerve growth factor-positive cells, glial fibrillary acidic protein- and p75 neurotrophin receptor-positive cells, glial fibrillary acidic protein- and caspase-3-positive cells in the retina markedly increased after acute ocular hypertension. The above-described expression decreased after minocycline treatment. These results suggested that minocycline inhibited the increased expression of the precursor form of nerve growth factor in microglia, the p75 neurotrophin receptor in astroglia, and protected cells from apoptosis. PMID:25206672

  8. Inhibition of neutrophil elastase activity by cinnamic acid derivatives from Cimicifuga racemosa.

    PubMed

    Löser, B; Kruse, S O; Melzig, M F; Nahrstedt, A

    2000-12-01

    Caffeic acid, fukinolic acid as well as cimicifugic acids A, B, E and F isolated from the rhizomes of Cimicifuga racemosa (Ranunculaceae) inhibited the activity of neutrophil elastase (EC 3.4.21.37) in a dose-dependent manner. An IC50 of 93 mumol/L was determined for caffeic acid and 0.23 mumol/L for fukinolic acid. Cimicifugic acid A inhibited the enzyme with an IC50 of 2.2 mumol/L, cimicifugic acid B with 11.4 mumol/L, and cimicifugic acid F with 18 mumol/L. Cimicifugic acid E was only a very weak inhibitor. PMID:11199135

  9. Drugs which inhibit osteoclast function suppress tumor growth through calcium reduction in bone.

    PubMed

    Li, Xin; Liao, Jinhui; Park, Serk In; Koh, Amy J; Sadler, William D; Pienta, Kenneth J; Rosol, Thomas J; McCauley, Laurie K

    2011-06-01

    Prostate carcinoma frequently metastasizes to bone where the microenvironment facilitates its growth. Inhibition of bone resorption is effective in reducing tumor burden and bone destruction in prostate cancer. However, whether drugs that inhibit osteoclast function inhibit tumor growth independent of inhibition of bone resorption is unclear. Calcium is released during bone resorption and the calcium sensing receptor is an important regulator of cancer cell proliferation. The goal of this investigation was to elucidate the role of calcium released during bone resorption and to determine the impact of drugs which suppress bone resorption on tumor growth in bone. To compare tumor growth in a skeletal versus non-skeletal site, equal numbers of canine prostate cancer cells expressing luciferase (ACE-1(luc)) were inoculated into a simple collagen matrix, neonatal mouse vertebrae (vossicles), human de-proteinized bone, or a mineralized collagen matrix. Implants were placed subcutaneously into athymic mice. Luciferase activity was used to track tumor growth weekly, and at one month tumors were dissected for histologic analysis. Luciferase activity and tumor size were greater in vossicles, de-proteinized bone and mineralized collagen matrix versus non-mineralized collagen implants. The human osteoblastic prostate carcinoma cell line C4-2b also grew better in a mineral rich environment with a greater proliferation of C4-2b cells reflected by Ki-67 staining. Zoledronic acid (ZA), a bisphosphonate, and recombinant OPG-Fc, a RANKL inhibitor, were administered to mice bearing vertebral implants (vossicles) containing ACE-1 osteoblastic prostate cancer cells. Vossicles or collagen matrices were seeded with ACE-1(luc) cells subcutaneously in athymic mice (2 vossicles, 2 collagen implants/mouse). Mice received ZA (5 ?g/mouse, twice/week), (OPG-Fc at 10mg/kg, 3 times/week) or vehicle, and luciferase activity was measured weekly. Histologic analysis of the tumors, vossicles and endogenous bones and serum biochemistry were performed. Antiresorptive administration was associated with decreased serum TRAP5b, reduced osteoclast numbers, and increased tibia and vossicle bone areas. ZA significantly decreased bone marrow calcium concentrations without affecting serum calcium. ZA and OPG-Fc significantly inhibited tumor growth in bone but not in collagen implants. In conclusion, the inhibitory effects of ZA or OPG-Fc on prostate tumor growth in bone are mediated via blocking bone resorption and calcium release from bone. PMID:21419883

  10. Drugs Which Inhibit Osteoclast Function Suppress Tumor Growth through Calcium Reduction in Bone

    PubMed Central

    Li, Xin; Liao, Jinhui; Park, Serk In; Koh, Amy J; Sadler, William D; Pienta, Kenneth J; Rosol, Thomas J; McCauley, Laurie K

    2011-01-01

    Prostate carcinoma frequently metastasizes to bone where the microenvironment facilitates its growth. Inhibition of bone resorption is effective in reducing tumor burden and bone destruction in prostate cancer. However, whether drugs that inhibit osteoclast function inhibit tumor growth independent of inhibition of bone resorption is unclear. Calcium is released during bone resorption and the calcium sensing receptor is an important regulator of cancer cell proliferation. The goal of this investigation was to elucidate the role of calcium released during bone resorption and to determine the impact of drugs which suppress bone resorption on tumor growth in bone. To compare tumor growth in a skeletal versus non-skeletal site, equal numbers of canine prostate cancer cells expressing luciferase (ACE-1luc) prostate cancer cells were inoculated into a simple collagen matrix, neonatal mouse vertebrae (vossicles), human de-proteinized bone, or a mineralized collagen matrix. Implants were placed subcutaneously into athymic mice. Luciferase activity was used to track tumor growth weekly and at one month tumors were dissected for histologic analysis. Luciferase activity and tumor size were greater in vossicles, de-proteinized bone and mineralized collagen matrix versus non-mineralized collagen implants. The human osteoblastic prostate carcinoma cell line C4-2b also grew better in a mineral rich environment with a greater proliferation of C4-2b cells reflected by Ki-67 staining. Zoledronic acid (ZA), a bisphosphonate, and recombinant OPG-Fc, a RANKL inhibitor, were administered to mice bearing vertebral implants (vossicles) containing ACE-1 osteoblastic prostate cancer cells. Vossicles or collagen matrices were seeded with ACE-1luc cells subcutaneously in athymic mice (2 vossicles, 2 collagen implants/mouse). Mice received ZA (5?g/mouse, twice/week), (OPG-Fc at 10mg/kg, 3 times/week) or vehicle, and luciferase activity was measured weekly. Histologic analysis of the tumors, vossicles and endogenous bones and serum biochemistry were performed. Antiresorptive administration was associated with decreased serum TRAP5b and reduced osteoclast numbers, increased tibia and vossicle bone areas. ZA significantly decreased bone marrow calcium concentrations without affecting serum calcium. ZA and OPG-Fc significantly inhibited tumor growth in bone but not in collagen implants. In conclusion, the inhibitory effects of ZA or OPG-Fc on prostate tumor growth in bone are mediated via blocking bone resorption and calcium release from bone. PMID:21419883

  11. Kinetic-spectrophotometric determination of ascorbic acid by inhibition of the hydrochloric acid-bromate reaction

    NASA Astrophysics Data System (ADS)

    Ensafi, Ali A.; Rezaei, B.; Movahedinia, H.

    2002-10-01

    A new analytical method was developed for the determination of ascorbic acid in fruit juice and pharmaceuticals. The method is based on its inhibition effect on the reaction between hydrochloric acid and bromate. The decolourisation of Methyl Orange by the reaction products was used to monitor the reaction spectrophotometrically at 510 nm. The linearity range of the calibration graph depends on bromate concentration. The variable affecting the rate of the reaction was investigated. The method is simple, rapid, relatively sensitive and precise. The limit of detection is 7.6×10 -6 M and calibration rang is 8×10 -6-1.2×10 -3 M ascorbic acid. The relative standard deviation of seven replication determinations of 8×10 -6 and 2×10 -5 M ascorbic acid was 2.8 and 1.7%, respectively. The influence of potential interfering substance was studied. The method was successfully applied for the determination of ascorbic acid in pharmaceuticals.

  12. FH535 Inhibited Migration and Growth of Breast Cancer Cells

    PubMed Central

    Iida, Joji; Dorchak, Jesse; Lehman, John R.; Clancy, Rebecca; Luo, Chunqing; Chen, Yaqin; Somiari, Stella; Ellsworth, Rachel E.; Hu, Hai; Mural, Richard J.; Shriver, Craig D.

    2012-01-01

    There is substantial evidence indicating that the WNT signaling pathway is activated in various cancer cell types including breast cancer. Previous studies reported that FH535, a small molecule inhibitor of the WNT signaling pathway, decreased growth of cancer cells but not normal fibroblasts, suggesting this pathway plays a role in tumor progression and metastasis. In this study, we tested FH535 as a potential inhibitor for malignant phenotypes of breast cancer cells including migration, invasion, and growth. FH535 significantly inhibited growth, migration, and invasion of triple negative (TN) breast cancer cell lines (MDA-MB231 and HCC38) in vitro. We demonstrate that FH535 was a potent growth inhibitor for TN breast cancer cell lines (HCC38 and MDA-MB-231) but not for other, non-TN breast cancer cell lines (MCF-7, T47D or SK-Br3) when cultured in three dimensional (3D) type I collagen gels. Western blotting analyses suggest that treatment of MDA-MB-231 cells with FH535 markedly inhibited the expression of NEDD9 but not activations of FAK, Src, or downstream targets such as p38 and Erk1/2. We demonstrated that NEDD9 was specifically associated with CSPG4 but not with ?1 integrin or CD44 in MDA-MB-231 cells. Analyses of gene expression profiles in breast cancer tissues suggest that CSPG4 expression is higher in Basal-type breast cancers, many of which are TN, than any other subtypes. These results suggest not only a mechanism for migration and invasion involving the canonical WNT-signaling pathways but also novel strategies for treating patients who develop TN breast cancer. PMID:22984505

  13. Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the VEGFR2/Src/FAK Pathway.

    PubMed

    Ku, Chung-Yu; Wang, Ying-Ren; Lin, Hsuan-Yuan; Lu, Shao-Chun; Lin, Jung-Yaw

    2015-01-01

    Inhibition of VEGFR2 activity has been proposed as an important strategy for the clinical treatment of hepatocellular carcinoma (HCC). In this study, we identified corosolic acid (CA), which exists in the root of Actinidia chinensis, as having a significant anti-cancer effect on HCC cells. We found that CA inhibits VEGFR2 kinase activity by directly interacting with the ATP binding pocket. CA down-regulates the VEGFR2/Src/FAK/cdc42 axis, subsequently decreasing F-actin formation and migratory activity in vitro. In an in vivo model, CA exhibited an effective dose (5 mg/kg/day) on tumor growth. We further demonstrate that CA has a synergistic effect with sorafenib within a wide range of concentrations. In conclusion, this research elucidates the effects and molecular mechanism for CA on HCC cells and suggests that CA could be a therapeutic or adjuvant strategy for patients with aggressive HCC. PMID:25978354

  14. Corosolic Acid Inhibits Hepatocellular Carcinoma Cell Migration by Targeting the VEGFR2/Src/FAK Pathway

    PubMed Central

    Ku, Chung-Yu; Wang, Ying-Ren; Lin, Hsuan-Yuan; Lu, Shao-Chun; Lin, Jung-Yaw

    2015-01-01

    Inhibition of VEGFR2 activity has been proposed as an important strategy for the clinical treatment of hepatocellular carcinoma (HCC). In this study, we identified corosolic acid (CA), which exists in the root of Actinidia chinensis, as having a significant anti-cancer effect on HCC cells. We found that CA inhibits VEGFR2 kinase activity by directly interacting with the ATP binding pocket. CA down-regulates the VEGFR2/Src/FAK/cdc42 axis, subsequently decreasing F-actin formation and migratory activity in vitro. In an in vivo model, CA exhibited an effective dose (5 mg/kg/day) on tumor growth. We further demonstrate that CA has a synergistic effect with sorafenib within a wide range of concentrations. In conclusion, this research elucidates the effects and molecular mechanism for CA on HCC cells and suggests that CA could be a therapeutic or adjuvant strategy for patients with aggressive HCC. PMID:25978354

  15. Upregulation of GRIM?19 inhibits the growth and invasion of human breast cancer cells.

    PubMed

    Zhang, Wei; Du, Ye; Jiang, Tong; Geng, Wei; Yuan, Jiuli; Zhang, Duo

    2015-08-01

    Gene associated with retinoid?interferon (IFN)?induced mortality 19 (GRIM?19), a novel IFN??/retinoic acid?inducible gene product, has been identified as a potential tumor suppressor, which is associated with the inhibition of tumor growth. GRIM?19 has been demonstrated to be downregulated in the ovarian tissue of patients with breast cancer, however, its role in breast cancer remains to be fully elucidated. In the present study, a recombinant eukaryotic expression plasmid carrying GRIM?19 was constructed and then transfected into the MCF7 human breast cancer cell line to examine its effects on breast cancer cell growth, migration and invasion using several in vitro approaches. The results demonstrated that upregulation GRIM?19 in the MCF7 cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell apoptosis. Additionally, upregulation of GRIM?19 also suppressed the secretion of urokinase?type plasminogen activator (u?PA), matrix metalloproteinase (MMP)?2, MMP?9 and vascular endothelial growth factor (VEGF). It was also demonstrated that the activation of signal transducer and activator of transcription 3 (STAT3) was downregulated by the expression of GRIM?19. These results revealed that overexpression of the GRIM?19 gene may be an effective approach to control the growth and invasion of human breast cancer cells. PMID:25955394

  16. Dynamic Light Scattering Study of Inhibition of Nucleation and Growth of Hydroxyapatite Crystals by Osteopontin

    PubMed Central

    de Bruyn, John R.; Goiko, Maria; Mozaffari, Maryam; Bator, Daniel; Dauphinee, Ron L.; Liao, Yinyin; Flemming, Roberta L.; Bramble, Michael S.; Hunter, Graeme K.; Goldberg, Harvey A.

    2013-01-01

    We study the effect of isoforms of osteopontin (OPN) on the nucleation and growth of crystals from a supersaturated solution of calcium and phosphate ions. Dynamic light scattering is used to monitor the size of the precipitating particles and to provide information about their concentration. At the ion concentrations studied, immediate precipitation was observed in control experiments with no osteopontin in the solution, and the size of the precipitating particles increased steadily with time. The precipitate was identified as hydroxyapatite by X-ray diffraction. Addition of native osteopontin (nOPN) extracted from rat bone caused a delay in the onset of precipitation and reduced the number of particles that formed, but the few particles that did form grew to a larger size than in the absence of the protein. Recombinant osteopontin (rOPN), which lacks phosphorylation, caused no delay in initial calcium phosphate precipitation but severely slowed crystal growth, suggesting that rOPN inhibits growth but not nucleation. rOPN treated with protein kinase CK2 to phosphorylate the molecule (p-rOPN) produced an effect similar to that of nOPN, but at higher protein concentrations and to a lesser extent. These results suggest that phosphorylations are critical to OPN’s ability to inhibit nucleation, whereas the growth of the hydroxyapatite crystals is effectively controlled by the highly acidic OPN polypeptide. This work also demonstrates that dynamic light scattering can be a powerful tool for delineating the mechanism of protein modulation of mineral formation. PMID:23457612

  17. Synthesis and cholinesterase inhibition of cativic acid derivatives.

    PubMed

    Alza, Natalia P; Richmond, Victoria; Baier, Carlos J; Freire, Eleonora; Baggio, Ricardo; Murray, Ana Paula

    2014-08-01

    Alzheimer's disease (AD) is a neurodegenerative disorder associated with memory impairment and cognitive deficit. Most of the drugs currently available for the treatment of AD are acetylcholinesterase (AChE) inhibitors. In a preliminary study, significant AChE inhibition was observed for the ethanolic extract of Grindelia ventanensis (IC??=0.79 mg/mL). This result prompted us to isolate the active constituent, a normal labdane diterpenoid identified as 17-hydroxycativic acid (1), through a bioassay guided fractionation. Taking into account that 1 showed moderate inhibition of AChE (IC??=21.1 ?M), selectivity over butyrylcholinesterase (BChE) (IC??=171.1 ?M) and that it was easily obtained from the plant extract in a very good yield (0.15% w/w), we decided to prepare semisynthetic derivatives of this natural diterpenoid through simple structural modifications. A set of twenty new cativic acid derivatives (3-6) was prepared from 1 through transformations on the carboxylic group at C-15, introducing a C2-C6 linker and a tertiary amine group. They were tested for their inhibitory activity against AChE and BChE and some structure-activity relationships were outlined. The most active derivative was compound 3c, with an IC?? value of 3.2 ?M for AChE. Enzyme kinetic studies and docking modeling revealed that this inhibitor targeted both the catalytic active site and the peripheral anionic site of this enzyme. Furthermore, 3c showed significant inhibition of AChE activity in SH-SY5Y human neuroblastoma cells, and was non-cytotoxic. PMID:25017625

  18. Boric acid inhibits embryonic histone deacetylases: A suggested mechanism to explain boric acid-related teratogenicity

    SciTech Connect

    Di Renzo, Francesca [Department of Biology, University of Milan, Via Celoria, 26. 20133 Milan (Italy); Cappelletti, Graziella [Department of Biology, University of Milan, Via Celoria, 26. 20133 Milan (Italy); Broccia, Maria L. [Department of Biology, University of Milan, Via Celoria, 26. 20133 Milan (Italy); Giavini, Erminio [Department of Biology, University of Milan, Via Celoria, 26. 20133 Milan (Italy); Menegola, Elena [Department of Biology, University of Milan, Via Celoria, 26. 20133 Milan (Italy)]. E-mail: elena.menegola@unimi.it

    2007-04-15

    Histone deacetylases (HDAC) control gene expression by changing histonic as well as non histonic protein conformation. HDAC inhibitors (HDACi) are considered to be among the most promising drugs for epigenetic treatment for cancer. Recently a strict relationship between histone hyperacetylation in specific tissues of mouse embryos exposed to two HDACi (valproic acid and trichostatin A) and specific axial skeleton malformations has been demonstrated. The aim of this study is to verify if boric acid (BA), that induces in rodents malformations similar to those valproic acid and trichostatin A-related, acts through similar mechanisms: HDAC inhibition and histone hyperacetylation. Pregnant mice were treated intraperitoneally with a teratogenic dose of BA (1000 mg/kg, day 8 of gestation). Western blot analysis and immunostaining were performed with anti hyperacetylated histone 4 (H4) antibody on embryos explanted 1, 3 or 4 h after treatment and revealed H4 hyperacetylation at the level of somites. HDAC enzyme assay was performed on embryonic nuclear extracts. A significant HDAC inhibition activity (compatible with a mixed type partial inhibition mechanism) was evident with BA. Kinetic analyses indicate that BA modifies substrate affinity by a factor {alpha} = 0.51 and maximum velocity by a factor {beta} = 0.70. This work provides the first evidence for HDAC inhibition by BA and suggests such a molecular mechanism for the induction of BA-related malformations.

  19. Hypernegative Supercoiling Inhibits Growth by Causing RNA Degradation?

    PubMed Central

    Baaklini, Imad; Usongo, Valentine; Nolent, Flora; Sanscartier, Patrick; Hraiky, Chadi; Drlica, Karl; Drolet, Marc

    2008-01-01

    Transcription-induced hypernegative supercoiling is a hallmark of Escherichia coli topoisomerase I (topA) mutants. However, its physiological significance has remained unclear. Temperature downshift of a mutant yielded transient growth arrest and a parallel increase in hypernegative supercoiling that was more severe with lower temperature. Both properties were alleviated by overexpression of RNase HI. While ribosomes in extracts showed normal activity when obtained during growth arrest, mRNA on ribosomes was reduced for fis and shorter for crp, polysomes were much less abundant relative to monosomes, and protein synthesis rate dropped, as did the ratio of large to small proteins. Altered processing and degradation of lacA and fis mRNA was also observed. These data are consistent with truncation of mRNA during growth arrest. These effects were not affected by a mutation in the gene encoding RNase E, indicating that this endonuclease is not involved in the abnormal mRNA processing. They were also unaffected by spectinomycin, an inhibitor of protein synthesis, which argued against induction of RNase activity. In vitro transcription revealed that R-loop formation is more extensive on hypernegatively supercoiled templates. These results allow us, for the first time, to present a model by which hypernegative supercoiling inhibits growth. In this model, the introduction of hypernegative supercoiling by gyrase facilitates degradation of nascent RNA; overproduction of RNase HI limits the accumulation of hypernegative supercoiling, thereby preventing extensive RNA degradation. PMID:18790862

  20. OCCURRENCE OF INHIBITORY COMPOUNDS IN SPENT GROWTH MEDIA THAT INTERFERE WITH ACID-TOLERANCE OF ENTERIC PATHOGENS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the acid-tolerance ability of enteric human pathogens is critical in determining microbial food safety and the associated risk. We have discovered naturally occurring compounds in the spent growth media, which inhibit the acid tolerance ability of several enteric human pathogens when ...

  1. XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts.

    PubMed

    Doudican, Nicole A; Byron, Sara A; Pollock, Pamela M; Orlow, Seth J

    2013-02-01

    Mebendazole (MBZ) was identified as a promising therapeutic on the basis of its ability to induce apoptosis in melanoma cell lines through a B-cell lymphoma 2 (BCL2)-dependent mechanism. We now show that in a human xenograft melanoma model, oral MBZ is as effective as the current standard of care temozolomide in reducing tumor growth. Inhibition of melanoma growth in vivo is accompanied by phosphorylation of BCL2 and decreased levels of X-linked inhibitor of apoptosis (XIAP). Reduced expression of XIAP on treatment with MBZ is partially mediated by its proteasomal degradation. Furthermore, exposure of melanoma cells to MBZ promotes the interaction of SMAC/DIABLO with XIAP, thereby alleviating XIAP's inhibition on apoptosis. XIAP expression on exposure to MBZ is indicative of sensitivity to MBZ as MBZ-resistant cells do not show reduced levels of XIAP after treatment. Resistance to MBZ can be reversed partially by siRNA knockdown of cellular levels of XIAP. Our data indicate that MBZ is a promising antimelanoma agent on the basis of its effects on key antiapoptotic proteins. PMID:23059386

  2. Growth inhibition of the eight species of microalgae by growth inhibitor from the culture of Isochrysis galbana and its isolation and identification

    Microsoft Academic Search

    Sun Yingying; Wang Changhai; Chen Jing

    2008-01-01

    A type of growth inhibitor was successfully isolated and purified from cell-free filtrates of cultural medium at the death\\u000a phase of Isochrysis galbana, and its chemical structure was confirmed by the methods of FABMS, UV, 1H-NMR, 13C-NMR and 2D NMR, which was 1-[hydroxyl-diethyl malonate]-isopropyl dodecenoic acid, C22H38O7. The results showed that the growth-inhibitor strongly inhibited the growth of Isochrysis galbana,

  3. Peptides of 2-aminopimelic acid: antibacterial agents that inhibit diaminopimelic acid biosynthesis.

    PubMed

    Berges, D A; DeWolf, W E; Dunn, G L; Grappel, S F; Newman, D J; Taggart, J J; Gilvarg, C

    1986-01-01

    Succinyl-CoA:tetrahydrodipicolinate-N-succinyltransferase is a key enzyme in the biosynthesis of diaminopimelic acid (DAP), a component of the cell wall peptidoglycan of nearly all bacteria. This enzyme converts the cyclic precursor tetrahydrodipicolinic acid (THDPA) to a succinylated acyclic product. L-2-Aminopimelic acid (L-1), an acyclic analogue of THDPA, was found to be a good substrate for this enzyme and was shown to cause a buildup of THDPA in a cell-free enzyme system but was devoid of antibacterial activity. Incorporation of 1 into a di- or tripeptide yielded derivatives that exhibited antibacterial activity against a range of Gram-negative organisms. Of the five peptide derivatives tested, (L-2-aminopimelyl)-L-alanine (6) was the most potent. These peptides were shown to inhibit DAP production in intact resting cells. High levels (30 mM) of 2-aminopimelic acid were achieved in the cytoplasm of bacteria as a result of efficient uptake of the peptide derivatives through specific peptide transport systems followed, presumably, by cleavage by intracellular peptidases. Finally, the antibacterial activity of these peptides could be reversed by DAP or a DAP-containing peptide. These results demonstrate that the peptides containing L-2-aminopimelic acid exert their antibacterial action by inhibition of diaminopimelic acid biosynthesis. PMID:3079832

  4. Potassium Inhibits Dietary Salt-Induced Transforming Growth Factor-? Production

    PubMed Central

    Ying, Wei-Zhong; Aaron, Kristal; Wang, Pei-Xuan; Sanders, Paul W.

    2009-01-01

    Human and animal studies demonstrate an untoward effect of excess dietary NaCl (salt) intake on cardiovascular function and life span. The endothelium in particular augments the production of transforming growth factor (TGF)-?, a fibrogenic growth factor, in response to excess dietary salt intake. This study explored the initiating mechanism that regulates salt-induced endothelial cell production of TGF-?. Male Sprague-Dawley rats were given diets containing different amounts of NaCl and potassium for 4 days. A bioassay for TGF-? demonstrated increased (35.2%) amounts of active TGF-? in the medium of aortic ring segments from rats on the high-salt diet compared with rats maintained on a 0.3% NaCl diet. Inhibition of the large-conductance, calcium-activated potassium channel inhibited dietary salt-induced vascular production of TGF-? but did not affect production of TGF-? by ring segments from rats on the low-salt diet. Immunohistochemical and Western analyses demonstrated the ? subunit of the calcium-activated potassium channel in endothelial cells. Increasing medium [K+] inhibited production of dietary salt-induced vascular production levels of total and active TGF-? but did not alter TGF-? production by aortic rings from rats on the 0.3% NaCl diet. Increasing dietary potassium content decreased urinary active TGF-? in animals receiving the high-salt diet but did not change urinary active TGF-? in animals receiving the low-salt diet. The findings demonstrated an interesting interaction between the dietary intake of potassium and excess NaCl and further showed the fundamental role of the endothelial calcium-activated potassium channel in the vascular response to excess salt intake. PMID:19738156

  5. Acyclic sesquiterpenes released by Candida albicans inhibit growth of dermatophytes.

    PubMed

    Brasch, Jochen; Horter, Felix; Fritsch, Daniel; Beck-Jendroschek, Vera; Tröger, Armin; Francke, Wittko

    2014-01-01

    It is unresolved as to whether fungi that share a common skin habitat might in principal interact. In in vitro screening tests with Candida albicans, Trichophytum rubrum and other common dermatophytes, we found C. albicans releases volatile compounds that inhibit growth of the dermatophytes. By applying (enantioselective) gas chromatography combined with mass spectrometry we identified 8 compounds among which stereochemically pure (3R,6E)-2,3-dihydrofarnesol (R-DHF) and (2E,6E)-farnesol (F-ol) were the main components. Synthetic R-DHF and its enantiomer, (3S,6E)-2,3-dihydrofarnesol (S-DHF), as well as F-ol were tested for their capacity to inhibit growth of dermatophytes in microtiter-plate assays over 62 h. All three compounds showed significant and concentration-dependent, to a certain extent even species-specific, inhibitory effects on T. rubrum, T. mentagrophytes, Microsporum canis and Epidermophyton floccosum. In general, S-DHF and F-ol had a pronounced effect on the dermatophytes, similar to or even stronger than that of fluconazole. E. floccosum was completely suppressed by 12.5??g/ml dihydrofarnesol, as was the inhibition caused by 50??g/ml fluconazole. Similarly, S-DHF- was more active against T. rubrum than fluconazole. To the best of our knowledge, 2,3-dihydrofarnesol has not yet been described as a volatile generated by microorganisms, and its inhibitory effect on dermatophytes is new to science. However, the relevance of this compound in interfungal interference in situ is unknown. In contrast, farnesol is a well-known semiochemical of C. albicans with intraspecific effects and a clear impact on other microorganisms. Mutual intermicrobial communication based on fungal volatiles therefore appears to be an exciting field for future investigations. PMID:23902158

  6. Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression.

    PubMed

    Yang, H; Pellegrini, L; Napolitano, A; Giorgi, C; Jube, S; Preti, A; Jennings, C J; De Marchis, F; Flores, E G; Larson, D; Pagano, I; Tanji, M; Powers, A; Kanodia, S; Gaudino, G; Pastorino, S; Pass, H I; Pinton, P; Bianchi, M E; Carbone, M

    2015-01-01

    High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information. PMID:26068794

  7. Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

    PubMed Central

    Pangburn, Heather A; Kraus, Hanna; Ahnen, Dennis J; Rice, Pamela L

    2005-01-01

    Background Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased mortality from colorectal cancer (CRC). NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2) signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF) receptor (EGFR). Methods HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068), total EGFR, phosphorylated ERK1/2 (pERK1/2), total ERK1/2, activated caspase-3, and ?-tubulin. Results EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion These results suggest that downregulation of EGFR signaling by sulindac metabolites may occur, at least in part, by inhibiting activation and expression of EGFR. Inhibition of EGFR signaling may account for part of the growth inhibitory and chemopreventive effects of these compounds. PMID:16138927

  8. Tetravanadate, Decavanadate, Keggin and Dawson Oxotungstates Inhibit Growth of S. cerevisiae

    Microsoft Academic Search

    Debbie C. Crans; Harvinder S. Bedi; Sai Li; Boyan Zhang; Kenji Nomiya; Noriko C. Kasuga; Yukihiro Nemoto; Keiichi Nomura; Kei Hashino; Yoshitaka Sakai; Yosief Tekeste; Gary Sebel; Lori-Ann E. Minasi; Jason J. Smee; Gail R. Willsky

    The Willsky group had previously shown that vanadate inhibits growth. By using the combination of yeast growth and 51V NMR spectroscopy we show that the inhibiting species is V4. Similar effects were observed when a structurally similar, chemically stable molybdate tetramer was tested. To extend this result further, detailed studies were conducted exploring the effect of V10 on cell growth

  9. Cortisol inhibits acid-induced bone resorption in vitro.

    PubMed

    Krieger, Nancy S; Frick, Kevin K; Bushinsky, David A

    2002-10-01

    Metabolic acidosis increases urine calcium excretion without an increase in intestinal calcium absorption, resulting in a net loss of bone mineral. In vitro, metabolic acidosis has been shown to initially induce physicochemical mineral dissolution and then enhance cell-mediated bone resorption. Acidic medium stimulates osteoblastic prostaglandin E(2) production, which mediates the subsequent stimulation of osteoclastic bone resorption. Glucocorticoids are also known to decrease bone mineral density, and metabolic acidosis has been shown to increase glucocorticoid production. This study tested the hypothesis that glucocorticoids would exacerbate acid-induced net calcium efflux from bone. Neonatal mouse calvariae were cultured in acid (Acid; pH = 7.06 +/- 0.01; [HCO(3)(-)] = 10.6 +/- 0.3 mM) or neutral (Ntl; pH = 7.43 +/- 0.01; [HCO(3)(-)] = 26.2 +/- 0.5 mM) medium, with or without 1 microM cortisol (Cort), and net calcium efflux and medium prostaglandin E(2) (PGE(2)) levels and osteoclastic beta-glucuronidase activity were determined. Compared with Ntl, Cort alone decreased calcium efflux, medium PGE(2), and osteoclast activity; Acid led to an increase in all three parameters. The addition of Cort to Acid led to a reduction of calcium efflux, medium PGE(2) levels and beta-glucuronidase activity compared with Acid alone. There was a significant direct correlation between medium PGE(2) concentration and net calcium efflux (r = 0.944; n = 23; P < 0.0001), between osteoclastic beta-glucuronidase activity and net calcium efflux (r = 0.663; n = 40; P < 0.001), and between medium PGE(2) concentration and beta-glucuronidase activity (r = 0.976; n = 4; P < 0.01). Thus, in vitro cortisol inhibits acid-induced, cell-mediated osteoclastic bone resorption through a decrease in osteoblastic PGE(2) production. These results suggest that the osteopenia observed in response to metabolic acidosis in vivo is not due to an increase in endogenous cortisol production. PMID:12239242

  10. Volatiles of bacterial antagonists inhibit mycelial growth of the plant pathogen Rhizoctonia solani

    Microsoft Academic Search

    Marco Kai; Uta Effmert; Gabriele Berg; Birgit Piechulla

    2007-01-01

    Bacterial antagonists are bacteria that negatively affect the growth of other organisms. Many antagonists inhibit the growth\\u000a of fungi by various mechanisms, e.g., secretion of lytic enzymes, siderophores and antibiotics. Such inhibition of fungal\\u000a growth may indirectly support plant growth. Here, we demonstrate that small organic volatile compounds (VOCs) emitted from\\u000a bacterial antagonists negatively influence the mycelial growth of the

  11. Cytostatic inhibition of cancer cell growth by lignan secoisolariciresinol diglucoside.

    PubMed

    Ayella, Allan; Lim, Soyoung; Jiang, Yu; Iwamoto, Takeo; Lin, Dingbo; Tomich, John; Wang, Weiqun

    2010-11-01

    Our previous study demonstrated that lignan metabolites enterolactone and enterodiol inhibited colonic cancer cell growth by inducing cell cycle arrest and apoptosis. However, the dietary lignans are naturally present as glycoside precursors, such as secoisolariciresinol diglucoside (SDG), which have not been evaluated yet. This study tested the hypothesis that dietary SDG might have a different effect than its metabolites in human colonic SW480 cancer cells. Treatment with SDG at 0 to 40 ?mol/L for up to 48 hours resulted in a dose- and time-dependent decrease in cell numbers, which was comparable to enterolactone. The inhibition of cell growth by SDG did not appear to be mediated by cytotoxicity, but by a cytostatic mechanism associated with an increase of cyclin A expression. Furthermore, high-performance liquid chromatography analysis indicated that SDG in the media was much more stable than enterolactone (95% of SDG survival vs 57% of enterolactone after 48-hour treatment). When the cells were treated with either enterolactone or SDG at 40 ?mol/L for 48 hours, the intracellular levels of enterolactone, as measured by high-performance liquid chromatography-mass spectrometry/electron spray ionization, were about 8.3 × 10(-8) nmol per cell; but intracellular SDG or potential metabolites were undetectable. Taken together, SDG demonstrated similar effects on cell growth, cytotoxicity, and cell cycle arrest when compared with its metabolite enterolactone. However, the reliable stability and undetectable intracellular SDG in treated cells may suggest that metabolism of SDG, if exposed directly to the colonic cells, could be different from the known degradation by microorganisms in human gut. PMID:21130295

  12. Disruption of Retinoic Acid Receptor Alpha Reveals the Growth Promoter Face of Retinoic Acid

    PubMed Central

    Ren, MingQiang; Ghidoni, Riccardo; Sacchi, Nicoletta

    2007-01-01

    Background Retinoic acid (RA), the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs), exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RAR?, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591). The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RAR?, through differential regulation of the “rheostat” comprising ceramide (CER), the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P), the sphingolipid with prosurvival activity. Methodology/Principal Findings We found that functional inhibition of endogenous RAR? in breast cancer cells by using either RAR? specific antagonists or a dominant negative RAR? mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase)-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling. Conclusions/Significance In the presence of functional RAR?, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RAR?, RA–in a non-RAR-mediated fashion–promotes cell growth by activating the prosurvival S1P signaling. These two distinct, yet integrated processes apparently concur to the growth-promoter effects of RA. PMID:17786207

  13. A laboratory and field investigation of naphthenic acid corrosion inhibition

    SciTech Connect

    Zetlmeisl, M.J. [Petrolite Corp., St. Louis, MO (United States)

    1995-11-01

    This paper presents results of a laboratory and field study of naphthenic acid corrosion and the development of an effective chemical inhibitor for this type of corrosive attack. In the laboratory corrosion test, which involved 20 hour weight loss measurements in high flash solvent with a total acid number (TAN) of 16 mg KOH/gm at a temperature of 600 F (316 C), blank corrosion rates averaged 140 to 150 mpy (3.56 to 3.81 mm/y). Inhibited rates averaged about 10 to 12 mpy (0.254 to 0.305 mm/y). The field test was carried out on a heavy vacuum gas oil (HVGO) stream at 550 F (288 C) . Blanks varied from a high of 425 mpy (10.79 mm/y) for a 24 hour test to a low of about 100 mpy (2.54 mm/y) for a 150 hour test. Both electrical resistance (ER) probes and weight loss coupons showed corrosion rates below 5 mpy (0.127 mm/y) as long as they were adequately passivated. Passivation consisted of exposing the coupons to a high inhibitor dosage for a relatively short time to establish a protective layer on the metal surface. Acceleration of corrosion rates by the interaction between some reportedly corrosive refinery fluids and HCl vapor is also demonstrated. A model, which represents naphthenic acid and other potentially corrosive materials as nonaqueous electrolytes, is presented.

  14. 4-Methylumbelliferone inhibits hepatocellular carcinoma growth by decreasing IL-6 production and angiogenesis.

    PubMed

    Piccioni, Flavia; Fiore, Esteban; Bayo, Juan; Atorrasagasti, Catalina; Peixoto, Estanislao; Rizzo, Manglio; Malvicini, Mariana; Tirado-González, Irene; García, Mariana G; Alaniz, Laura; Mazzolini, Guillermo

    2015-08-01

    Cirrhosis is characterized by an excessive accumulation of extracellular matrix components including hyaluronic acid (HA) and is widely considered a preneoplastic condition for hepatocellular carcinoma (HCC). 4-Methylumbelliferone (4MU) is an inhibitor of HA synthesis and has anticancer activity in an orthotopic HCC model with underlying fibrosis. Our aim was to explore the effects of HA inhibition by 4MU orally administered on tumor microenvironment. Hepa129 tumor cells were inoculated orthotopically in C3H/HeJ male mice with fibrosis induced by thioacetamide. Mice were orally treated with 4MU. The effects of 4MU on angiogenesis were evaluated by immunostaining of CD31 and quantification of proangiogenic factors (vascular endothelial growth factor, VEGF, interleukin-6, IL-6 and C-X-C motif chemokine 12, CXCL12). IL-6 was also quantified in Hepa129 cells in vitro after treatment with 4MU. Migration of endothelial cells and tube formation were also analyzed. As a result, 4MU treatment decreases tumor growth and increased animal survival. Systemic levels of VEGF were significantly inhibited in 4MU-treated mice. Expression of CD31 was reduced after 4MU therapy in liver parenchyma in comparison with control group. In addition, mRNA expression and protein levels of IL-6 and VEGF were inhibited both in tumor tissue and in nontumoral liver parenchyma. Interestingly, IL-6 production was dramatically reduced in Kupffer cells isolated from 4MU-treated mice, and in Hepa129 cells in vitro. Besides, 4MU was able to inhibit endothelial cell migration and tube formation. In conclusion, 4MU has antitumor activity in vivo and its mechanisms of action involve an inhibition of angiogenesis and IL-6 production. 4MU is an orally available molecule with potential for HCC treatment. PMID:25882295

  15. Effect of growth conditions on flow-induced inhibition of population growth of a red-tide dinoflagellate

    Microsoft Academic Search

    Andrew R. Juhl; Vivianna Velazquez; Michael I. Latz

    2000-01-01

    The population growth of some dinoflagellates is known to be reduced by exposure to fluid flow. The red-tide dinoflagellate Lingulodinium polyedrum was used to examine the effect of growth conditions on flow-induced inhibition of population growth. Three factors were tested: time of exposure relative to the light : dark (LD) cycle, illumination level, and culture growth phase (early vs. late

  16. ASB-2 inhibits growth and promotes commitment in myeloid leukemia cells.

    PubMed

    Guibal, Florence C; Moog-Lutz, Christel; Smolewski, Piotr; Di Gioia, Yolande; Darzynkiewicz, Zbigniew; Lutz, Pierre G; Cayre, Yvon E

    2002-01-01

    In acute promyelocytic leukemia (APL) cells harboring the promyelocytic leukemia retinoic acid receptor alpha (PML-RARalpha) chimeric protein, retinoic acid (RA)-induced differentiation is triggered through a PML-RARalpha signaling resulting in activation of critical target genes. Induced differentiation of APL cells is always preceded by withdrawal from the cell cycle and commitment events leading to terminal differentiation. Here we have identified the human ankyrin repeat-containing protein with a suppressor of cytokine signaling box-2 (ASB-2) cDNA, as a novel RA-induced gene in APL cells. PML-RARalpha strongly enhanced RA-induced ASB-2 mRNA expression. In myeloid leukemia cells, ASB-2 expression induced growth inhibition and chromatin condensation recapitulating early events critical to RA-induced differentiation of APL cells. PMID:11682484

  17. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo

    Microsoft Academic Search

    K. Jin Kim; Bing Li; Jane Winer; Mark Armanini; Nancy Gillett; Heidi S. Phillips; Napoleone Ferrara

    1993-01-01

    THE development of new blood vessels (angiogenesis) is required for many physiological processes including embryogenesis, wound healing and corpus luteum formation1,2. Blood vessel neoformation is also important in the pathogenesis of many disorders1-5, particularly rapid growth and metastasis of solid tumours3-5. There are several potential mediators of tumour angiogenesis, including basic and acidic fibroblast growth factors, tumour necrosis factor-alpha and

  18. Inhibition of norsolorinic acid accumulation to Aspergillus parasiticus by marine actinomycetes

    NASA Astrophysics Data System (ADS)

    Yan, Peisheng; Shi, Cuijuan; Shen, Jihong; Wang, Kai; Gao, Xiujun; Li, Ping

    2014-11-01

    Thirty-six strains of marine actinomycetes were isolated from a sample of marine sediment collected from the Yellow Sea and evaluated in terms of their inhibitory activity on the growth of Aspergillus parasiticus and the production of norsolorinic acid using dual culture plate assay and agar diffusion methods. Among them, three strains showed strong antifungal activity and were subsequently identified as Streptomyces sp. by 16S rRNA gene sequencing analysis. The supernatant from the fermentation of the MA01 strain was extracted sequentially with chloroform and ethyl acetate, and the activities of the extracts were determined by tip culture assay. The assay results show that both extracts inhibited mycelium growth and toxin production, and the inhibitory activities of the extracts increased as their concentrations increased. The results of this study suggest that marine actinomycetes are biologically important for the control of mycotoxins, and that these bacteria could be used as novel biopesticides against mycotoxins.

  19. Ursolic acid and oleanolic acid from Eriobotrya fragrans inhibited the viability of A549 cells.

    PubMed

    Yuan, Yuan; Gao, Yongshun; Song, Gang; Lin, Shunquan

    2015-02-01

    Loquat {Eriobotrya japonica (Lindl.)}, a kind of Chinese herb, has many efficacies such as anti-inflammatory, antimicrobial and curing chronic bronchitis. However, reports on the pharmacological action of wild loquat extract are limited. In this work, the A549 cell line was selected to study the inhibitory effect of ursolic acid and oleanolic acid (UA, OA) from the leaves of E. fragrans. Results showed that UA/OA inhibited A549 cell viability and induced apoptosis in a dose and time dependent manner. The cell fraction in the G0/G1 phase dramatically increased under treatment with UA/OA. Data showed that UA activated the expression of PARP. UA and OA down-regulated MMP-2 and Bcl-2; on the contrary, they up-regulated Bid. This work demonstrated that UA/OA extracted from wild loquat leaves can significantly inhibit the viability of A549 cells. PMID:25920250

  20. Inhibition of ochratoxin A production and growth of Aspergillus species by phenolic antioxidant compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The phenolic antioxidants, gallic acid, vanillic acid, protocatechuic acid, 4-hydroxybenzoic acid, catechin, caffeic acid, and chlorogenic acid were studied for their effects on ochratoxin A (OTA) production and fungal growth of ochratoxigenic Aspergilli. Of the 12 strains tested, which included A....

  1. Copper inhibition of the thiobarbituric acid reaction in Bedlington terriers.

    PubMed

    Hultgren, B D; Menken, B Z; Csallany, A S

    1986-04-01

    The effect of copper on thiobarbituric acid (TBA) reaction values, an index of lipid peroxidation, was examined in Bedlington Terriers, healthy dogs, and rats. High hepatic concentrations of copper appeared to lower TBA values in the inherited, chronic, progressive hepatic degeneration of Bedlington Terriers, a disease associated with copper toxicosis. The suspected TBA inhibition was confirmed when Cu2+ was added to homogenates of healthy dog or rat liver or a malondialdehyde standard. The amount of copper added approximated that in diseased Bedlington Terriers. Because of the interference by copper, the TBA test was judged to be an inappropriate test for the evaluation of lipid peroxidation in samples containing high copper concentrations such as those in diseased Bedlington Terriers. PMID:3963583

  2. Inhibition of Growth and Gene Expression by PNA-peptide Conjugates in Streptococcus pyogenes

    PubMed Central

    Patenge, Nadja; Pappesch, Roberto; Krawack, Franziska; Walda, Claudia; Mraheil, Mobarak Abu; Jacob, Anette; Hain, Torsten; Kreikemeyer, Bernd

    2013-01-01

    While Streptococcus pyogenes is consistently susceptible toward penicillin, therapeutic failure of penicillin treatment has been reported repeatedly and a considerable number of patients exhibit allergic reactions to this substance. At the same time, streptococcal resistance to alternative antibiotics, e.g., macrolides, has increased. Taken together, these facts demand the development of novel therapeutic strategies. In this study, S. pyogenes growth was inhibited by application of peptide-conjugated antisense-peptide nucleic acids (PNAs) specific for the essential gyrase A gene (gyrA). Thereby, HIV-1 Tat peptide-coupled PNAs were more efficient inhibitors of streptococcal growth as compared with (KFF)3K-coupled PNAs. Peptide-anti-gyrA PNAs decreased the abundance of gyrA transcripts in S. pyogenes. Growth inhibition by antisense interference was enhanced by combination of peptide-coupled PNAs with protein-level inhibitors. Antimicrobial synergy could be detected with levofloxacin and novobiocin, targeting the gyrase enzyme, and with spectinomycin, impeding ribosomal function. The prospective application of carrier peptide-coupled antisense PNAs in S. pyogenes covers the use as an antimicrobial agent and the employment as a knock-down strategy for the investigation of virulence factor function. PMID:24193033

  3. Effect of Trichoderma on plant growth: A balance between inhibition and growth promotion

    Microsoft Academic Search

    M. A. Ousley; J. M. Lynch; J. M. Whipps

    1993-01-01

    The effect of lettuce (Latuca sativa L.) germination and growth in nonsterilized potting compost of 0.1% and 1.0% w\\/w incorporation of fermenter biomass inocula of six strains of Trichoderma was investigated. Except for strains WT and T35 at 0.1 % w\\/w, all inocula inhibited germination. Biomass of strains WT, T35, 20, and 47 at 1.0% promoted shoot fresh weight, whereas

  4. ?-Pinene inhibited germination and early growth involves membrane peroxidation.

    PubMed

    Chowhan, Nadia; Singh, Harminder Pal; Batish, Daizy R; Kaur, Shalinder; Ahuja, Nitina; Kohli, Ravinder K

    2013-06-01

    ?-Pinene, an oxygenated monoterpene, is abundantly found in the environment and widely occurring in plants as a constituent of essential oils. We investigated the phytotoxicity of ?-pinene against two grassy (Phalaris minor, Echinochloa crus-galli) and one broad-leaved (Cassia occidentalis) weeds in terms of germination and root and shoot growth. ?-Pinene (0.02-0.80 mg/ml) inhibited the germination, root length, and shoot length of test weeds in a dose-response manner. The inhibitory effect of ?-pinene was greater in grassy weeds and on root growth than on shoot growth. ?-Pinene (0.04-0.80 mg/ml) reduced the root length in P. minor, E. crus-galli, and C. occidentalis over that in the control by 58-60, 44-92, and 26-85 %, respectively. In contrast, shoot length was reduced over the control by 45-97 % in P. minor, 48-78 % in E. crus-galli, and 11-75 % in C. occidentalis at similar concentrations. Further, we examined the impact of ?-pinene on membrane integrity in P. minor as one of the possible mechanisms of action. Membrane integrity was evaluated in terms of lipid peroxidation, conjugated diene content, electrolyte leakage, and the activity of lipoxygenases (LOX). ?-Pinene (?0.04 mg/ml) enhanced electrolyte leakage by 23-80 %, malondialdehyde content by 15-67 %, hydrogen peroxide content by 9-39 %, and lipoxygenases activity by 38-383 % over that in the control. It indicated membrane peroxidation and loss of membrane integrity that could be the primary target of ?-pinene. Even the enhanced (9-62 %) activity of protecting enzymes, peroxidases (POX), was not able to protect the membranes from ?-pinene (0.04-0.20 mg/ml)-induced toxicity. In conclusion, our results show that ?-pinene inhibits root growth of the tested weed species through disruption of membrane integrity as indicated by enhanced peroxidation, electrolyte leakage, and LOX activity despite the upregulation of POX activity. PMID:22936022

  5. Growth Inhibition of Listeria monocytogenes, Salmonella enterica, and Escherichia coli O157:H7 by D-tryptophan as an incompatible solute.

    PubMed

    Koseki, Shigenobu; Nakamura, Nobutaka; Shiina, Takeo

    2015-04-01

    Under osmotic stress, bacterial cells uptake compatible solutes such as glycine-betaine to maintain homeostasis. It is unknown whether incompatible solutes exist that are similar in structure to compatible solutes but have adverse physiological effects on bacterial physiology. The objective of this study was to evaluate solute incompatibility of various amino acids against bacterial growth. Bacterial growth was evaluated by changes in optical density at 595 nm in peptone-yeast-glucose (PYG) broth. Twenty-three amino acids with L and/or D isomers were examined for the effect of bacterial growth inhibition. Among the various amino acids examined, D-tryptophan (? 40 mM) in PYG broth supplemented with 0 to 4% (wt/vol) salt inhibited the growth of Listeria monocytogenes, Salmonella enterica, and Escherichia coli O157:H7 at 25 °C. D-Tryptophan (30 to 40 mM) completely inhibited the growth of E. coli O157:H7 and Salmonella in the presence of >3% salt, but the growth of L. monocytogenes was not completely inhibited under the same conditions. Low concentrations of salt (0 to 2% NaCl) with D-tryptophan did not significantly inhibit the growth of all bacteria except L. monocytogenes, which was relatively inhibited at 0% NaCl. The effect of D-tryptophan differed depending on the bacterial species, illustrating the difference between gram-positive and gram-negative bacteria. These results indicate that the uptake of D-tryptophan as a compatible solute during osmotic stress may inhibit bacterial growth. The antibacterial effect of D-tryptophan found in this study suggests that D-tryptophan could be used as a novel preservative for controlling bacterial growth in foods. PMID:25836411

  6. Promotion of plant growth by polymers of lactic acid

    Microsoft Academic Search

    Alan M. Kinnersley; Taylor C. Scott; John H. Yopp; George H. Whitten

    1990-01-01

    Polymers of L-lactic acid are shown to promote plant growth. Dry weight of duckweed (Lemna minor L.) and corn (Zea mays L) was more than doubled when plants were grown in media containing the dimer of L-lactic acid, L-lactoyllactic acid. Higher polymers were equally effective at increasing plant biomass. Monomeric lactic acid and polymers of D-lactic acid showed no biological

  7. GRIM-1, a Novel Growth Suppressor, Inhibits rRNA Maturation by Suppressing Small Nucleolar RNAs

    PubMed Central

    Srivastava, Varsha; Gade, Padmaja; Hofmann, Edward R.; Ahmed, Hafiz; Reddy, Sekhar P.; Kalvakolanu, Dhananjaya V.

    2011-01-01

    We have recently isolated novel IFN-inducible gene, Gene associated with Retinoid-Interferon-induced Mortality-1 (GRIM-1), using a genetic technique. Moderate ectopic expression of GRIM-1 caused growth inhibition and sensitized cells to retinoic acid (RA)/IFN-induced cell death while high expression caused apoptosis. GRIM-1 depletion, using RNAi, conferred a growth advantage. Three protein isoforms (1?, 1? and 1?) with identical C-termini are produced from GRIM-1 mRNA. We show that GRIM-1 isoforms interact with NAF1 and DKC1, two essential proteins required for box H/ACA sno/sca RNP biogenesis and suppresses box H/ACA RNA levels in mammalian cells by delocalizing NAF1. Suppression of these small RNAs manifests as inefficient rRNA maturation and growth suppression. Interestingly, yeast Shq1p also caused growth suppression in mammalian cells. Consistent with its growth-suppressive property, GRIM-1 expression is lost in a number of human primary prostate tumors. Our observations support a recent study that GRIM-1 might act as a co-tumor suppressor in the prostate. PMID:21931644

  8. MECHANISMS OF FLUID SHEAR-INDUCED INHIBITION OF POPULATION GROWTH IN A RED-TIDE DINOFLAGELLATE

    EPA Science Inventory

    Net population growth of some dinoflagellates is inhibited by fluid shear at shear stresses comparable with those generated during oceanic turbulence. Decreased net growth may occur through lowered cell division, increased mortality, or both. The dominant mechanism under various ...

  9. Nucleic Acid Conformational Changes Essential for HIV-1 Nucleocapsid Protein-mediated Inhibition of

    E-print Network

    Levin, Judith G.

    Nucleic Acid Conformational Changes Essential for HIV-1 Nucleocapsid Protein-mediated Inhibition) is a nucleic acid chaperone protein that has been shown to greatly facilitate the nucleic acid rearrangements and a TAR-containing acceptor RNA molecule, we find that when both nucleic acids are present, NC facilitates

  10. Growth of Steptomyces hygroscopicus in rotating-wall bioreactor under simulated microgravity inhibits rapamycin production

    NASA Technical Reports Server (NTRS)

    Fang, A.; Pierson, D. L.; Mishra, S. K.; Demain, A. L.

    2000-01-01

    Growth of Streptomyces hygroscopicus under conditions of simulated microgravity in a rotating-wall bioreactor resulted in a pellet form of growth, lowered dry cell weight, and inhibition of rapamycin production. With the addition of Teflon beads to the bioreactor, growth became much less pelleted, dry cell weight increased but rapamycin production was still markedly inhibited. Growth under simulated microgravity favored extracellular production of rapamycin, in contrast to a greater percentage of cell-bound rapamycin observed under normal gravity conditions.

  11. Gangliosides GD1b, GT1b, and GQ1b Suppress the Growth of Human Melanoma by Inhibiting Interleukin8 Production: the Inhibition of Adenylate Cyclase1

    Microsoft Academic Search

    Naoko Kanda; Kenji Nakai; Shinichi Watanabe

    2001-01-01

    We studied the effects of various gangliosides on in vitro growth of human metastatic melanoma WM266-4. GD1b, GT1b, and GQ1b inhibited 3H-thymidine uptake and growth rate of WM266-4 whereas the other gangliosides were ineffective. The growth inhibition by GD1b, GT1b, and GQ1b was counteracted by interleukin-8 but not by the other growth factors. The growth inhibition by gangliosides was not

  12. Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth

    PubMed Central

    Ono, Masanori; Yin, Ping; Navarro, Antonia; Moravek, Molly B.; Coon, John S.; Druschitz, Stacy A.; Gottardi, Cara J.; Bulun, Serdar E.

    2014-01-01

    Objective Dysregulation of WNT signaling plays a central role in tumor cell growth and progression. Our goal was to assess the effect of three WNT/?-catenin pathway inhibitors, Inhibitor of ?-Catenin And TCF4 (ICAT), niclosamide, and XAV939 on the proliferation of primary cultures of human uterine leiomyoma cells. Design Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy. Setting University research laboratory. Patient(s) Women (n=38) aged 27–53 years undergoing surgery. Intervention(s) Adenoviral ICAT overexpression or treatment with varying concentrations of niclosamide or XAV939. Main Outcome Measure(s) Cell proliferation, cell death, WNT/?-catenin target gene expression or reporter gene regulation, ?-catenin levels and cellular localization. Result(s) ICAT, niclosamide, or XAV939 inhibit WNT/?-catenin pathway activation and exert anti-proliferative effects in primary cultures of human leiomyoma cells. Conclusion(s) Three WNT/?-catenin pathway inhibitors specifically block human leiomyoma growth and proliferation, suggesting that the canonical WNT pathway may be a potential therapeutic target for the treatment of uterine leiomyoma. Our findings provide rationale for further preclinical and clinical evaluation of ICAT, niclosamide, and XAV939 as candidate anti-tumor agents for uterine leiomyoma. PMID:24534281

  13. Sunitinib and SU11652 inhibit acid sphingomyelinase, destabilize lysosomes, and inhibit multidrug resistance.

    PubMed

    Ellegaard, Anne-Marie; Groth-Pedersen, Line; Oorschot, Viola; Klumperman, Judith; Kirkegaard, Thomas; Nylandsted, Jesper; Jäättelä, Marja

    2013-10-01

    Defective apoptosis signaling and multidrug resistance are major barriers for successful cancer treatment. To identify drugs capable of targeting treatment-resistant cancer cells, we screened small-molecule kinase inhibitor libraries for compounds that decrease the viability of apoptosis-resistant human MCF7-Bcl-2 breast cancer cells. SU11652, a multitargeting receptor tyrosine kinase inhibitor, emerged as the most potent compound in the screen. In addition to MCF7-Bcl-2 cells, it effectively killed HeLa cervix carcinoma, U-2-OS osteosarcoma, Du145 prostate carcinoma, and WEHI-S fibrosarcoma cells at low micromolar concentration. SU11652 accumulated rapidly in lysosomes and disturbed their pH regulation and ultrastructure, eventually leading to the leakage of lysosomal proteases into the cytosol. Lysosomal destabilization was preceded by an early inhibition of acid sphingomyelinase, a lysosomal lipase that promotes lysosomal membrane stability. Accordingly, Hsp70, which supports cancer cell survival by increasing lysosomal acid sphingomyelinase activity, conferred partial protection against SU11652-induced cytotoxicity. Remarkably, SU11652 killed multidrug-resistant Du145 prostate cancer cells as effectively as the drug-sensitive parental cells, and subtoxic concentrations of SU11652 effectively inhibited multidrug-resistant phenotype in Du145 prostate cancer cells. Notably, sunitinib, a structurally almost identical and widely used antiangiogenic cancer drug, exhibited similar lysosome-dependent cytotoxic activity, albeit with significantly lower efficacy. The significantly stronger lysosome-targeting activity of SU11652 suggests that it may display better efficacy in cancer treatment than sunitinib, encouraging further evaluation of its anticancer activity in vivo. Furthermore, our data provide a rationale for novel approaches to target drug-resistant cancers by combining classic chemotherapy with sunitinib or SU11652. PMID:23920274

  14. Inhibition of Listeria monocytogenes and Salmonella by combinations of oriental mustard, malic acid, and EDTA.

    PubMed

    Olaimat, Amin N; Holley, Richard A

    2014-04-01

    The antimicrobial activities of oriental mustard extract alone or combined with malic acid and EDTA were investigated against Salmonella spp. or Listeria monocytogenes at different temperatures. Five strain Salmonella or L. monocytogenes cocktails were separately inoculated in Brain Heart Infusion broth containing 0.5% (w/v) aqueous oriental mustard extract and incubated at 4 °C to 21 °C for 21 d. For inhibitor combination tests, Salmonella Typhimurium 02:8423 and L. monocytogenes 2-243 were individually inoculated in Mueller Hinton broth containing the mustard extract with either or both 0.2% (w/v) malic acid and 0.2% (w/v) EDTA and incubated at 10 °C or 21 °C for 10 to 14 d. Mustard extract inhibited growth of the L. monocytogenes cocktail at 4 °C up to 21 d (2.3 log10 CFU/mL inhibition) or at 10 °C for 7 d (2.4 log10 CFU/mL inhibition). Salmonella spp. viability was slightly, but significantly reduced by mustard extract at 4 °C by 21 d. Although hydrolysis of sinigrin in mustard extract by both pathogens was 2 to 6 times higher at 21 °C than at 4 °C to 10 °C, mustard was not inhibitory at 21 °C, perhaps because of the instability of its hydrolysis product (allyl isothiocyanate). At 21 °C, additive inhibitory effects of mustard extract with EDTA or malic acid led to undetectable levels of S. Typhimurium and L. monocytogenes by 7 d and 10 d, respectively. At 10 °C, S. Typhimurium was similarly susceptible, but combinations of antimicrobials were not more inhibitory to L. monocytogenes than the individual agents. PMID:24649979

  15. Fibroblast growth factor 7 inhibits cholesterol 7{alpha}-hydroxylase gene expression in hepatocytes

    SciTech Connect

    Sun, Zhichao [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Yu, Xuemei [Department of Endocrinology, Fengxian Central Hospital, Shanghai (China)] [Department of Endocrinology, Fengxian Central Hospital, Shanghai (China); Wu, Weibin; Jia, Dongwei; Chen, Yinle; Ji, Lingling; Liu, Xijun; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Li, Yintao [Institute of Endocrinology and Diabetology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai (China)] [Institute of Endocrinology and Diabetology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai (China); Yang, Lili [Department of Endocrinology, Fengxian Central Hospital, Shanghai (China)] [Department of Endocrinology, Fengxian Central Hospital, Shanghai (China); Ruan, Yuanyuan; Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Ren, Shifang, E-mail: renshifang@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Zhang, Songwen, E-mail: songwenzhang@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer FGF7 strongly and rapidly down-regulates the expression of CYP7A1 in hepatocytes. Black-Right-Pointing-Pointer FGF7 suppresses the expression of CYP7A1 via FGFR2 and downstream JNK activation. Black-Right-Pointing-Pointer Blocking FGF7 abrogates HSC-induced inhibition of CYP7A1 expression in hepatocytes. -- Abstract: Cholesterol 7{alpha}-hydroxylase (CYP7A1) is the initial and rate-limiting enzyme for bile acid synthesis. Transcription of the CYP7A1 gene is regulated by bile acids, nuclear receptors and cytokines. Fibroblast growth factor 7 (FGF7) secreted from activated hepatic stellate cells (HSC) during chronic liver fibrosis regulates hepatocyte survival and liver regeneration. In the carbon tetrachloride (CCl{sub 4})-induced fibrotic mouse liver, we demonstrated that the expression of CYP7A1 was largely decreased while the expression of FGF7 was significantly increased. We further demonstrated that FGF7 inhibited CYP7A1 gene expression in hepatocytes. Knockdown study by short interfering RNA, kinase inhibition and phosphorylation assays revealed that the suppression of CYP7A1 expression by FGF7 was mediated by FGFR2 and its downstream JNK signaling cascade. The FGF7 neutralizing antibody restored CYP7A1 expression in Hep3B cells treated with conditioned medium from HSC. In summary, the data suggest that FGF7 is a novel regulator of CYP7A1 expression in hepatocytes and may prevent hepatocytes from accumulating toxic bile acids during liver injury and fibrosis.

  16. Furfural Inhibits Growth by Limiting Sulfur Assimilation in Ethanologenic Escherichia coli Strain LY180?

    PubMed Central

    Miller, Elliot N.; Jarboe, Laura R.; Turner, Peter C.; Pharkya, Priti; Yomano, Lorraine P.; York, Sean W.; Nunn, David; Shanmugam, K. T.; Ingram, Lonnie O.

    2009-01-01

    A wide variety of commercial products can be potentially made from monomeric sugars produced by the dilute acid hydrolysis of lignocellulosic biomass. However, this process is accompanied by side products such as furfural that hinder microbial growth and fermentation. To investigate the mechanism of furfural inhibition, mRNA microarrays of an ethanologenic strain of Escherichia coli (LY180) were compared immediately prior to and 15 min after a moderate furfural challenge. Expression of genes and regulators associated with the biosynthesis of cysteine and methionine was increased by furfural, consistent with a limitation of these critical metabolites. This was in contrast to a general stringent response and decreased expression of many other biosynthetic genes. Of the 20 amino acids individually tested as supplements (100 ?M each), cysteine and methionine were the most effective in increasing furfural tolerance with serine (precursor of cysteine), histidine, and arginine of lesser benefit. Supplementation with other reduced sulfur sources such as d-cysteine and thiosulfate also increased furfural tolerance. In contrast, supplementation with taurine, a sulfur source that requires 3 molecules of NADPH for sulfur assimilation, was of no benefit. Furfural tolerance was also increased by inserting a plasmid encoding pntAB, a cytoplasmic NADH/NADPH transhydrogenase. Based on these results, a model is proposed for the inhibition of growth in which the reduction of furfural by YqhD, an enzyme with a low Km for NADPH, depletes NADPH sufficiently to limit the assimilation of sulfur into amino acids (cysteine and methionine) by CysIJ (sulfite reductase). PMID:19684179

  17. A cortical astrocyte subpopulation inhibits axon growth in vitro and in vivo.

    PubMed

    Liu, Rui; Wang, Zhe; Gou, Lin; Xu, Hanpeng

    2015-08-01

    Astrocytes are the most heterogeneous and predominant glial cell type in the central nervous system. However, the functional significance of this heterogeneity remains to be elucidated. Following injury, damaged astrocytes inhibit axonal regeneration in vivo and in vitro. Cultured primary astrocytes are commonly considered good supportive substrates for neuron attachment and axon regeneration. However, it is not known whether different populations of cells in the heterogeneous astrocyte culture affect neuron behavior in the same way. In the present study, the effect of astrocyte heterogeneity on neuronal attachment and neurite outgrowth was examined using an in vitro and in vivo co?culture system. In vitro, neonatal cortical astrocytes were co?cultured with purified dorsal root ganglia (DRG) neurons and astrocyte growth morphology, neuron attachment and neurite growth were evaluated. The results demonstrated that the heterogeneous astrocyte cells showed two different types of growth pattern, typical and atypical. Typical astrocytes were supportive to neuron attachment and neurite growth, which was consistent with previous studies, whereas atypical astrocytes inhibited neuron attachment and neurite growth. These inhibitory astrocytes exhibited a special growth pattern with various shapes and sizes, a high cell density, few oligodendrocytes on the top layer and occupied a smaller growth area compared with typical astrocytes. Neurites extended freely on typical supportive astrocyte populations, however, moved away when they reached atypical astrocyte growth pattern. Neurons growing on the atypical astrocyte pattern demonstrated minimal neurite outgrowth and these neurites had a dystrophic appearance, however, neuronal survival was unaffected. Immunocytochemistry studies demonstrated that these atypical inhibitory astrocytes were glial fibrillary acidic protein (GFAP) positive cells. The existence of inhibitory astrocyte subpopulations in normal astrocytes reflects the complexity of the function of astrocyte populations. In vivo, DRG neurons in grey matter did not show neurite growth, while DRG neurons survived and showed robust axon outgrowth along the corpus callosum. In conclusion, further studies on this new type of inhibitory astrocyte subpopulation may deepen our understanding of the complex biology of astrocytes. PMID:25936767

  18. Eicosapentaenoic acid and sulphur substituted fatty acid analogues inhibit the proliferation of human breast cancer cells in culture

    Microsoft Academic Search

    Farzaad Abdi-Dezfuli; Livar Frøyland; Thor Thorsen; Asbjøorn Aakvaag; Rolf K. Berge

    1997-01-01

    Numerous studies have shown dietary fatty acids toinfluence the progression of several types of cancers.The purpose of the present investigation was toexamine the influence of various types of fattyacids, including ?-3 fatty acids and a newclass of hypolipidemic peroxisome proliferating fatty acid analogues,namely the 3-thia fatty acids, on MCF-7 humanbreast cancer cell growth. 3-thia fatty acids representnon-ß-oxidizable fatty acid analogues

  19. Lipoteichoic Acid Inhibits Interleukin-2 (IL-2) Function by Direct Binding to IL-2

    PubMed Central

    Plitnick, Lisa M.; Jordan, Robert A.; Banas, Jeffrey A.; Jelley-Gibbs, Dawn M.; Walsh, Mary C.; Preissler, Mark T.; Gosselin, Edmund J.

    2001-01-01

    Lipoteichoic acid (LTA) is associated with the cell envelope of most gram-positive bacteria. Although previously thought to act mainly as a virulence factor by virtue of its adhesive nature, evidence is now provided that LTA can also suppress the function of interleukin-2 (IL-2), an autocrine growth factor for T cells. LTA from four separate bacterial strains lowered the levels of detectable IL-2 during a peripheral blood mononuclear cell response to the antigen tetanus toxoid (TT). T-cell proliferation in response to TT was similarly inhibited by LTA. In contrast, levels of detectable gamma interferon increased. In addition, LTA inhibited IL-2 detection by enzyme-linked immunosorbent assay (ELISA) and blocked the proliferative response of an IL-2-dependent T-cell line to soluble IL-2. Further studies using ELISA demonstrated that LTA blocks IL-2 detection and function by binding directly to IL-2. Flow cytometric analysis revealed that IL-2 binding to T cells is inhibited in the presence of purified LTA but not LTA plus anti-LTA monoclonal antibody. In summary, these studies demonstrate a novel effect of LTA on the immune response through direct binding to IL-2 and inhibition of IL-2 function. Importantly, gram-positive organisms from which LTA is obtained not only play an important role in the pathology of diseases such as bacterial endocarditis, septic shock, acute respiratory distress syndrome, and multiple organ failure but also comprise a significant portion of commensal populations within the human host. Inhibition of IL-2 function by LTA may represent yet another mechanism by which gram-positive bacteria dampen the host immune response and facilitate survival. Thus, LTA provides a potential target for therapeutic intervention when gram-positive organisms are involved. PMID:11527813

  20. PPAR? inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth.

    PubMed

    Abu Aboud, Omran; Donohoe, Dallas; Bultman, Scott; Fitch, Mark; Riiff, Tim; Hellerstein, Marc; Weiss, Robert H

    2015-06-01

    Kidney cancer [renal cell carcinoma (RCC)] is the sixth-most-common cancer in the United States, and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 yr due to the development of therapeutic resistance. We previously identified peroxisome proliferator-activating receptor-? (PPAR?) as a potential therapeutic target for this disease and showed that a specific PPAR? antagonist, GW6471, induced apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPAR? inhibition attenuates components of RCC metabolic reprogramming, capitalizing on the Warburg effect. The specific PPAR? inhibitor GW6471, as well as a siRNA specific to PPAR?, attenuates the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPAR? antagonism also blocks the enhanced glycolysis that has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific inhibition of glycolysis corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model, with minimal obvious toxicity, a finding associated with the expected on-target effects on c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPAR? antagonism. Our data support the concept that targeting PPAR?, with or without concurrent inhibition of glycolysis, is a potential novel and effective therapeutic approach for RCC that targets metabolic reprogramming in this tumor. PMID:25810260

  1. Inhibiting Plasmodium falciparum growth and heme detoxification pathway using heme-binding DNA aptamers

    PubMed Central

    Niles, Jacquin C.; DeRisi, Joseph L.; Marletta, Michael A.

    2009-01-01

    The human parasite Plasmodium falciparum enzymatically digests hemoglobin during its intra-erythrocytic developmental stages in acidic food vacuole compartments. The released heme is rapidly detoxified by polymerization into the chemically inert pigment, hemozoin. Several heme-binding anti-malarial compounds, such as chloroquine, efficiently inhibit this process, and this is believed to be the predominant mechanism by which these drugs induce parasite toxicity. In an effort to expand the biochemical tools available for exploration of this pathogen's basic biology, we chose this heme-detoxification pathway as a model system for exploring the suitability of DNA aptamers for modulating this essential parasite biochemical pathway. In this report, we demonstrate that heme-binding DNA aptamers efficiently inhibit in vitro hemozoin formation catalyzed by either a model lipid system or parasite-derived extracts just as or more potently than chloroquine. Furthermore, when parasites are grown in red cells loaded with heme-binding aptamers, their growth is significantly inhibited relative to parasites exposed to non-heme-binding DNA oligonucleotides. Both the timing of parasite-induced toxicity and the concentration of heme-binding aptamer required for inducing toxicity correlate well with the uptake of red cell cytosolic components by the parasite, and the requirement for compounds with similar in vitro hemozoin inhibitory potency to preconcentrate within the parasite before observing toxicity. Thus, these heme-binding aptamers recapitulate the in vitro hemozoin inhibition activity and induce parasite toxicity in a manner consistent with inhibition of this pathway. Altogether, these data demonstrate that aptamers can be versatile tools with applicability in functionally dissecting important P. falciparum-specific pathways both in vitro and in vivo. PMID:19633187

  2. ROLE OF ETHYLENE IN NAPHTHALENE-MEDIATED SPROUT GROWTH INHIBITION IN POTATO

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A number of substituted naphthalenes reversibly inhibit potato (Solanum tuberosum L.) sprout growth and may have potential as commercial sprout inhibitors. Sprout growth is also reversibly inhibited by ethylene treatment and ethylene production is often stimulated by xenobiotics. The role of endog...

  3. Enantioselective Response of Rice and Barnyard Millet on Root Growth Inhibition by Optically Active ?-Methylbenzyl Phenylureas

    Microsoft Academic Search

    Hiroyoshi Omokawa; Jae Hwan Ryoo

    2001-01-01

    Optical active ?-methylbenzyl p-tolylureas (7, 8) show diverse plant physiological properties. Experiments were conducted to evaluate the response of the optically active ?-methylbenzyl phenylureas on root growth inhibition against rice and barnyard millet and to assess differential chiral responses of both plants from the viewpoints of activity, enantioselectivity, and cross intergenus response. A preference configuration to inhibit the root growth

  4. Compounds in a particular production lot of tryptic soy broth inhibit Staphylococcus aureus cell growth.

    PubMed

    Ishii, Masaki; Matsumoto, Yasuhiko; Sekimizu, Kazuhisa

    2015-01-01

    Staphylococcus aureus Newman strain and several methicillin-resistant S. aureus (MRSA) clinical isolates were grown on agar plates prepared with conventional lots of tryptic soy broth (TSB). Cell growth of these strains was inhibited on agar plates containing TSB of a particular product lot (lot A), whereas the cell growth of S. aureus RN4220 strain and several other MRSA clinical isolates was not inhibited. The cell growth of a strain of S. epidermidis was also inhibited on agar plates containing TSB of lot A, whereas the cell growth of Bacillus subtilis, Lactococcus lactis, Klebsiella pneumonia, Salmonella enterica, Serratia marcescens, Pseudomonas aeruginosa, and Escherichia coli was not inhibited. Although cell growth of the Newman strain was inhibited on agar plates containing TSB of lot A that was autoclaved in stainless steel or glass containers, cell growth inhibition was not observed when the medium was autoclaved in polypropylene containers. Compounds that inhibited the cell growth of the Newman strain were extracted from a polypropylene tube that was preincubated with liquid medium prepared from TSB of lot A. These findings suggest that polypropylene-binding compounds in TSB of lot A inhibited the cell growth of S. aureus Newman strain, some MRSA clinical isolates, and S. epidermidis. PMID:26193939

  5. Peroxisome proliferator-activated receptor ?-dependent and -independent growth inhibition of gastrointestinal tumour cells

    Microsoft Academic Search

    M. Azharul Karim Rumi; Shunji Ishihara; Yasunori Kadowaki; C. F. Ortega-Cava; Hideaki Kazumori; Kousaku Kawashima; Nagisa Yoshino; Takafumi Yuki; Norihisa Ishimura; Yoshikazu Kinoshita

    2004-01-01

    Peroxisome proliferator-activated receptor ? ? ? ? (PPAR? ? ? ? ) acts as a ligand-activated transcription factor. Although ligand-induced cellular differentiation and growth inhibition have been mostly studied on human cancers expressing PPAR? ? ? ? , it is unclear if the transcriptional activation of PPAR? ? ? ? is the main mechanism of growth inhibition. In this study,

  6. Photocatalytic Inhibition of Algae Growth Using TiO2, WO3, and

    E-print Network

    Ouellette, Anthony J. A.

    drag and additional fuel consumption. Excessive algae build-up can occlude drainage pipes and foulPhotocatalytic Inhibition of Algae Growth Using TiO2, WO3, and Cocatalyst Modifications C L O V I as photocatalytic surfacing agents to inhibit the attachment and growth of Oedogonium, a sessile, filamentous algae

  7. Ascorbic acid inhibits [3H]SCH-23390 binding to striatal dopamine D1 receptors.

    PubMed

    Wiener, H L; Lajtha, A; Sershen, H

    1989-01-01

    The present study describes the inhibition of [3H]SCH-23390 binding to striatal dopamine D1 receptors in the presence of ascorbic acid. Specific [3H]SCH-23390 binding was maximally inhibited by 0.1 mM ascorbic acid. As determined by Scatchard analysis the binding in the presence of 0.01, 0.1, or 10 mM ascorbic acid was consonant with non-competitive inhibition with a 26%, 38%, or 19% decrease, respectively, in the maximal number of binding sites; the affinity of these binding sites was not affected. Inhibition of [3H]SCH-23390 binding by ascorbic acid was reversible; striatal homogenates incubated with 0.1 mM ascorbic acid and subsequently washed free of ascorbic acid had the same Scatchard parameters as untreated preparations. PMID:2531799

  8. Quercetin induces HepG2 cell apoptosis by inhibiting fatty acid biosynthesis

    PubMed Central

    ZHAO, PENG; MAO, JUN-MIN; ZHANG, SHU-YUN; ZHOU, ZE-QUAN; TAN, YANG; ZHANG, YU

    2014-01-01

    Quercetin can inhibit the growth of cancer cells with the ability to act as a ‘chemopreventer’. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis, as well as its antioxidant functions. Quercetin can also reduce adipogenesis. Previous studies have shown that quercetin has potent inhibitory effects on animal fatty acid synthase (FASN). In the present study, activity of quercetin was evaluated in human liver cancer HepG2 cells. Intracellular FASN activity was calculated by measuring the absorption of NADPH via a spectrophotometer. MTT assay was used to test the cell viability, immunoblot analysis was performed to detect FASN expression levels and the apoptotic effect was detected by Hoechst 33258 staining. In the present study, it was found that quercetin could induce apoptosis in human liver cancer HepG2 cells with overexpression of FASN. This apoptosis was accompanied by the reduction of intracellular FASN activity and could be rescued by 25 or 50 ?M exogenous palmitic acids, the final product of FASN-catalyzed synthesis. These results suggested that the apoptosis induced by quercetin was via the inhibition of FASN. These findings suggested that quercetin may be useful for preventing human liver cancer. PMID:25009654

  9. Phellinus linteus extract induces autophagy and synergizes with 5-fluorouracil to inhibit breast cancer cell growth.

    PubMed

    Lee, Wen-Ying; Hsu, Keng-Fu; Chiang, Tai-An; Chen, Chee-Jen

    2015-01-01

    Phellinus linteus (PL) is a medicinal mushroom due to its several biological properties, including anticancer activity. However, the mechanisms of its anticancer effect remain to be elucidated. We evaluated the inhibitory effects of the ethanolic extract from the PL combined with 5-FU on MDA-MB-231 breast cancer cell line and to determine the mechanism of cell death. Individually, PL extract and 5-FU significantly inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner. PL extract (30 mg/mL) in combination with 5-FU (10 ?g/mL) synergistically inhibited MDA-MB-231 cells by 1.8-fold. PL did not induce apoptosis, as demonstrated by the DNA fragmentation assay, the sub-G1 population, and staining with annexin V-FITC and propidium iodide. The exposure of MDA-MB-231 cells to PL extracts resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine staining, the formation of acidic vesicular organelles, autophagosome membrane association of microtubule-associated protein light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, and ultrastructural observation of autophagic vacuoles by transmission electron microscopy. We concluded that PL extracts synergized with low doses of 5-FU to inhibit triple-negative breast cancer cell growth and demonstrated that PL extract can induce autophagy-related cell death. PMID:25622112

  10. The effects of colchicine and gibberellic acid on growth and microtubules in excised lettuce hypocotyls

    Microsoft Academic Search

    Deborah J. Durnam; Russell L. Jones

    1982-01-01

    The effect of colchicine on growth and microtubules in H2O-and gibberellic acid (GA3)-treated hypocotyls of lettuce (Lactuca sativa L. cv. Arctic) was examined. Hypocotyls of seedlings from ?-irradiated as well as non-irradiated seedlings were used in order to establish that the drug was affecting cell elongation and not cell division. Although colchicine inhibited elongation of GA3-treated hypocotyl sections at concentrations

  11. Effects of cadmium and salicylic acid on growth, spectral reflectance and photosynthesis of castor bean seedlings

    Microsoft Academic Search

    Caifeng Liu; Jiali Guo; Yanlan Cui; Tianfeng Lü; Xiaohuan Zhang; Gangrong Shi

    2011-01-01

    Salicylic acid (SA) is a potent signaling molecule in plants and is involved in eliciting specific responses to biotic and\\u000a abiotic stresses. The aim of this study is to investigate whether the exogenous application of SA can improve cadmium (Cd)\\u000a induced inhibition of photosynthesis in castor bean (Ricinus communis L.) plants. The effects of SA and Cd on plant growth,

  12. Inhibition of growth and aflatoxin production in Aspergillus parasiticus by essential oils of selected plant materials.

    PubMed

    Tantaoui-Elaraki, A; Beraoud, L

    1994-01-01

    We studied the effect of 13 chemically different essential oils (EO) on the mycelial growth of and aflatoxin synthesis by Aspergillus parasiticus. Cinnamon, thyme, oregano, and cumin EO were able to stop mycelial growth at only 0.1% in the medium, while curcumin, ginger, lemon, and orange EO were unable to inhibit totally the growth even at 1% concentration. Coriander, black pepper, mugwort, bay, and rosemary EO caused the growth to stop at concentrations between 0.2 and 1%. The EO most active upon mycelial growth were also the most active against aflatoxinogenesis. However, aflatoxin synthesis was inhibited by all the EO at higher extent than the mycelial growth. PMID:7823297

  13. Inhibition of benzoic acid on the polyaniline–polyphenol oxidase biosensor

    Microsoft Academic Search

    Shengqi Li; Yongyan Tan; Peng Wang; Jinqing Kan

    2010-01-01

    A polyaniline–polyphenol oxidase (PANI–PPO) biosensor for detecting benzoic acid is reported. The biosensor is based on the inhibition of benzoic acid on the biocatalytic activity of the polyphenol oxidase (PPO). The Michaelis–Menten constant (k?m) and maximum response current (Imax) in both the absence and presence of benzoic acid are also evaluated. The kinetic analyses show that the inhibition of benzoic

  14. Inhibition of Farnesoid X Receptor Controls Esophageal Cancer Cell Growth In Vitro and in Nude Mouse Xenografts

    PubMed Central

    Guan, Baoxiang; Li, Hao; Yang, Zhengduo; Hoque, Ashraful; Xu, Xiaochun

    2012-01-01

    BACKGROUND Gastroesophageal reflux is a risk factor for esophageal adenocarcinoma and bile acid and its farnesoid X receptor (FXR) have been implicated in esophageal tumorigenesis. We investigated the role of FXR expression and activity in esophageal cancer initiation and growth. METHODS FXR expression in esophageal adenocarcinoma tissues was assessed by immunohistochemistry. Knockdown of FXR expression in esophageal cancer cells in vitro and in nude mice xenografts was suppressed by FXR shRNA and guggulsterone (a natural FXR inhibitor). Esophageal cancer cells were treated with bile acids to show their effects on growth-promoting genes. RESULTS FXR was expressed in 48 of 59 esophageal adenocarcinoma tissues (81.3%), and this overexpression was associated with higher tumor grade, greater tumor size, and lymph node metastasis, but was inversely associated with RAR-?2 expression. Knockdown of FXR expression suppressed tumor cell growth in vitro and in nude mouse xenografts. Guggulsterone reduced viability of esophageal cancer cells in a time- and dose-dependent manner, whereas this effect was diminished after knockdown of FXR expression. Guggulsterone induced apoptosis through activation of caspases-8, -9, and -3 in tumor cells. FXR mediated bile acid–induced alterations of gene expression, e.g., RAR-?2 and COX-2. CONCLUSION Inhibition of FXR by FXR shRNA or guggulsterone suppressed tumor cell viability and induced apoptosis in vitro and reduced tumor formation and growth in nude mouse xenografts. FXR mediated bile acid–induced alterations of cell growth-related genes in esophageal cancer cells. PMID:23280144

  15. Inhibition of glycogen phosphorylase (GP) by CP91,149 induces growth inhibition correlating with brain GP expression

    Microsoft Academic Search

    Joachim B Schnier; Kayoko Nishi; Anne Monks; Fredric A Gorin; E. Morton Bradbury

    2003-01-01

    The role of glycogenolysis in normal and cancer cells was investigated by inhibiting glycogen phosphorylase (GP) with the synthetic inhibitor CP-91,149. A549 non-small cell lung carcinoma (NSCLC) cells express solely the brain isozyme of GP, which was inhibited by CP-91,149 with an IC50 of 0.5?M. When treated with CP-91,149, A549 cells accumulated glycogen with associated growth retardation. Treated normal skin

  16. Inhibition of Trypanosoma cruzi growth by medical plant extracts.

    PubMed

    Schinella, G R; Tournier, H A; Prieto, J M; Ríos, J L; Buschiazzo, H; Zaidenberg, A

    2002-12-01

    This study describes the screening of extracts obtained from 18 plants and two fungi used in the Chinese and Mediterranean traditional medicines on epimastigote forms of Trypanosoma cruzi. The extracts were tested against epimastigote of T. cruzi Bra C15C2 clone in vitro at 27 degrees C and at a concentration of 250 microg/ml in axenic culture. Angelica dahurica, A. pubescens, A. sinensis, Astragalus membranaceus, Coptis chinensis, Haplophyllum hispanicum, Phellodendron amurense, Poria cocos, Ranunculus sceleratus and Scutellaria baicalensis showed significant effects against the parasite with a percentage of growth inhibition between 20 and 100%. C. chinensis and R. sceleratus showed the greatest activity with IC(50) values of 1.7 microg/ml for C. chinensis and 10.7 microg/ml for R. sceleratus. These activities are greater than that of allopurinol. C. chinesis and R. sceleratus extracts did not show cytotoxic effects on rat polimorphonuclear cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactic dehydrogenase assays. These results allowed us to suggest that R. sceleratus and C. chinensis could be a source of new compounds clinically active against T. cruzi. PMID:12490214

  17. Inhibition of Smooth Muscle Proliferation by Urea-Based Alkanoic Acids via Peroxisome Proliferator-Activated

    E-print Network

    Hammock, Bruce D.

    Inhibition of Smooth Muscle Proliferation by Urea-Based Alkanoic Acids via Peroxisome Proliferator cell proliferation. We examined the possibility that urea-based alkanoic acids activate the nuclear--These results show that attenuation of smooth muscle cell proliferation by urea-based alkanoic acids is mediated

  18. Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability

    SciTech Connect

    Zhang, Jingjie [State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Haidian District, Beijing 100191 (China) [State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Haidian District, Beijing 100191 (China); Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States); Ouyang, Weiming; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui; Wang, York [Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States)] [Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States); Li, Xuejun, E-mail: xjli@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Haidian District, Beijing 100191 (China)] [State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Haidian District, Beijing 100191 (China); Huang, Chuanshu, E-mail: chuanshu.huang@nyumc.org [Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States)] [Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States)

    2012-09-01

    Suberoylanilide hydroxamic acid (SAHA) inhibiting cancer cell growth has been associated with its downregulation of cyclin D1 protein expression at transcription level or translation level. Here, we have demonstrated that SAHA inhibited EGF-induced Cl41 cell transformation via the decrease of cyclin D1 mRNA stability and induction of G0/G1 growth arrest. We found that SAHA treatment resulted in the dramatic inhibition of EGF-induced cell transformation, cyclin D1 protein expression and induction of G0/G1 growth arrest. Further studies showed that SAHA downregulation of cyclin D1 was only observed with endogenous cyclin D1, but not with reconstitutionally expressed cyclin D1 in the same cells, excluding the possibility of SAHA regulating cyclin D1 at level of protein degradation. Moreover, SAHA inhibited EGF-induced cyclin d1 mRNA level, whereas it did not show any inhibitory effect on cyclin D1 promoter-driven luciferase reporter activity under the same experimental conditions, suggesting that SAHA may decrease cyclin D1 mRNA stability. This notion was supported by the results that treatment of cells with SAHA decreased the half-life of cyclin D1 mRNA from 6.95 h to 2.57 h. Consistent with downregulation of cyclin D1 mRNA stability, SAHA treatment also attenuated HuR expression, which has been well-characterized as a positive regulator of cyclin D1 mRNA stability. Thus, our study identifies a novel mechanism responsible for SAHA inhibiting cell transformation via decreasing cyclin D1 mRNA stability and induction of G0/G1 growth arrest in Cl41 cells. -- Highlights: ? SAHA inhibits cell transformation in Cl41 cells. ? SAHA suppresses Cyclin D1 protein expression. ? SAHA decreases cyclin D1 mRNA stability.

  19. UV photolysis for relieved inhibition of sulfadiazine (SD) to biomass growth.

    PubMed

    Pan, Shihui; Yan, Ning; Zhang, Yongming; Rittmann, Bruce E

    2015-05-01

    UV photolysis was used to relieve inhibition of biomass growth by sulfadiazine (SD), a broad-spectrum anti-microbial. To investigate the effects of SD on biomass growth, three substrates-glucose alone (G), glucose plus sulfadiazine (G+SD), and glucose plus photolyzed SD (G+PSD)-were used to culture the bacteria acclimated to glucose. The biomass was strongly inhibited when SD was added into the glucose solution, but inhibition was relieved to a significant degree when the SD was treated with UV irradiation as a pretreatment. The biomass growth kinetics were described well by the Monod model when glucose was used as a substrate alone, but the kinetics followed a hybrid Aiba model for non-competitive inhibition when SD was added to the solution. When photolyzed SD was added to glucose solution to replace original SD, the growth still followed Aiba inhibition, but inhibition was significantly relieved: the maximum specific growth rate (? max) increased by 17 %, and the Aiba inhibition concentration increased by 60 %. Aniline, a major product of UV photolysis, supported the growth of the glucose-biodegrading bacteria. Thus, UV photolysis of SD significantly relieved inhibition by lowering the SD concentration and by generating a biodegradable product. PMID:25533040

  20. Effect of acidic seed on biogenic secondary organic aerosol growth

    NASA Astrophysics Data System (ADS)

    Czoschke, Nadine M.; Jang, Myoseon; Kamens, Richard M.

    Secondary organic aerosol (SOA) growth in the presence of acid aerosols was studied in twin 500 l Teflon bags and in a 4 m flow reactor. In Teflon bags, isoprene, acrolein and ?-pinene were all made to react individually with ozone and exposed to either acid or non-acid inorganic seed aerosols to determine the effect of acid-catalyzed heterogeneous reactions on SOA growth. ?-Pinene and ozone were made to react in a flow reactor to assess the immediate effect of mixing an acid aerosol with SOA at high and low relative humidity levels. In all cases, exposure to acid seed aerosol increased the amount of SOA mass produced. Fourier transform infrared spectra of the SOA in acid systems confirmed the transformation of carbonyl functional groups through acid-catalyzed heterogeneous reactions when SOAs formed in acidic environments or were exposed to acidic aerosols. Organic products initially produced from ozonation in the gas phase partition onto the inorganic seed aerosol and react heterogeneously with an acid catalyst forming low vapor pressure products. These acid-catalyzed heterogeneous reactions are implicated in generating the increased SOA mass observed in acidic aerosol systems as they transform predominantly gas phase compounds of high volatility into low vapor pressure predominantly particle phase products.

  1. Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits

    PubMed Central

    Verheul, H M W; Panigrahy, D; Yuan, J; D'Amato, R J

    1999-01-01

    Neovascularization facilitates tumour growth and metastasis formation. In our laboratory, we attempt to identify clinically available oral efficacious drugs for antiangiogenic activity. Here, we report which non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit corneal neovascularization, induced by basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF). This antiangiogenic activity may contribute to the known effects of NSAIDs on gastric ulcers, polyps and tumours. We found that sulindac was one of the most potent antiangiogenic NSAIDs, inhibiting bFGF-induced neovascularization by 50% and VEGF-induced neovascularization by 55%. Previously, we reported that thalidomide inhibited growth factor-induced corneal neovascularization. When we combined sulindac with thalidomide, we found a significantly increased inhibition of bFGF- or VEGF-induced corneal neovascularization (by 63% or 74% respectively) compared with either agent alone (P< 0.01). Because of this strong antiangiogenic effect, we tested the oral combination of thalidomide and sulindac for its ability to inhibit the growth of V2 carcinoma in rabbits. Oral treatment of thalidomide or sulindac alone inhibited tumour growth by 55% and 35% respectively. When given together, the growth of the V2 carcinoma was inhibited by 75%. Our results indicated that oral antiangiogenic combination therapy with thalidomide and sulindac may be a useful non-toxic treatment for cancer. © 1999 Cancer Research Campaign PMID:10408702

  2. Development of poly(aspartic acid-co-malic acid) composites for calcium carbonate and sulphate scale inhibition.

    PubMed

    Mithil Kumar, N; Gupta, Sanjay Kumar; Jagadeesh, Dani; Kanny, K; Bux, F

    2015-05-01

    Polyaspartic acid (PSI) is suitable for the inhibition of inorganic scale deposition. To enhance its scale inhibition efficiency, PSI was modified by reacting aspartic acid with malic acid (MA) using thermal polycondensation polymerization. This reaction resulted in poly(aspartic acid-co-malic acid) (PSI-co-MA) dual polymer. The structural, chemical and thermal properties of the dual polymers were analysed by using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and gel permeation chromatography. The effectiveness of six different molar ratios of PSI-co-MA dual polymer for calcium carbonate and calcium sulphate scale inhibition at laboratory scale batch experiments was evaluated with synthetic brine solution at selected doses of polymer at 65-70°C by the static scale test method. The performance of PSI-co-MA dual polymer for the inhibition of calcium carbonate and calcium sulphate precipitation was compared with that of a PSI single polymer. The PSI-co-MA exhibited excellent ability to control inorganic minerals, with approximately 85.36% calcium carbonate inhibition and 100% calcium sulphate inhibition at a level of 10?mg/L PSI-co-MA, respectively. Therefore, it may be reasonably concluded that PSI-co-MA is a highly effective scale inhibitor for cooling water treatment applications. PMID:25371160

  3. Escherichia coli Mutants Thermosensitive for Deoxyribonucleic Acid Gyrase Subunit A: Effects on Deoxyribonucleic Acid Replication, Transcription, and Bacteriophage Growth

    PubMed Central

    Kreuzer, Kenneth N.; Cozzarelli, Nicholas R.

    1979-01-01

    Temperature-sensitive nalA mutants of Escherichia coli have been used to investigate the structure and functions of deoxyribonucleic acid (DNA) gyrase. Extracts of one such mutant (nalA43) had thermosensitive DNA gyrase subunit A activity but normal gyrase subunit B activity, proving definitively that nalA is the structural gene for subunit A. Extracts of a second nalA (Ts) mutant (nalA45) had a 50-fold deficiency of gyrase subunit A activity. The residual DNA supertwisting was catalyzed by the mutant DNA gyrase rather than by a novel supertwisting enzyme. The nalA45(Ts) extract was also deficient in the nalidixic acid target, which is defined as the protein necessary to confer drug sensitivity to in vitro DNA replication directed by a nalidixic acid-resistant mutant extract. Thus, gyrase subunit A and the nalidixic acid target are one and the same protein, the nalA gene product. Shift of the nalA43(Ts) mutant to a nonpermissive temperature resulted in a precipitous decline in the rate of [3H]thymidine incorporation, demonstrating an obligatory role of the nalA gene product in DNA replication. The rates of incorporation of [3H]uridine pulses and continuously administered [3H]uracil were quickly reduced approximately twofold upon temperature shift of the nalA43(Ts) mutant, and therefore some but not all transcription requires the nalA gene product. The thermosensitive growth of bacteriophages ?X174 and T4 in the nalA43(Ts) host shows that these phages depend on the host nalA gene product. In contrast, the growth of phage T7 was strongly inhibited by nalidixic acid but essentially unaffected by the nalA43(Ts) mutation. The inhibition of T7 growth by nalidixic acid was, however, eliminated by temperature inactivation of the nal43 gene product. Therefore, nalidixic acid may block T7 growth by a corruption rather than a simple elimination of the nalidixic acid target. Possible mechanisms for such a corruption are considered, and their relevance to the puzzling dominance of drug sensitivity is discussed. Images PMID:227840

  4. Inhibition of Hyaluronan Synthase-3 Decreases Subcutaneous Colon Cancer Growth by Increasing Apoptosis

    PubMed Central

    Teng, Brian P.; Heffler, Melissa D.; Lai, Eric C.; Zhao, Ya-Li; LeVea, Charles M.; Golubovskaya, Vita M.; Dunn, Kelli M. Bullard

    2012-01-01

    Hyaluronan (HA) and hyaluronan synthases (HAS) have been implicated in cancer growth and progression. We previously have shown that HAS3 and HA mediate tumor growth in SW620 colon cancer cells, but the mechanism remains poorly understood. In addition, the effect of HAS3 inhibition on tumor growth with other cells lines has not been explored. We therefore hypothesized that inhibition of HAS3 in highly tumorigenic HCT116 colon cancer cells would decrease tumor growth and that the underlying mechanism would involve altering proliferation and/or apoptosis. HAS3 expression was inhibited by transfection with siRNA; a scrambled sequence served as a control. Stable transfectants were injected into the flanks of nude mice and tumor growth followed for 30 days. Proliferation and apoptosis were then assessed in the harvested tumors. Results were compared using the Students’ t-test and ANOVA where appropriate. siRNA transfection decreased HAS3 expression, protein production, and pericellular HA retention, and decreased in vivo tumor growth. Proliferation was unaffected in the HCT116 tumors, but increased slightly in the SW620 tumors. In contrast, HAS3 inhibition significantly increased apoptosis in all tumors. HAS3 inhibition decreases subcutaneous tumor growth by colon cancer cells and significantly increases apoptosis with less effect on proliferation. These data show that HAS3 and HA mediate colon cancer growth by inhibiting apoptosis. PMID:21453239

  5. [Combined injured effects of acid rain and lanthanum on growth of soybean seedling].

    PubMed

    Liang, Chan-juan; Pan, Dan-yun; Xu, Qiu-rong; Zhou, Qing

    2010-07-01

    Combined effects of acid rain and lanthanum on growth of soybean seedling (Glycine max) and its inherent mechanism were studied in this paper. Compared with treatments by simulated acid rain (pH 3.0, 3.5, 4.5) or rare earth La(III) (60, 100 and 300 mg x L(-1)), the decrease degree of growth parameters in combined treatments was higher, indicating that there were a synergistic effects between acid rain and La. Moreover,the inhibition effects of acid rain and La(III) were more obvious when pH value of acid rain was lower or the concentration of La(III) was higher. The changes of photosynthetic parameters were similar to those of growth, but the decrease degree of each parameter was not same in the same treatment group. The decrease degree of optimal PSII photochemical efficiency (Fv/Fm) and chlorophyll content (Chl) were 9.35%-22.75% and 9.14%-24.53%, respectively, lower than that of photosynthetic rate Pn (22.78%-84.7%), Hill reaction rate (15.52%-73.38%) and Mg2+ -ATPase activity (14.51%-71.54%), showing that the sensitivity of photosynthetic parameters to the combined factors was different. Furthermore, relative analysis showed that the change of Pn were mainly affected by Hill reaction rate and Mg2+ -ATPase activity, and was less influenced by Chl and Fv/Fm. It indicates that the effect of acid rain and La on each reaction in photosynthesis was different, and the inhibition of combined treatments on photosynthesis in plants was one of the main factors affecting growth of plant. PMID:20825040

  6. Inhibition by diacylmethane derivatives of mutagenicity and nucleic acid binding of 2-aminofluorene derivatives.

    PubMed

    Wang, C Y; Lee, M S; Nagase, H; Zukowski, K

    1989-11-15

    The active methylene compounds acetylacetone, 1,1,1-trifluoroacetylacetone, benzoylacetone, dibenzoylmethane, and 1,3-indandione inhibited the mutagenicity of 2-nitrofluorene in Salmonella typhimurium. They also inhibited the N,O-acetyltransferase-catalyzed transfer RNA binding of N-hydroxy-2-acetylaminofluorene, but they did not inhibit N,O-acetyltransferase. However, only 1,3-indandione and 1,1,1-trifluoroacetylacetone significantly inhibited the binding of N-acetoxy-2-acetylaminofluorene to transfer RNA. Reaction of the trifluoro compound with the acetoxy compound yielded 1-(N-2-fluorenylacetamido)acetone. These results demonstrate that active methylene compounds can inhibit mutagenicity and nucleic acid binding of chemical carcinogens. PMID:2681797

  7. Mechanism of inhibition caused by long-chain fatty acids in anaerobic digestion process

    SciTech Connect

    Hanaki, K.; Matsuo, T.; Nagase, M.

    1981-07-01

    The inhibitory effect of long-chain fatty acids on the anaerobic digestion process was examined in batch experiments using synthetic substrates. The addition of long-chain fatty acids caused the appearance of the lag period in the methane production from acetate and in the degradation of both long-chain fatty acids and n-butyrate. Methane production from hydrogen proceeded without lag period although its rate was lowered. Fermentation of glucose was not inhibited. Neutral fat in the whole milk was easily hydrolyzed to long-chain fatty acids, which brought about the inhibition. The addition of calcium chloride reduced the inhibitory effect of long-chain fatty acids, but it did not do so after the culture had been exposed to long-chain fatty acids for more than several hours. The addition of calcium carbonate could not reduce the inhibition because of its insolubility. (Refs. 18).

  8. Inhibition of fumarase by bismuth(III): implications for the tricarboxylic acid cycle as a potential target of bismuth drugs in Helicobacter pylori

    Microsoft Academic Search

    Zhuo Chen; Qinglu Zhou; Ruiguang Ge

    Helicobacter pylori causes various gastric diseases, such as gastritis, peptic ulcerations and gastric cancer. Triple therapy combining bismuth\\u000a compounds with two antibiotics is the cornerstone of the treatment of H. pylori infections. Up to now, the molecular mechanisms by which bismuth inhibits the growth of H. pylori are far from clear. In the bacterial tricarboxylic acid (TCA) cycle, fumarase catalyses

  9. A Microplate Growth Inhibition Assay for Screening Bacteriocins against Listeria monocytogenes to Differentiate Their Mode-of-Action.

    PubMed

    Vijayakumar, Paul Priyesh; Muriana, Peter M

    2015-01-01

    Lactic acid bacteria (LAB) have historically been used in food fermentations to preserve foods and are generally-recognized-as-safe (GRAS) by the FDA for use as food ingredients. In addition to lactic acid; some strains also produce bacteriocins that have been proposed for use as food preservatives. In this study we examined the inhibition of Listeria monocytogenes 39-2 by neutralized and non-neutralized bacteriocin preparations (Bac+ preps) produced by Lactobacillus curvatus FS47; Lb. curvatus Beef3; Pediococcus acidilactici Bac3; Lactococcus lactis FLS1; Enterococcus faecium FS56-1; and Enterococcus thailandicus FS92. Activity differences between non-neutralized and neutralized Bac+ preps in agar spot assays could not readily be attributed to acid because a bacteriocin-negative control strain was not inhibitory to Listeria in these assays. When neutralized and non-neutralized Bac+ preps were used in microplate growth inhibition assays against L. monocytogenes 39-2 we observed some differences attributed to acid inhibition. A microplate growth inhibition assay was used to compare inhibitory reactions of wild-type and bacteriocin-resistant variants of L. monocytogenes to differentiate bacteriocins with different modes-of-action (MOA) whereby curvaticins FS47 and Beef3, and pediocin Bac3 were categorized to be in MOA1; enterocins FS92 and FS56-1 in MOA2; and lacticin FLS1 in MOA3. The microplate bacteriocin MOA assay establishes a platform to evaluate the best combination of bacteriocin preparations for use in food applications as biopreservatives against L. monocytogenes. PMID:26111195

  10. A Microplate Growth Inhibition Assay for Screening Bacteriocins against Listeria monocytogenes to Differentiate Their Mode-of-Action

    PubMed Central

    Vijayakumar, Paul Priyesh; Muriana, Peter M.

    2015-01-01

    Lactic acid bacteria (LAB) have historically been used in food fermentations to preserve foods and are generally-recognized-as-safe (GRAS) by the FDA for use as food ingredients. In addition to lactic acid; some strains also produce bacteriocins that have been proposed for use as food preservatives. In this study we examined the inhibition of Listeria monocytogenes 39-2 by neutralized and non-neutralized bacteriocin preparations (Bac+ preps) produced by Lactobacillus curvatus FS47; Lb. curvatus Beef3; Pediococcus acidilactici Bac3; Lactococcus lactis FLS1; Enterococcus faecium FS56-1; and Enterococcus thailandicus FS92. Activity differences between non-neutralized and neutralized Bac+ preps in agar spot assays could not readily be attributed to acid because a bacteriocin-negative control strain was not inhibitory to Listeria in these assays. When neutralized and non-neutralized Bac+ preps were used in microplate growth inhibition assays against L. monocytogenes 39-2 we observed some differences attributed to acid inhibition. A microplate growth inhibition assay was used to compare inhibitory reactions of wild-type and bacteriocin-resistant variants of L. monocytogenes to differentiate bacteriocins with different modes-of-action (MOA) whereby curvaticins FS47 and Beef3, and pediocin Bac3 were categorized to be in MOA1; enterocins FS92 and FS56-1 in MOA2; and lacticin FLS1 in MOA3. The microplate bacteriocin MOA assay establishes a platform to evaluate the best combination of bacteriocin preparations for use in food applications as biopreservatives against L. monocytogenes. PMID:26111195

  11. A Microplate Growth Inhibition Assay for Screening Bacteriocins against Listeria monocytogenes to Differentiate Their Mode-of-Action.

    PubMed

    Vijayakumar, Paul Priyesh; Muriana, Peter M

    2015-01-01

    Lactic acid bacteria (LAB) have historically been used in food fermentations to preserve foods and are generally-recognized-as-safe (GRAS) by the FDA for use as food ingredients. In addition to lactic acid; some strains also produce bacteriocins that have been proposed for use as food preservatives. In this study we examined the inhibition of Listeria monocytogenes 39-2 by neutralized and non-neutralized bacteriocin preparations (Bac? preps) produced by Lactobacillus curvatus FS47; Lb. curvatus Beef3; Pediococcus acidilactici Bac3; Lactococcus lactis FLS1; Enterococcus faecium FS56-1; and Enterococcus thailandicus FS92. Activity differences between non-neutralized and neutralized Bac? preps in agar spot assays could not readily be attributed to acid because a bacteriocin-negative control strain was not inhibitory to Listeria in these assays. When neutralized and non-neutralized Bac? preps were used in microplate growth inhibition assays against L. monocytogenes 39-2 we observed some differences attributed to acid inhibition. A microplate growth inhibition assay was used to compare inhibitory reactions of wild-type and bacteriocin-resistant variants of L. monocytogenes to differentiate bacteriocins with different modes-of-action (MOA) whereby curvaticins FS47 and Beef3, and pediocin Bac3 were categorized to be in MOA1; enterocins FS92 and FS56-1 in MOA2; and lacticin FLS1 in MOA3. The microplate bacteriocin MOA assay establishes a platform to evaluate the best combination of bacteriocin preparations for use in food applications as biopreservatives against L. monocytogenes. PMID:26117855

  12. Inhibition of glycogen phosphorylase (GP) by CP-91,149 induces growth inhibition correlating with brain GP expression.

    PubMed

    Schnier, Joachim B; Nishi, Kayoko; Monks, Anne; Gorin, Fredric A; Bradbury, E Morton

    2003-09-12

    The role of glycogenolysis in normal and cancer cells was investigated by inhibiting glycogen phosphorylase (GP) with the synthetic inhibitor CP-91,149. A549 non-small cell lung carcinoma (NSCLC) cells express solely the brain isozyme of GP, which was inhibited by CP-91,149 with an IC(50) of 0.5 microM. When treated with CP-91,149, A549 cells accumulated glycogen with associated growth retardation. Treated normal skin fibroblasts also accumulated glycogen with G1-cell cycle arrest that was associated with inhibition of cyclin E-CDK2 activity. Overall, cells expressing high levels of brain GP were growth inhibited by CP-91,149 correlating with glycogen accumulation whereas cells expressing low levels of brain GP were not affected by the drug. Analyses of 59 tumor cell lines represented in the NCI drug screen identified that every cell line expressed brain GP but the profile was dominated by a few highly GP expressing cell lines with lower than mean GP-a enzymatic activities. The correlation program, COMPARE, identified that the brain GP protein measured in the NCI cell lines corresponded with brain GP mRNA expression, ADP-ribosyltransferase 3, and colony stimulating factor 2 receptor alpha in the 10,000 gene microarray database with similar correlation coefficients. These results suggest that brain GP is present in proliferating cells and that high protein levels correspond with the ability of CP-91,149 to inhibit cell growth. PMID:12943673

  13. Changes in free amino acid, phenolic, chlorophyll, carotenoid, and glycoalkaloid contents in tomatoes during 11 stages of growth and inhibition of cervical and lung human cancer cells by green tomato extracts.

    PubMed

    Choi, Suk-Hyun; Lee, Sang-Hwa; Kim, Hyun-Jeong; Lee, In-Seon; Kozukue, Nobuyuki; Levin, Carol E; Friedman, Mendel

    2010-07-14

    Tomato ( Solanum lycopersicum ) plants synthesize nutrients, pigments, and secondary metabolites that benefit nutrition and human health. The concentrations of these compounds are strongly influenced by the maturity of the tomato fruit on the vine. Widely consumed Korean tomatoes of the variety Doturakworld were analyzed for changes in the content of free amino acids, phenolic compounds, chlorophylls, carotenoids, and glycoalkaloids at 11 stages (S1-S11) of ripeness. The results show that (a) the total content (in mg/100 g of FW) of the free amino acids and other nitrogen-containing compounds in the extracts ranged from about 41 to 85 in the green tomato extracts S1-S7 and then increased to 251 (S9) in the red extracts, followed by a decrease to 124 in S11 red extracts; (b) the total initial concentration and composition of up to 12 phenolic compounds of approximately 2000 microg/100 g of FW varied throughout the ripening process, with the quantity decreasing and the number of individual compounds increasing in the red tomato; (c) chlorophyll a and b content of tomatoes harvested during S1 was 5.73 mg/100 g of fresh pericarp and then decreased continuously to 1.14 mg/100 g for S11; (d) the concentration (in mg/100 g of FW) of lycopene in the S8 red extract of 0.32 increased to 1.27 in S11; and (e) tomatoes harvested during S1 contained 48.2 mg of dehydrotomatine/100 g of FW, and this value continually decreased to 1.5 in S7, with no detectable levels in S8-S11. The corresponding alpha-tomatine content decreased from S1 (361) to S8 (13.8). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell assay IC(50) values showed that Hel299 lung cells, A549 lung cancer cells, and HeLa cervical carcinoma cells were highly susceptible to inactivation by glycoalkaloid-rich green tomato extracts. Chang normal liver cells and U937 lymphoma cells were less susceptible. The possible significance of the results for plant physiology and the diet is discussed. PMID:20560602

  14. Effect of fusaric acid and phytoanticipins on growth of rhizobacteria and Fusarium oxysporum.

    PubMed

    Landa, Blanca B; Cachinero-Díaz, Juana M; Lemanceau, Philippe; Jiménez-Díaz, Rafael M; Alabouvette, Claude

    2002-11-01

    Suppression of soilborne diseases by biocontrol agents involves complex interactions among biocontrol agents and the pathogen and between these microorganisms and the plant. In general, these interactions are not well characterized. In this work, we studied (i) the diversity among strains of fluorescent Pseudomonas spp., Bacillus spp., and Paenibacillus sp. for their sensitivity to fusaric acid (FAc) and phytoanticipins from different host plants, (ii) the diversity of pathogenic and nonpathogenic Fusarium oxysporum isolates for their sensitivity to phytoanticipins, and (iii) the influence of FAc on the production of pyoverdine by fluorescent Pseudomonas spp. tolerant to this compound. There was a great diversity in the response of the bacterial strains to FAc; however, as a group, Bacillus spp. and Paenibacillus macerans were much more sensitive to FAc than Pseudomonas spp. FAc also affected production of pyoverdine by FAc-tolerant Pseudomonas spp. strains. Phytoanticipins differed in their effects on microbial growth, and sensitivity to a phytoanticipin varied among bacterial and fungal strains. Biochanin A did not affect growth of bacteria, but coumarin inhibited growth of Pseudomonas spp. strains and had no effect on Bacillus circulans and P. macerans. Conversely, tomatine inhibited growth of B. circulans and P. macerans. Biochanin A and tomatine inhibited growth of three pathogenic isolates of F. oxysporum but increased growth of three nonpathogenic F. oxysporum isolates. Coumarin inhibited growth of all pathogenic and nonpathogenic F. oxysporum isolates. These results are indicative of the complex interactions that can occur among plants, pathogens, and biological control agents in the rhizosphere and on the root surface. Also, these results may help to explain the low efficacy of some combinations of biocontrol agents, as well as the inconsistency in achieving disease suppression under field conditions. PMID:12556125

  15. Cytokinin Antagonizes Abscisic Acid-Mediated Inhibition of Cotyledon Greening by Promoting the Degradation of ABSCISIC ACID INSENSITIVE5 Protein in Arabidopsis1[C][W

    PubMed Central

    Guan, Chunmei; Wang, Xingchun; Feng, Jian; Hong, Sulei; Liang, Yan; Ren, Bo; Zuo, Jianru

    2014-01-01

    In higher plants, seed germination is followed by postgerminative growth. One of the key developmental events during postgerminative growth is cotyledon greening, which enables a seedling to establish photosynthetic capacity. The plant phytohormone abscisic acid (ABA) plays a vital role by inhibiting seed germination and postgerminative growth in response to dynamically changing internal and environmental cues. It has been shown that ABSCISIC ACID INSENSITIVE5 (ABI5), a basic leucine zipper transcription factor, is an important factor in the regulation of the ABA-mediated inhibitory effect on seed germination and postgerminative growth. Conversely, the phytohormone cytokinin has been proposed to promote seed germination by antagonizing the ABA-mediated inhibitory effect. However, the underpinning molecular mechanism of cytokinin-repressed ABA signaling is largely unknown. Here, we show that cytokinin specifically antagonizes ABA-mediated inhibition of cotyledon greening with minimal effects on seed germination in Arabidopsis (Arabidopsis thaliana). We found that the cytokinin-antagonized ABA effect is dependent on a functional cytokinin signaling pathway, mainly involved in the cytokinin receptor gene CYTOKININ RESPONSE1/ARABIDOPSIS HISTIDINE KINASE4, downstream histidine phosphotransfer protein genes AHP2, AHP3, and AHP5, and a type B response regulator gene, ARR12, which genetically acts upstream of ABI5 to regulate cotyledon greening. Cytokinin has no apparent effect on the transcription of ABI5. However, cytokinin efficiently promotes the proteasomal degradation of ABI5 in a cytokinin signaling-dependent manner. These results define a genetic pathway through which cytokinin specifically induces the degradation of ABI5 protein, thereby antagonizing ABA-mediated inhibition of postgerminative growth. PMID:24443524

  16. Inhibition of endometrial cancer by n-3 polyunsaturated fatty acids in preclinical models.

    PubMed

    Zheng, Hang; Tang, Hongjun; Liu, Miao; He, Minhong; Lai, Pinglin; Dong, Heling; Lin, Jun; Jia, Chunhong; Zhong, Mei; Dai, Yifan; Bai, Xiaochun; Wang, Liping

    2014-08-01

    Although preclinical and epidemiologic studies have shown the importance of n-3 polyunsaturated fatty acids (PUFA) in the prevention of hormone-responsive cancers such as breast cancer, evidence of the association between n-3 PUFAs and endometrial cancer risk is limited and no previous study has examined the effect of n-3 PUFAs on endometrial cancer in cellular and animal models. In this study, we demonstrated that docosahexenoic acid (DHA) dose- and time-dependently inhibited endometrial cancer cell proliferation, colony formation, and migration and promoted apoptosis. Dietary n-3 PUFAs efficiently prevented endometrial cancer cell growth in xenograft models. Moreover, ectopic expression of fat-1, a desaturase, catalyzed the conversion of n-6 to n-3 PUFAs and produced n-3 PUFAs endogenously, also suppressed endometrial tumor cell growth and migration, and potentiated apoptosis in endometrial cancer cell lines. Interestingly, implanted endometrial cancer cells were unable to grow in fat-1 transgenic SCID mice. Further study revealed that mTOR signaling, which plays an essential role in cell proliferation and endometrial tumorigenesis, is a target of n-3 PUFAs. Exogenous or endogenous n-3 PUFAs efficiently suppressed both mTOR complex 1 (mTORC1) and mTORC2 in vitro and in vivo. Moreover, both dietary n-3 PUFAs and transgenic expression of fat-1 in mice effectively repressed mTORC1/2 signaling and endometrial growth elicited by unopposed estrogen. Taken together, our findings provide comprehensive preclinical evidences that n-3 PUFAs efficiently prevent endometrial cancer and establish mTORC1/2 as a target of n-3 PUFAs. PMID:24866178

  17. Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma

    PubMed Central

    Subramani, Ramadevi; Lopez-Valdez, Rebecca; Salcido, Alyssa; Boopalan, Thiyagarajan; Arumugam, Arunkumar; Nandy, Sushmita; Lakshmanaswamy, Rajkumar

    2014-01-01

    Pancreatic cancer is the only major cancer with very low survival rates (1%). It is the fourth leading cause of cancer-related death. Hyperactivated growth hormone receptor (GHR) levels have been shown to increase the risk of cancer in general and this pathway is a master regulator of key cellular functions like proliferation, apoptosis, differentiation, metastasis, etc. However, to date there is no available data on how GHR promotes pancreatic cancer pathogenesis. Here, we used an RNA interference approach targeted to GHR to determine whether targeting GHR is an effective method for controlling pancreatic cancer growth and metastasis. For this, we used an in vitro model system consisting of HPAC and PANC-1 pancreatic cancer cells lines. GHR is upregulated in both of these cell lines and silencing GHR significantly reduced cell proliferation and viability. Inhibition of GHR also reduced the metastatic potential of pancreatic cancer cells, which was aided through decreased colony-forming ability and reduced invasiveness. Flow cytometric and western blot analyses revealed the induction of apoptosis in GHR silenced cells. GHR silencing affected phosphatidylinositol 3 kinase/AKT, mitogen extracellular signal-regulated kinase/extracellular signal-regulated kinase, Janus kinase/signal transducers and activators of transcription and mammalian target of rapamycin signaling, as well as, epithelial to mesenchymal transition. Interestingly, silencing GHR also suppressed the expression of insulin receptor-? and cyclo-oxygenease-2. Altogether, GHR silencing controls the growth and metastasis of pancreatic cancer and reveals its importance in pancreatic cancer pathogenesis. PMID:25301264

  18. Adaptive growth responses of Listeria monocytogenes to acid and osmotic shifts above and across the growth boundaries.

    PubMed

    Belessi, C-I A; Le Marc, Y; Merkouri, S I; Gounadaki, A S; Schvartzman, S; Jordan, K; Drosinos, E H; Skandamis, P N

    2011-01-01

    The effect of acid and osmotic shifts on the growth of Listeria monocytogenes was evaluated at 10°C. Two types of shifts were tested: (i) within the range of pH and water activity (a(w)) levels that allow growth of L. monocytogenes and (ii) after habituation at no-growth conditions back to growth-permitting conditions. A L. monocytogenes cheese isolate, with high survival capacity during cheesemaking, was inoculated (10(2) CFU/ml) in tryptic soy broth supplemented with 0.6% yeast extract at six pH levels (5.1 to 7.2; adjusted with lactic acid) and 0.5% NaCl (a(w) 0.995), or four a(w) levels (0.995 to 0.93, adjusted with 0.5 to 10.5% NaCl) at pH 7.2 and grown to early stationary phase. L. monocytogenes was then shifted (at 10(2) CFU/ml) to each of the aforementioned growth-permitting pH and a(w) levels and incubated at 10°C. Shifts from no-growth to growth-permitting conditions were carried out by transferring L. monocytogenes habituated at pH 4.9 or a(w) 0.90 (12.5% NaCl) for 1, 5, and 10 days to all pH and a(w) levels permitting growth. Reducing a(w) or pH at different levels in the range of 0.995 to 0.93 and 7.2 to 5.1, respectively, decreased the maximum specific growth rate of L. monocytogenes. The lag time of the organism increased with all osmotic downshifts, as well as by the reduction of pH to 5.1. Conversely, any type of shift within pH 5.5 to 7.2 did not markedly affect the lag times of L. monocytogenes. The longer the cells were incubated at no-growth a(w) (0.90), the faster they initiated growth subsequently, suggesting adaptation to osmotic stress. Conversely, extended habituation at pH 4.9 had the opposite effect on subsequent growth of L. monocytogenes, possibly due to cell injury. These results suggest that there is an adaptation or injury rate induced at conditions inhibiting the growth of the pathogen. Thus, quantifying adaptation phenomena under growth-limiting environments, such as in fermented dairy and meat products or products preserved in brine, is essential for reliable growth simulations of L monocytogenes during transportation and storage of foods. PMID:21219765

  19. Inhibition of Insulin and T 3 Induced Fatty Acid Synthase by Hexanoate

    Microsoft Academic Search

    Murielle M. Akpa; Sabine Sawadogo; Anne Radenne; Catherine Mounier

    2010-01-01

    Fatty acid synthase (FAS) is responsible for the de novo synthesis of palmitate and stearate. This enzyme is activated by\\u000a insulin and T3, and inhibited by fatty acids. In this study, we show that insulin and T3 have an inducing effect on FAS enzymatic activity, which is synergetic when both hormones are present. Octanoate and hexanoate\\u000a specifically inhibit this hormonal

  20. Dynamic Adaption of Metabolic Pathways during Germination and Growth of Lily Pollen Tubes after Inhibition of the Electron Transport Chain1[W][OPEN

    PubMed Central

    Obermeyer, Gerhard; Fragner, Lena; Lang, Veronika; Weckwerth, Wolfram

    2013-01-01

    Investigation of the metabolome and the transcriptome of pollen of lily (Lilium longiflorum) gave a comprehensive overview of metabolic pathways active during pollen germination and tube growth. More than 100 different metabolites were determined simultaneously by gas chromatography coupled to mass spectrometry, and expressed genes of selected metabolic pathways were identified by next-generation sequencing of lily pollen transcripts. The time-dependent changes in metabolite abundances, as well as the changes after inhibition of the mitochondrial electron transport chain, revealed a fast and dynamic adaption of the metabolic pathways in the range of minutes. The metabolic state prior to pollen germination differed clearly from the metabolic state during pollen tube growth, as indicated by principal component analysis of all detected metabolites and by detailed observation of individual metabolites. For instance, the amount of sucrose increased during the first 60 minutes of pollen culture but decreased during tube growth, while glucose and fructose showed the opposite behavior. Glycolysis, tricarbonic acid cycle, glyoxylate cycle, starch, and fatty acid degradation were activated, providing energy during pollen germination and tube growth. Inhibition of the mitochondrial electron transport chain by antimycin A resulted in an immediate production of ethanol and a fast rearrangement of metabolic pathways, which correlated with changes in the amounts of the majority of identified metabolites, e.g. a rapid increase in ?-aminobutyric acid indicated the activation of a ?-aminobutyric acid shunt in the tricarbonic acid cycle, while ethanol fermentation compensated the reduced ATP production after inhibition of the oxidative phosphorylation. PMID:23660836

  1. Inhibition of fibroblast growth factor 19 reduces tumor growth by modulating beta-catenin signaling.

    PubMed

    Pai, Rama; Dunlap, Debra; Qing, Jing; Mohtashemi, Iman; Hotzel, Kathy; French, Dorothy M

    2008-07-01

    Fibroblast growth factors (FGF) play important roles in development, angiogenesis, and cancer. FGF19 uniquely binds to FGF receptor 4 (FGFR4). Our previous study has shown that FGF19 transgenic tumors have an activated Wnt-pathway phenotype. Wnt signaling is implicated in initiating or promoting FGF signaling in various cell types and organs. In this study, we examined whether FGF19 or inhibition of FGF19 affects the beta-catenin signaling pathway using human colon cancer cell lines (HCT116, Colo201). Our results show that FGF19 increases tyrosine phosphorylation of beta-catenin and causes loss of beta-catenin-E-cadherin binding. FGF19 increases p-GSK3beta and active beta-catenin levels and anti-FGF19 antibody (1A6) treatment abrogates this effect of FGF19. Anti-FGF19 antibody treatment increases S33/S37/T41 phosphorylation and ubiquitination of beta-catenin. Ion-trap mass spectrometric analysis confirmed that 1A6 increases phosphorylation of beta-catenin in the NH(2) terminus. Using HCT116-paired beta-catenin knockout cells, we show that FGF19 induces TCF/LEF reporter activity in parental (WT/Delta45) and in WT/--but not in mutant (-/Delta45) cells, and that inhibition of endogenous FGF19 reduces this reporter activity, indicating that wild-type beta-catenin is accessible for modulation. FGFR4 knockdown using inducible short hairpin RNA significantly reduces the colony-forming ability in vitro and tumor growth in vivo. Although cleaved caspase-3 immunoreactivity remains unchanged, the number of ki67-positive nuclei is reduced in FGFR4 knockdown tumor xenograft tissues. Consistent with the reduced beta-catenin activation, Taqman analyses show that FGF19/FGFR4 inhibition reduced beta-catenin target gene (cyclin D1, CD44, c-jun, Cox-2, UPAR) expression. These findings highlight that FGF19/FGFR4 cross-talk with beta-catenin and that pathway intervention reduces tumor growth. PMID:18593907

  2. Influence of some growth regulators and cations on inhibition of chlorophyll biosynthesis by lead in maize

    SciTech Connect

    Sinha, S.K. (Council of Science Technology, Lucknow (India)); Srivastava, H.S. (Rohilkhand Univ., Bareilly (India)); Tripathi, R.D. (National Botanical Research Institute, Lucknow (India))

    1993-08-01

    Phytotoxic effects of Pb pollution are well established. In order to analyse the physiological basis of toxic symptoms and of reduced plant productivity, its effect on chlorophyll content has been examined in some plants. Thus, a decrease in total chlorophyll content during Pb supply has been observed in oats, mung beam, pea, etc. The activity of delta aminolevulinic acid dehydratase, an important enzyme in the biosynthesis of heme pigments, is inhibited by Pb in mung bean and several other species. This observation may perhaps indicate that a reduction in chlorophyll content in the presence of lead is due to an inhibition of pigment synthesis. The effect of Pb on greening maize leaf segments in the presence of various precursors of chlorophyll has been studied in the present investigation to evaluate this hypothesis. The effect of some growth regulators and cations, which could otherwise modify chlorophyll biosynthesis, has been examined to see whether the toxic effects of Pb on photosynthetic pigments could also be modified by these effectors. 16 refs., 4 tabs.

  3. Amino Acids (2002) 22: 297308 Peptoid inhibition of trypanothione reductase as a potential

    E-print Network

    Schnaufer, Achim

    2002-01-01

    Amino Acids (2002) 22: 297­308 Peptoid inhibition of trypanothione reductase as a potential of the parasite- specific enzyme trypanothione reductase. A lead inhibitor based on a peptoid structure was designed in the present study based on the known strong competitive inhibition of trypanothione reductase

  4. Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts

    SciTech Connect

    Sandler, Charlotta [Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Helsinki (Finland); Joutsiniemi, Saima [Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Helsinki (Finland); Lindstedt, Ken A. [Wihuri Research Institute, Helsinki (Finland); Juutilainen, Timo [Department of Orthopedic Surgery, Helsinki University Central Hospital, Helsinki (Finland); Kovanen, Petri T. [Wihuri Research Institute, Helsinki (Finland); Eklund, Kari K. [Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Helsinki (Finland)]. E-mail: kari.eklund@hus.fi

    2006-08-18

    Synovial fibroblast is the key cell type in the growth of the pathological synovial tissue in arthritis. Here, we show that platelet-derived growth factor (PDGF) is a potent mitogen for synovial fibroblasts isolated from patients with rheumatoid arthritis. Inhibition of PDGF-receptor signalling by imatinib mesylate (1 {mu}M) completely abrogated the PDGF-stimulated proliferation and inhibited approximately 70% of serum-stimulated proliferation of synovial fibroblasts. Similar extent of inhibition was observed when PDGF was neutralized with anti-PDGF antibodies, suggesting that imatinib mesylate does not inhibit pathways other than those mediated by PDGF-receptors. No signs of apoptosis were detected in synovial fibroblasts cultured in the presence of imatinib. These results suggest that imatinib mesylate specifically inhibits PDGF-stimulated proliferation of synovial fibroblasts, and that inhibition of PDGF-receptors could represent a feasible target for novel antirheumatic therapies.

  5. Inhibition of ethylene production in sunflower cell suspensions by the plant growth retardant BAS 111..W: Possible relations to changes in polyamine and cytokinin contents

    Microsoft Academic Search

    K. Grossmann; F. Siefert; J. Kwiatkowski; M. Schraudner; C. Langebartels; H. Sandermann

    1993-01-01

    At a concentration of 10?5 mol · L?1 the triazole-type growth retardant BAS 111..W completely inhibited the transiently elevated ethylene production in the exponential\\u000a growth phase of heterotrophic sunflower cell suspensions. This effect, which could not be restored by adding gibberellin A3, was accompanied by transiently increased levels of 1-aminocyclopropanecarboxylic acid (ACC) in the cells, which was increasingly\\u000a converted to

  6. Inhibition of prostate cancer growth by muscadine grapeskin extract and resveratrol through distinct mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytochemicals are naturally occurring compounds with demonstrated anti-tumor activities. The phytochemical resveratrol, contained in red grapes, has been shown to inhibit prostate cancer cell growth, potentially through its anti-oxidant activity. Muscadine grapes contain different phytochemical con...

  7. Bacterial growth inhibition produced by root canal sealer cements with a calcium hydroxide base.

    PubMed

    Canalda, C; Pumarola, J

    1989-07-01

    Inhibition of growth of six bacterial strains produced by two root canal sealers with a calcium hydroxide base, CRCS and Sealapex sealers, is studied. The results are compared with those obtained with two zinc oxide eugenol sealers and one epoxy resin. The inhibition produced with the calcium hydroxide sealers is similar to that obtained with the other sealers. The component of paraformaldehyde in a sealer increases the inhibition significantly. PMID:2755695

  8. Boric acid application guidelines for intergranular corrosion inhibition

    Microsoft Academic Search

    Piskor

    1990-01-01

    A significant fraction of the operating Pressurized Water Reactor steam generators have used or are using boric acid as an inhibitor to control stress corrosion cracking, intergranular attack, or denting. Boric acid is applied on line, or by means of crevice flushing, low power soaks, or a combination of these methods. When boric acid is used, it is important to

  9. Corrosion inhibition of steel in concrete by carboxylic acids

    Microsoft Academic Search

    K. K. Sagoe-Crentsil; F. P. Glasser; V. T. Yilmaz

    1993-01-01

    Water soluble carboxylic acids have been used as corrosion inhibitors. They remain largely soluble after curing in cement for up to 90d. Corrosion current measurements are presented showing malonic acid, a dicarboxylic acid, to be a very effective corrosion inhibitor even in the presence of 2.5 wt % chloride. Unfortunately, it has an initial retarding effect on the set of

  10. Investigation of inhibition effect of some amino acids against steel corrosion in HCl solution

    NASA Astrophysics Data System (ADS)

    Ashassi-Sorkhabi, H.; Majidi, M. R.; Seyyedi, K.

    2004-03-01

    The inhibition effect of three amino acids against steel corrosion in HCl solutions has been investigated by potentiodynamic polarization method. Corrosion data such as corrosion rate, corrosion potential ( Ecorr) and corrosion resistance ( Rp) were determined by extrapolation of the cathodic and anodic Tafel region. Adsorption isotherm was investigated by weight-loss measurement. The used amino acids were alanine, glycine and leucine. The effect of inhibitor concentration and acid concentration against inhibitor action was investigated. The inhibition efficiency (IE) depended on the type of amino acid and its concentration. The inhibition effect ranged from 28 to 91%. The amino acids act as a corrosion inhibitor in HCl solution through adsorption on the steel surface and adsorption follows Langmuir isotherm.

  11. Diethylstilbestrol inhibits tumor growth and prolactin production in rat pituitary tumors.

    PubMed Central

    Lloyd, R. V.; Landefeld, T. D.; Maslar, I.; Frohman, L. A.

    1985-01-01

    Treatment of rats bearing transplantable MtT/W15 tumors with 10 mg of diethylstilbestrol (DES) for 3 weeks led to inhibition of tumor growth. The inhibition of tumor growth was reversible after removal of the DES. Histologic examination revealed decreased mitotic activity; however, DES did not produce cell necrosis. Concomitantly, the anterior pituitary glands of animals treated with DES became hyperplastic, with an increased number of prolactin (PRL)-producing cells. DES resulted in a decreased number of PRL cells in the tumor and decreased serum PRL/tumor weight, compared with that of control rats. There was also an increase in the number of growth hormone (GH) tumor cells and an increased serum GH/tumor weight. 17 beta-Estradiol had an effect similar to that of DES, while progesterone did not inhibit tumor growth or cause pituitary cell hyperplasia. Ovariectomy resulted in a decrease in the tumor growth rate, compared with that of control animals, suggesting that the MtT/W 15 tumors are relatively dependent on estrogens for optimal growth. These results indicate that DES inhibition of MtT/W 15 tumor growth is an excellent model for study of the mechanism of the inhibition of tumor growth and the modification of GH and PRL expression by the tumor cells. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3976841

  12. A role for AMPK in the inhibition of glucose-6-phosphate dehydrogenase by polyunsaturated fatty acids

    SciTech Connect

    Kohan, Alison B.; Talukdar, Indrani; Walsh, Callee M. [Department of Biochemistry, West Virginia University, Morgantown, WV (United States)] [Department of Biochemistry, West Virginia University, Morgantown, WV (United States); Salati, Lisa M., E-mail: lsalati@hsc.wvu.edu [Department of Biochemistry, West Virginia University, Morgantown, WV (United States)

    2009-10-09

    Both polyunsaturated fatty acids and AMPK promote energy partitioning away from energy consuming processes, such as fatty acid synthesis, towards energy generating processes, such as {beta}-oxidation. In this report, we demonstrate that arachidonic acid activates AMPK in primary rat hepatocytes, and that this effect is p38 MAPK-dependent. Activation of AMPK mimics the inhibition by arachidonic acid of the insulin-mediated induction of G6PD. Similar to intracellular signaling by arachidonic acid, AMPK decreases insulin signal transduction, increasing Ser{sup 307} phosphorylation of IRS-1 and a subsequent decrease in AKT phosphorylation. Overexpression of dominant-negative AMPK abolishes the effect of arachidonic acid on G6PD expression. These data suggest a role for AMPK in the inhibition of G6PD by polyunsaturated fatty acids.

  13. Method of inhibiting crosslinking of aqueous xanthan gums in the presence of ferric acid ions

    SciTech Connect

    Crowe, C.W.

    1982-03-02

    The cross linking of aqueous xanthan gums in the presence of ferric ions is inhibited or prevented by adding a soluble alkanoic and/or alkenoic acid having at least 4 carbon atoms and bearing at least 2 hydroxyl groups per molecule, and/or a soluble salt of ..gamma..-lactone. This combination of ingredients forms gelled acid compositions which are useful in acidizing treatments of wells. The gelled acid compositions are viscous fluids which have increased stability against shear and thermal degradation and other properties which result in retarded reaction rates and reduced fluid leak-off during acidizing treatments of subterranean formations surrounding well bores. The aqueous gelled acids have the further advantage of inhibiting or preventing the formation of insoluble compounds, such as ferric hydroxide, during such acidizing treatments. 13 claims.

  14. Sclareol modulates the Treg intra-tumoral infiltrated cell and inhibits tumor growth in vivo

    Microsoft Academic Search

    Shokoofe Noori; Zuhair M. Hassan; Mehdi Mohammadi; Zohre Habibi; Nooshin Sohrabi; Saeed Bayanolhagh

    2010-01-01

    A regulatory or suppressor T cell is functionally defined as a T cell that inhibits an immune response by influencing the activity of another cell type. On the other hand, Th1 cells express IFN-? and mediate cellular immunity.Sclareol exhibits growth inhibition and cytotoxic activity against a variety of human cancer cell lines. In the first set of experiments, Sclareol was

  15. Abstract. Doxycycline (Dc) has been demonstrated to inhibit cell growth and induce apoptosis in tumor cells,

    E-print Network

    Tian, Weidong

    Abstract. Doxycycline (Dc) has been demonstrated to inhibit cell growth and induce apoptosis of apoptosis, whereas the role of the caspase-9 was limited. Keywords. Doxycycline, apoptosis, mitochondria by inhibiting bacterial protein syn- thesis. Doxycycline (Dc) is a semi-synthetic tetracycline made by modifying

  16. Modeling Growth of Cellulomonas cellulans NRRL B 4567 under Substrate Inhibition During Cellulase Production

    Microsoft Academic Search

    R. Agarwal; B. Mahanty; V. Venkata

    Cellulase production study was performed in shake flask and bioreactor system using Cellulomonas cellulans NRRL B 4567 for initial substrate concentration from S0 = 2 to 12 g L -1. The growth, substrate uptake profile and enzyme activity at different initial substrate concentrations were measured. The results inferred the presence of sub- strate inhibition kinetics. Various substrate inhibition models were

  17. N-acetylcysteine inhibits germination of conidia and growth of Aspergillus spp. and Fusarium spp.

    PubMed Central

    De Lucca, A J; Walsh, T J; Daigle, D J

    1996-01-01

    N-Acetylcysteine inhibited hyphal growth and germination of conidia of Aspergillus spp. and Fusarium spp. N-Acetylcysteine inhibited conidial germination as well as or better than L-cysteine. Cysteine-related compounds may provide a potential therapeutic strategy against agriculturally and medically important fungal pathogens. PMID:8723482

  18. Growth inhibition of bacterial isolates recovered from two types of Portuguese dry smoked sausages ( chouriço)

    Microsoft Academic Search

    T. J. S. Matos; A. Bruno-Soares; B. B. Jensen; A. S. Barreto; O. Hojberg

    2008-01-01

    Potassium sorbate (PS), sodium benzoate (SB) and methyl p-hydroxybenzoate (MHB) were investigated as surface treatments for their ability to inhibit the growth of 18 isolates of spoilage and pathogenic bacteria from two types of Portuguese dry smoked sausages (Chouriço). MHB significantly inhibited the growth rate of 12 of the isolates (p<0.05) whereas no effect was observed for four isolates of

  19. Growth inhibition by exogenous proline and its metabolism in saltgrass ( Distichlis spicata ) suspension cultures

    Microsoft Academic Search

    Manuel M. Rodriguez; James W. Heyser

    1988-01-01

    The growth of Distichlis spicata suspension cultures in LS medium without NaCl was inhibited 54% by 2 mM proline. In medium containing 260 mM NaCl, 10 mM proline inhibited growth by only 22%. The uptake and metabolism of 10 mM L-[1-13C] proline was followed by 13C NMR and ninhydrin analyses of suspensions cultured in the presence of 0 or 260

  20. Microcystin uptake inhibits growth and protein phosphatase activity in mustard ( Sinapis alba L.) seedlings

    Microsoft Academic Search

    Katriina Kurki-Helasmo; Jussi Meriluoto

    1998-01-01

    Mustard (Sinapis alba L.) seeds were cultivated for seven days on a solid nutrient medium supplemented with 0–40?g microcystin-RR per ml. Microcystin-RR affected seedling growth (ic50 0.8?g\\/ml) and microcystin concentrations ?5.0?g\\/ml produced malformed plants. The inhibition of protein phosphatase 1 and 2A activity correlated with the growth inhibition. The seedlings were also shown to take up 3H-dihydromicrocystin-LR derived radioactivity up

  1. Farnesol-induced growth inhibition in Saccharomyces cerevisiae by a cell cycle mechanism

    Microsoft Academic Search

    Kiyotaka Machida; Toshio Tanaka; Yoshihisa Yano; Shuzo Otani; Makoto Taniguchi

    1999-01-01

    The growth of budding yeast, Saccharomyces cerevisiae, was inhibited in medium containing 25 pM farnesol (FOH). The FOH-treated cells were still viable, and were characterized by a transition from budded to unbudded phase as well as a significant loss of intracellular diacylglycerol (DAG). FOH-induced growth inhibition could be effectively prevented by the coaddition of a membrane-permeable DAG analogue which can

  2. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol

    Microsoft Academic Search

    Yvette D. Burke; M. Jennifer Stark; Steven L. Roach; Stephanie E. Sen; Pamela L. Crowell

    1997-01-01

    Fruits and vegetables have protective effects against many human cancers, including pancreatic cancer. Isoprenoids are one\\u000a class of phytochemicals which have antitumor activity, but little is known about their effects on cancer of the pancreas.\\u000a We tested the hypothesis that isoprenoids would inhibit the growth of pancreatic tumor cells. Significant (60–90%) inhibition\\u000a of the anchorage-independent growth of human MIA PaCa2

  3. Somatostatin Analogues Inhibit Growth of Pancreatic Cancer by Stimulating Tyrosine Phosphatase

    Microsoft Academic Search

    C. Liebow; C. Reilly; M. Serrano; A. V. Schally

    1989-01-01

    Several analogues of somatostatin were examined in the Mia PaCa-2 human pancreatic cancer cell line for their ability to promote tyrosine phosphatase activity affecting the receptors for the epidermal growth factor. The inhibition of growth of the Mia PaCa-2 cells in culture was also evaluated to determine the mechanism of action of somatostatin analogues and their relative effectiveness in inhibiting

  4. The FGF-2-Derived Peptide FREG Inhibits Melanoma Growth In Vitro and In Vivo

    PubMed Central

    Aguzzi, Maria S; Faraone, Debora; D'Arcangelo, Daniela; De Marchis, Francesco; Toietta, Gabriele; Ribatti, Domenico; Parazzoli, Alberto; Colombo, Paolo; Capogrossi, Maurizio C; Facchiano, Antonio

    2011-01-01

    Previous data report that fibroblast growth factor-2 (FGF-2)-derived peptide FREG potently inhibits FGF-2-dependent angiogenesis in vitro and in vivo. Here, we show that FREG inhibits up to 70% in vitro growth and invasion/migration of smooth muscle and melanoma cells. Such inhibition is mediated by platelet-derived growth factor-receptor-? (PDGF-R?); in fact, proliferation and migration were restored upon PDGF-R? neutralization. Further experiments demonstrated that FREG interacts with PDGF-R? both in vitro and in vivo and stimulates its phosphorylation. We have previously shown that overexpressing PDGF-R? strongly inhibits melanoma growth in vivo; we, therefore, hypothesized that PDGF-R? agonists may represent a novel tool to inhibit melanoma growth in vivo. To support this hypothesis, FREG was inoculated intravenously (i.v.) in a mouse melanoma model and markedly inhibited pulmonary metastases formation. Immunohistochemical analyses showed less proliferation, less angiogenesis, and more apoptosis in metastasized lungs upon FREG treatment, as compared to untreated controls. Finally, in preliminary acute toxicity studies, FREG showed no toxicity signs in healthy animals, and neither microscopic nor macroscopic toxicity at the liver, kidney, and lungs level. Altogether, these data indicate that FREG systemic treatment strongly inhibits melanoma metastases development and indicate for the first time that agonists of PDGF-R? may control melanoma both in vitro and in vivo. PMID:20924364

  5. Inhibition of a medium chain acyl-CoA synthetase involved in glycine conjugation by carboxylic acids

    Microsoft Academic Search

    Fumiyo Kasuya; Kazuo Igarashi; Miyoshi Fukui

    1996-01-01

    Molecular characteristics of carboxylic acids were investigated for the ability to inhibit a purified medium chain acyl-CoA synthetase, using hexanoic acid as a substrate. Salicylic acid, 4-methylsalicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxyoctanoic acid, which do not act as substrates for the medium chain acyl-CoA synthetase, were potent as inhibitors. Valproic acid was not an inhibitor. Salicylic acid, 2-hydroxynaphthoic acid, and

  6. Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation

    PubMed Central

    Ionta, M.; Rosa, M.C.; Almeida, R.B.; Freitas, V.M.; Rezende-Teixeira, P.; Machado-Santelli, G.M.

    2012-01-01

    Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1?µM) and cAMP (1?mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3?) and liver differentiation [E-cadherin, connexin 26 (Cx26), and connexin 32 (Cx32)]. RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3? (inactive form) expression while the expression of Cx43, Tyr216-GSK-3? (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells. PMID:22618858

  7. Pharmacologic retinoid signaling and physiologic retinoic acid receptor signaling inhibit basal cell carcinoma tumorigenesis

    PubMed Central

    So, Po-Lin; Fujimoto, Michele A.; Epstein, Ervin H.

    2015-01-01

    Basal cell carcinoma (BCC) is the most common human cancer. Patients with basal cell nevus syndrome (Gorlin syndrome) are highly susceptible to developing many BCCs as a result of a constitutive inactivating mutation in one allele of PATCHED 1, which encodes a tumor suppressor that is a major inhibitor of Hedgehog signaling. Dysregulated Hedgehog signaling is a common feature of both hereditary and sporadic BCCs. Recently, we showed remarkable anti-BCC chemopreventive efficacy of tazarotene, a retinoid with retinoic acid receptor (RAR) ?/? specificity, in Ptch1 +/? mice when treatment was commenced before carcinogenic insults. In this study, we assessed whether the effect of tazarotene against BCC carcinogenesis is sustained after its withdrawal and whether tazarotene is effective against preexisting microscopic BCC lesions. We found that BCCs did not reappear for at least 5 months after topical drug treatment was stopped and that already developed, microscopic BCCs were susceptible to tazarotene inhibition. In vitro, tazarotene inhibited a murine BCC keratinocyte cell line, ASZ001, suggesting that its effect in vivo is by direct action on the actual tumor cells. Down-regulation of Gli1, a target gene of Hedgehog signaling and up-regulation of CRABPII, a target gene of retinoid signaling, were observed with tazarotene treatment. Finally, we investigated the effects of topical applications of other retinoid-related compounds on BCC tumorigenesis in vivo. Tazarotene was the most effective of the preparations studied, and its effect most likely was mediated by RAR? activation. Furthermore, inhibition of basal RAR signaling in the skin promoted BCC carcinogenesis, suggesting that endogenous RAR signaling restrains BCC growth. PMID:18483315

  8. Efficient inhibition of intraperitoneal human ovarian cancer growth by short hairpin RNA targeting CD44.

    PubMed

    Zou, L; Yi, T; Song, X; Li, S; Wei, Y; Zhao, X

    2014-01-01

    CD44 is one member of a big glycoprotein family involved in adhesion of cells or cells and extracellular matrix (ECM). The heavily glycosylated CD44 has been proved to be a major receptor of hyaluronan and a marker of stem cells in ovarian cancer. Here, using short hairpin (shRNA) against CD44, we demonstrate that knockdown CD44 could inhibit cancer growth efficiently compared with controls. Plasmid targeting CD44 gene (pshCD44) or non-relative control sequences (pshHK) was constructed and delivered to ovarian cancer by biodegradable poly D, L-Lactide-co-glycolide acid nanoparticles (PLGANPs). Nude mice were utilized in an intraperitoneal model of ovarian carcinomatosis to assess antitumor efficacy in vivo. Antitumor efficacy was estimated by changes in tumor weights, proliferation (Ki-67), apoptosis (TUNEL) and angiogenesis (CD31 staining and alginate-encapsulated tumor beads assay) in tumor cells. As results, pshCD44 or pshHK could be effectively transfected into SKOV-3 cells by PLGANPs. Tumor weight in pshCD44/PLGANPs group was suppressed by 45% and 50% compared with those in pshHK/PLGANPs and untreated group, respectively (Ps < 0.001). Inhibition of cell proliferation, induction of apoptosis and reduction of angiogenesis in tumor cells of pshCD44/PLGANPs group also show significant difference compared with those in control groups (Ps < 0.05), respectively. These results indicate that pshCD44 delivered by PLGANPs might be a potential approach in ovarian cancer therapy, and point towards a mechanism involving the inhibition of angiogenesis, cellular proliferation and the induction of apoptosis. PMID:24824928

  9. miR-29b represses intestinal mucosal growth by inhibiting translation of cyclin-dependent kinase 2

    PubMed Central

    Xiao, Lan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Cao, Shan; Martindale, Jennifer L.; Su, Weijie; Chung, Hee Kyoung; Gorospe, Myriam; Wang, Jian-Ying

    2013-01-01

    The epithelium of the intestinal mucosa is a rapidly self-renewing tissue in the body, and defects in the renewal process occur commonly in various disorders. microRNAs (miRNAs) posttranscriptionally regulate gene expression and are implicated in many aspects of cellular physiology. Here we investigate the role of miRNA-29b (miR-29b) in the regulation of normal intestinal mucosal growth and further validate its target mRNAs. miRNA expression profiling studies reveal that growth inhibition of the small intestinal mucosa is associated with increased expression of numerous miRNAs, including miR-29b. The simple systemic delivery of locked nucleic acid–modified, anti–miR-29b-reduced endogenous miR-29b levels in the small intestinal mucosa increases cyclin-dependent kinase 2 (CDK2) expression and stimulates mucosal growth. In contrast, overexpression of the miR-29b precursor in intestinal epithelial cells represses CDK2 expression and results in growth arrest in G1 phase. miR-29b represses CDK2 translation through direct interaction with the cdk2 mRNA via its 3?-untranslated region (3?-UTR), whereas point mutation of miR-29b binding site in the cdk2 3?-UTR prevents miR-29b–induced repression of CDK2 translation. These results indicate that miR-29b inhibits intestinal mucosal growth by repressing CDK2 translation. PMID:23904268

  10. Phenotype dependence in the inhibition of red cell acid phosphatase (ACP) by folates.

    PubMed

    Sensabaugh, G F; Golden, V L

    1978-09-01

    Red cell acid phosphatase (ACP) is shown to be inhibited by folic acid and various folates. The degree of inhibition is phenotype dependent with a pattern of variation differing from that of the well recognized variation in red cell activity levels. The pattern of variation is ordered ACP1B less than ACP1A less than ACP1C in terms of the relative allelic contributions to the observed inhibition. This pattern correlates with previously observed patterns of risk for two hemolytic disorders and may thus provide a key to their understanding. PMID:736044

  11. Immunostimulatory DNA Inhibits Transforming Growth Factor Expression and Airway Remodeling

    Microsoft Academic Search

    Jae Youn Cho; Marina Miller; Kwang Je Baek; Ji Won Han; Jyothi Nayar; Monica Rodriguez; Sook Young Lee; Kirsti McElwain; Shauna McElwain; Eyal Raz; David H. Broide

    Immunostimulatory sequences of DNA (ISS) inhibit eosinophilic air- way inflammation, Th2 responses, and airway hyperreactivity (AHR) in mouse models of acute ovalbumin (OVA)-induced airway inflam- mation. To determine whether ISS inhibits airway remodeling, we developed a mouse model of airway remodeling in which OVA- sensitized mice were repeatedly exposed to intranasal OVA adminis- tration for 1-6 mo. Mice chronically exposed

  12. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles.

    PubMed

    Hannon, Patrick R; Brannick, Katherine E; Wang, Wei; Gupta, Rupesh K; Flaws, Jodi A

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1-100 ?g/ml) for 24-96 h to establish the temporal effects of DEHP on the follicle. Following 24-96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17?-hydroxylase-17,20-desmolase, 17?-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. PMID:25701202

  13. 2,3-Dihydroxybenzoic Acid-Containing Nanofiber Wound Dressings Inhibit Biofilm Formation by Pseudomonas aeruginosa

    PubMed Central

    Ahire, Jayesh J.

    2014-01-01

    Pseudomonas aeruginosa forms biofilms in wounds, which often leads to chronic infections that are difficult to treat with antibiotics. Free iron enhances biofilm formation, delays wound healing, and may even be responsible for persistent inflammation, increased connective tissue destruction, and lipid peroxidation. Exposure of P. aeruginosa Xen 5 to the iron chelator 2,3-dihydroxybenzoic acid (DHBA), electrospun into a nanofiber blend of poly(d,l-lactide) (PDLLA) and poly(ethylene oxide) (PEO), referred to as DF, for 8 h decreased biofilm formation by approximately 75%. This was shown by a drastic decline in cell numbers, from 7.1 log10 CFU/ml to 4.8 log10 CFU/ml when biofilms were exposed to DF in the presence of 2.0 mM FeCl3 6H2O. A similar decline in cell numbers was recorded in the presence of 3.0 mM FeCl3 6H2O and DF. The cells were more mobile in the presence of DHBA, supporting the observation of less biofilm formation at lower iron concentrations. DHBA at MIC levels (1.5 mg/ml) inhibited the growth of strain Xen 5 for at least 24 h. Our findings indicate that DHBA electrospun into nanofibers inhibits cell growth for at least 4 h, which is equivalent to the time required for all DHBA to diffuse from DF. This is the first indication that DF can be developed into a wound dressing to treat topical infections caused by P. aeruginosa. PMID:24449781

  14. Inhibition of constitutive Akt (PKB) phosphorylation by docosahexaenoic acid in the human breast cancer cell line MDA-MB-453.

    PubMed

    Sato, Satoshi B; Park, Jungha; Kawamoto, Jun; Sato, Sho; Kurihara, Tatsuo

    2013-02-01

    Many breast cancer cells express aberrantly activated receptor tyrosine kinases and are associated with deregulated phosphorylation of Akt (PKB). They are also often associated with a high level of free monounsaturated (MUFA) and saturated (SFA) fatty acids. We studied the effect of DHA and other polyunsaturated fatty acids (PUFAs) on these anomalies in a human breast cancer cell line, MDA-MB-453. Inhibitors of the Akt T308 kinase (PDK1) or S473 kinase (mTORC2, DNA-dependent protein kinase and integrin-linked kinase) and combinations of two of them incompletely inhibited, or even enhanced, the phosphorylation in this cell line. In contrast, it was found that DHA as well as other PUFAs inhibited Akt phosphorylation on T308 after 24h. These PUFAs also blocked phosphorylation of S473, although certain omega-6 PUFAs were ineffective. After 48h, only DHA inhibited Akt phosphorylation on the both residues. DHA, and other PUFAs though less efficiently, also elevated the expression of a mitochondrial enzyme, 2,4-dienoyl-CoA reductase, which catalyzes process necessary for ?-oxidation of PUFAs. These PUFAs were present in the cells at high concentrations and reduced the amount of free and phospholipid-bound MUFAs. DHA most efficiently blocked deregulated cell proliferation while the effects of other PUFAs were moderate. These results suggest that DHA suppressed the growth of the cancer cell through its specifically persistent block of Akt phosphorylation in conjunction with modulation of fatty acid metabolism. PMID:23085420

  15. Inhibition of hydroxycinnamic acid sulfation by flavonoids and their conjugated metabolites.

    PubMed

    Wong, Chi Chun; Williamson, Gary

    2013-01-01

    Hydroxycinnamic acids and flavonoids are dietary phenolic antioxidants that are abundant in our diet. Hydroxycinnamic acids are highly sulfated in vivo, and sulfotransferases (SULTs), in particular SULT1A1, play a major role in their metabolism. Flavonoids are potent inhibitors of human SULTs. In this study, the potential metabolic interaction between dietary hydroxycinnamic acids and flavonoids was investigated. Flavonoids, such as luteolin, quercetin, daidzein, and genistein, are identified as potent inhibitors of hydroxycinnamic acid sulfation in human liver S9 homogenate with IC50 values <1 µM. The inhibitory activity was less potent in the human intestinal S9 homogenate. We also demonstrate that quercetin conjugates found in vivo (quercetin-3-O-glucuronide, quercetin-7-O-glucuronide, and quercetin-3'-O-sulfate) moderately inhibited the sulfation of hydroxycinnamic acids in human liver S9. In an intact cellular system, human HepG2 cells, caffeic acid and ferulic acid sulfation was inhibited by luteolin and quercetin (IC50 : 1.6-3.9 µM). Quercetin-3'-O-sulfate weakly inhibited sulfation. Quercetin glucuronides, limited by their low cellular uptake, were ineffective. These data suggest that the inhibition of SULTs by flavonoids and in vivo flavonoid conjugates may modify the bioavailability of dietary hydroxycinnamic acids by suppressing their conversion to sulfated metabolites. PMID:24038617

  16. Investigation of inhibition effect of some amino acids against steel corrosion in HCl solution

    Microsoft Academic Search

    H. Ashassi-Sorkhabi; M. R Majidi; K. Seyyedi

    2004-01-01

    The inhibition effect of three amino acids against steel corrosion in HCl solutions has been investigated by potentiodynamic polarization method. Corrosion data such as corrosion rate, corrosion potential (Ecorr) and corrosion resistance (Rp) were determined by extrapolation of the cathodic and anodic Tafel region. Adsorption isotherm was investigated by weight-loss measurement. The used amino acids were alanine, glycine and leucine.

  17. Environmentally safe corrosion inhibition of the Cu–Ni alloys in acidic sulfate solutions

    Microsoft Academic Search

    Waheed A. Badawy; Khaled M. Ismail; Ahlam M. Fathi

    2005-01-01

    The corrosion and passivation behaviors of alloys with different Cu–Ni ratios were investigated in acidic sulfate solutions. The corrosion rate was calculated and the corrosion inhibition process was investigated using different amino acids as corrosion inhibitors. For these investigations conventional electrochemical techniques and electrochemical impedance spectroscopy (EIS) were used. Fitting of the experimental impedance data to theoretical values enables understanding

  18. Inhibition of growth and swarming of Proteus mirabilis and Proteus vulgaris by triclosan.

    PubMed Central

    Firehammer, B D

    1987-01-01

    The MICs of triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) and the effect on swarming were determined for 35 isolates of Proteus mirabilis and 7 isolates of P. vulgaris of animal origin. Both species were susceptible to the antimicrobial agent, and growth of all but one isolate was inhibited by less than 1 microgram/ml in broth and on agar without blood. Swarming was inhibited at triclosan concentrations two- to fourfold less than the MICs. Higher concentrations were required with blood agar than with plain agar for inhibition of growth and swarming. PMID:3301894

  19. Amino Acid Substitutions in the Pore Helix of GluR6 Control Inhibition by Membrane Fatty Acids

    PubMed Central

    Wilding, Timothy J.; Fulling, Elisabeth; Zhou, Yun; Huettner, James E.

    2008-01-01

    RNA editing at the Q/R site in the GluR5 and GluR6 subunits of neuronal kainate receptors regulates channel inhibition by lipid-derived modulators including the cis-unsaturated fatty acids arachidonic acid and docosahexaenoic acid. Kainate receptor channels in which all of the subunits are in the edited (R) form exhibit strong inhibition by these compounds, whereas wild-type receptors that include a glutamine (Q) at the Q/R site in one or more subunits are resistant to inhibition. In the present study, we have performed an arginine scan of residues in the pore loop of the GluR6(Q) subunit. Amino acids within the range from ?19 to +7 of the Q/R site of GluR6(Q) were individually mutated to arginine and the mutant cDNAs were expressed as homomeric channels in HEK 293 cells. All but one of the single arginine substitution mutants yielded functional channels. Only weak inhibition, typical of wild-type GluR6(Q) channels, was observed for substitutions +1 to +6 downstream of the Q/R site. However, arginine substitution at several locations upstream of the Q/R site resulted in homomeric channels exhibiting strong inhibition by fatty acids, which is characteristic of homomeric GluR6(R) channels. Based on homology with the pore loop of potassium channels, locations at which R substitution induces susceptibility to fatty acid inhibition face away from the cytoplasm toward the M1 and M3 helices and surrounding lipids. PMID:18562501

  20. Effects of the fermentation product of herbs by lactic acid bacteria against phytopathogenic filamentous fungi and on the growth of host plants

    Microsoft Academic Search

    Shinsuke Kuwaki; Iichiro Ohhira; Masumi Takahata; Atsuko Hirota; Yoshiyuki Murata; Mikiro Tada

    2004-01-01

    The fermentation product of herbs by lactic acid bacteria (FHL) was assayed for antifungal activities against Rosellinia necatrix, Helicobasidium mompa, Fusarium oxysporum, Pythium graminicola and Pyricularia oryzae. FHL completely inhibited the growth of R. necatrix, H. mompa, P. graminicola and P. oryzae, and reduced the growth of F. oxysporum by 35%. When the seeds of Medicago sativa L. (alfalfa), Asparagus

  1. Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type1) diabetic rats

    PubMed Central

    Nagai, Ryoji; Nagai, Mime; Shimasaki, Satoko; Baynes, John W.; Fujiwara, Yukio

    2010-01-01

    Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end products (AGEs) such as N?-(carboxyethyl)lysine (CEL) and N?-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis . We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes. PMID:20117096

  2. Mechanism of inhibition caused by long-chain fatty acids in anaerobic digestion process

    SciTech Connect

    Hanaki, K.; Matsuo, T.; Nagase, M.

    1981-07-01

    The inhibitory effect of long-chain fatty acids on the anaerobic digestion process was examined in batch experiments using synthetic substrates. The addition of long-chain fatty acids caused the appearance of the lag period in the methane production from acetate and in the degradation of both long-chain fatty acids and n-butyrate. Methane production from hydrogen proceeded without lag period although its rate was lowered. Fermentation of glucose was not inhibited. Neutral fat in the whole milk was easily hydrolyzed to long-chain fatty acids, which brought about the inhibtion. The addition of calcium chloride reduced the inhibitory effect of long-chain fatty acids, but it did not do so after the culture had been exposed to long-chain fatty acids for more than several hours. The addition of calcium carbonate could not reduce the inhibition because of its insolubility. 18 refs.

  3. Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway.

    PubMed

    Wu, Min; Harvey, Kevin A; Ruzmetov, Nargiz; Welch, Zachary R; Sech, Laura; Jackson, Kim; Stillwell, William; Zaloga, Gary P; Siddiqui, Rafat A

    2005-11-10

    The effect of fish oils and their active omega-3 fatty acid constituents, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were investigated on breast cancer growth. In in vivo experiments, mice were fed diets that were rich in either omega-3 (fish oil) or omega-6 (corn oil) fatty acids. Three weeks after implantation of MDA-MB-231 breast cancer cells, the tumor volume and weight were significantly lower (p < 0.05) for mice fed the omega-3 diets compared to those fed the omega-6 diets. Dietary fish oil also caused a 40% (p < 0.05) increase in neutral sphingomyelinase (N-SMYase) activity in the tumors. The tumor tissues from fish oil-fed animals expressed elevated p21 (waf1/cip1) mRNA, whereas tumor tissues from corn oil-fed animals exhibited undetectable levels of p21 expression. In in vitro experiments, at concentrations as low as 25 muM, DHA and EPA inhibited the growth of cultured MDA-MB-231 cells in a dose-dependent manner by 20-25% (p < 0.05). N-SMYase activity was also increased by 30-40% (p < 0.05) in the DHA- or EPA-treated cells in which an increase in ceramide formation was observed. DHA and EPA were both observed to enhance membrane bleb formation and also to induce the expression of p21. Omega-3 fatty acids-induced bleb formation and p21 expression were inhibited by the N-SMYase inhibitor GW4869, which also inhibited apoptosis by approximately 40% (p < 0.05). The results suggest that inhibition of breast cancer growth in nude mice by dietary fish oil and inhibition of breast cancer cell growth in culture by treatment with DHA and EPA is mediated by activation of N-SMYase. PMID:15900589

  4. Ganoderma lucidum extracts inhibit growth and induce actin polymerization in bladder cancer cells in vitro.

    PubMed

    Lu, Qing-Yi; Jin, Yu-Sheng; Zhang, Qifeng; Zhang, Zuofeng; Heber, David; Go, Vay Liang W; Li, Frederick P; Rao, Jian Yu

    2004-12-01

    This study was conducted to investigate chemopreventive effects of Ganoderma lucidum using a unique in vitro human urothelial cell (HUC) model consisted of HUC-PC cells and MTC-11 cells. Ethanol and water extracts of fruiting bodies and spores of the G. lucidum were used to examine growth inhibition, actin polymerization status, and impact of actin remodeling on cell migration and adhesion. Results showed that ethanol extracts had a stronger growth inhibition effect than water extracts. Cell cycle analysis showed that the growth inhibition effect was associated with G2/M arrest. At non-cytotoxic concentrations (40-80 microg/ml), these extracts induced actin polymerization, which in turn inhibited carcinogen 4-aminobiphenyl induced migration in both cell lines. The increased actin polymerization was associated with increased stress fibers and focal adhesion complex formation, however, expression of matrix metalloproteinase-2 and focal adhesion kinase (total and phospholated) were unchanged, which suggests that other mechanisms may be involved. PMID:15500944

  5. Inhibition of Wilms' tumor growth by intramuscular administration of tissue inhibitor of metalloproteinases-4 plasmid DNA.

    PubMed

    Celiker, M Y; Wang, M; Atsidaftos, E; Liu, X; Liu, Y E; Jiang, Y; Valderrama, E; Goldberg, I D; Shi, Y E

    2001-07-19

    Extracellular matrix (ECM) degrading matrix metalloproteinases (MMPs) lead to ECM turnover, a key event in cancer growth and progression. The tissue inhibitors of matrix metalloproteinases (TIMPs) limit the activity of MMPs, which suggests their use for cancer gene therapy. Here we report that systemic administration of naked TIMP-4 DNA significantly inhibited Wilms' tumor growth in nude mice. TIMP-4, whose expression was lost in Wilms' tumor, inhibited the growth of G401 Wilms' tumor cells at a concentration lower than those required for MMP inhibition. This inhibition was associated with internalization of exogenous recombinant TIMP-4. Electroporation-mediated intramuscular injection of TIMP-4 expression plasmid resulted in sustained plasma TIMP-4 levels and significant tumor suppression. Our data demonstrate a tumor suppressive effect of TIMP-4 against Wilms' tumor and the potential utility of intramuscular delivery of TIMP gene for treatment of kidney derived cancers. PMID:11466614

  6. Inhibition of Microbial Growth by Fatty Amine Catalysts from Polyurethane Foam Test Tube Plugs

    PubMed Central

    Bach, John A.; Wnuk, Richard J.; Martin, Delano G.

    1975-01-01

    When polyurethane foam test tube plugs are autoclaved, they release volatile fatty amines that inhibit the growth of some microorganisms. The chemical structures of these amines were determined by the use of a gas chromatographmass spectrometer. They are catalysts used to produce the foam. The problem of contaminating growth media with toxic substances released from polymeric materials is discussed. PMID:1096816

  7. Inhibition of Wilms' tumor growth by intramuscular administration of tissue inhibitor of metalloproteinases-4 plasmid DNA

    Microsoft Academic Search

    M Y Çeliker; M Wang; E Atsidaftos; X Liu; Y E Liu; Y Jiang; E Valderrama; I D Goldberg; Y E Shi

    2001-01-01

    Extracellular matrix (ECM) degrading matrix metalloproteinases (MMPs) lead to ECM turnover, a key event in cancer growth and progression. The tissue inhibitors of matrix metalloproteinases (TIMPs) limit the activity of MMPs, which suggests their use for cancer gene therapy. Here we report that systemic administration of naked TIMP-4 DNA significantly inhibited Wilms' tumor growth in nude mice. TIMP-4, whose expression

  8. Boric acid application guidelines for intergranular corrosion inhibition

    SciTech Connect

    Piskor, S.R. (Westinghouse Electric Corp., Pittsburgh, PA (USA). Nuclear Services Div.)

    1990-12-01

    A significant fraction of the operating Pressurized Water Reactor steam generators have used or are using boric acid as an inhibitor to control stress corrosion cracking, intergranular attack, or denting. Boric acid is applied on line, or by means of crevice flushing, low power soaks, or a combination of these methods. When boric acid is used, it is important to have knowledge about its chemical and physical properties, its effect on corrosion, and its correct application. The data on these subjects may be found in a diversity of sources, which are often not readily available or convenient to use. In addition, new information has recently become available. This report has been prepared and revised to be comprehensive treatise on boric acid relevant to its application in nuclear steam generators. Relevant boric acid information from 1987--89 has been added to provide the latest available data from laboratory testing and power plant application. 5 figs.

  9. Corrosion inhibition and adsorption behavior of methionine on mild steel in sulfuric acid and synergistic effect of iodide ion

    Microsoft Academic Search

    E. E. Oguzie; Y. Li; F. H. Wang

    2007-01-01

    The corrosion inhibition of mild steel in sulfuric acid by methionine (MTI) was investigated using electrochemical techniques. The effect of KI additives on corrosion inhibition efficiency was also studied. The results reveal that MTI inhibited the corrosion reaction by adsorption onto the metal\\/solution interface. Inhibition efficiency increased with MTI concentration and synergistically increased in the presence of KI, with an

  10. Effect of dietary acid or aluminum on growth and growth-related hormones in mallard ducklings ( Anas platyrhynchos )

    Microsoft Academic Search

    M. C. Capdevielle; C. G. Scanes

    1995-01-01

    Acid precipitation may exert negative effects on growth and survival of birds whether by the acid itself (H+ ions) or by aluminum consumption due to increased solubility at low pHs. The effects of aluminum or acid on growth-related hormones were compared in mallard ducklings: growth hormone, insulin-like growth factor, and insulin-like growth factor binding proteins (IGFBPs). Birds received two levels

  11. Transplanted tumor growth inhibition by functionalized short single-walled carbon nanotubules.

    PubMed

    Kit, O I; Zlatnik, E Yu; Peredreyeva, L V; Chervonobrodov, S P

    2014-01-01

    The effects of short single-walled carbon nanotubules functionalized by COOH- and NH2- containing groups (NT-COOH and NT-NH2), on the dynamics of transplanted Pliss lymphosarcoma growth were studied after tumor cell preincubation with nanotubules and after injection of nanotubules into the developing tumor. Tumor growth was inhibited and the lifespan of rats with tumors was prolonged by 1.7 times after transplantation of tumor preincubated with NT-NH2, while NT-COOH caused no effect of this kind. Intratumor injection of NT-NH2 inhibited tumor growth over 3 weeks and prolonged animal lifespan. PMID:24771378

  12. Antiandrogenic activity of anthranilic acid ester derivatives as novel lead structures to inhibit prostate cancer cell proliferation.

    PubMed

    Roell, Daniela; Rösler, Thomas W; Degen, Stephanie; Matusch, Rudolf; Baniahmad, Aria

    2011-06-01

    A plant extract from the fruits of saw palmetto, which is currently used to treat the androgen-dependent benign prostatic hyperplasia and PCa, served as source for new structure variants. We investigated the antiandrogenic potential of an ethanolic total extract and one of its main aromatic components anthranilic acid. An androgen receptor-antagonistic (antiandrogenic) effect of the extract was evident, and although anthranilic acid itself revealed no remarkable effect, its methyl ester, methyl anthranilate, exhibited antiandrogenic potential. Based on this chemical structure, we synthesized and investigated the antiandrogenic activity of four AnA ester derivatives, which were either novel or only little described in literature. These AnA esters inhibit the androgen-dependent transactivation of both the wild-type (wt) androgen receptor and the androgen receptor point mutant T877A, which often occurs in refractory PCa. Moreover, they inhibit the androgen receptor-induced expression of the endogenous prostate-specific antigen. Importantly, AnA esters repress the growth of human PCa cells. Deletion analyses of androgen receptor propose that the antiandrogenic effect of anthranilic acid esters is mediated by the ligand-binding domain, most likely through direct binding, without affecting androgen receptor protein levels. Taken together, the data suggest antiandrogenic potential of anthranilic acid ester derivatives, which can serve as lead structures for novel antiandrogens. PMID:21439024

  13. EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells

    PubMed Central

    Jung, Y D; Kim, M S; Shin, B A; Chay, K O; Ahn, B W; Liu, W; Bucana, C D; Gallick, G E; Ellis, L M

    2001-01-01

    Catechins are key components of teas that have antiproliferative properties. We investigated the effects of green tea catechins on intracellular signalling and VEGF induction in vitro in serum-deprived HT29 human colon cancer cells and in vivo on the growth of HT29 cells in nude mice. In the in vitro studies, (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea extract, inhibited Erk-1 and Erk-2 activation in a dose-dependent manner. However, other tea catechins such as (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) did not affect Erk-1 or 2 activation at a concentration of 30 ?M. EGCG also inhibited the increase of VEGF expression and promoter activity induced by serum starvation. In the in vivo studies, athymic BALB/c nude mice were inoculated subcutaneously with HT29 cells and treated with daily intraperitoneal injections of EC (negative control) or EGCG at 1.5?mg day?1mouse?1starting 2 days after tumour cell inoculation. Treatment with EGCG inhibited tumour growth (58%), microvessel density (30%), and tumour cell proliferation (27%) and increased tumour cell apoptosis (1.9-fold) and endothelial cell apoptosis (3-fold) relative to the control condition (P< 0.05 for all comparisons). EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through blocking the induction of VEGF. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11259102

  14. Bisulfite or sulfite inhibits growth of Helicobacter pylori.

    PubMed Central

    Hawrylik, S J; Wasilko, D J; Haskell, S L; Gootz, T D; Lee, S E

    1994-01-01

    Bisulfite or sulfite was found to be inhibitory to Helicobacter pylori growth. A modified version of Brucella broth (BB), bisulfite-less BB (BLBB), supported rapid, robust, and consistent growth of H. pylori. We suggest that BLBB simply be called "Pylori broth" for distinction from Brucella broth. PMID:8195395

  15. Inhibition of human hair follicle growth by endo- and exocannabinoids

    Microsoft Academic Search

    Andrea Telek; T. Biro; Eniko ý Bodo ´; Balazs I. Toth; I. Borbiro; George Kunos; Ralf Paus

    2007-01-01

    Recent studies strongly suggest that the cannabinoid system is a key player in cell growth control. Since the organ-culture of human hair follicles (HF) offers an excellent, clinically relevant model for complex tissue interaction systems, we have asked whether the cannabinoid system plays a role in hair growth control. Here, we show that human scalp HF, intriguingly, are both targets

  16. The inhibition effect of some amino acids towards Pb–Sb–Se–As alloy corrosion in sulfuric acid solution

    Microsoft Academic Search

    Z. Ghasemi; A. Tizpar

    2006-01-01

    The inhibition effect of three amino acids towards the corrosion of Pb–Sb–Se–As alloy in 1.28 s.g. H2SO4 solution was investigated with linear polarization and weight loss measurements methods. The results drawn from two different techniques are comparable. The used amino acids were tryptophane, proline and methionine. The effect of inhibitor concentration and temperature against inhibitor action was investigated. It was

  17. Fungicides effectively used for growth inhibition of several fungi could induce mycotoxin biosynthesis in toxigenic species.

    PubMed

    Schmidt-Heydt, M; Stoll, D; Geisen, R

    2013-09-16

    Seven different commercial fungicides (Aliette, Rovral, Cantus, Ortiva, Luna Experience, Fenomenal and Mancozeb) were tested for their ability to inhibit the growth of the fungal species Penicillium nordicum, Penicillium verrucosum, Verticillium dahliae and Cladosporium sp. In case of the mycotoxigenic strains P. nordicum and P. verrucosum, the biosynthesis of the mycotoxins ochratoxin and citrinin was determined. Interestingly individual fungicides were only able to inhibit the growth of the analyzed fungi to some extent. In case of P. verrucosum the fungicide "Rovral", an iprodion belonging to the substance class of imidazoles, led to a decrease in the growth rate but to a strong induction of mycotoxin biosynthesis as has been described earlier for the strobilurins. Consequently before using a given fungicide to protect crops and enhance storage life, the applicability of this chemical compound should be tested not only for its ability to inhibit fungal growth but also for its effect on level of secondary metabolite biosynthesis. PMID:24036489

  18. Methyl anthranilate and ?-decalactone inhibit strawberry pathogen growth and achene Germination.

    PubMed

    Chambers, Alan H; Evans, Shane Alan; Folta, Kevin M

    2013-12-26

    Plant volatile compounds have been shown to affect microbial growth and seed germination. Here two fruity volatiles found in strawberry ( Fragaria × ananassa ), ?-decalactone ("peachlike" aroma) and methyl anthranilate ("grapelike" aroma), were tested for effects on relevant pathogens and seedling emergence. Significant growth reduction was observed for Botrytis cinerea , Colletotrichum gloeosporioides , Colletotrichum acutatum , Phomopsis obscurans , and Gnomonia fragariae at 1 mM ?-decalactone or methyl anthranilate, and 5 mM ?-decalactone or methyl anthranilate supplemented medium resulted in complete cessation of fungal growth. Phytophthora cactorum was especially sensitive to 1 mM ?-decalactone, showing complete growth inhibition. Bacteriostatic effects were observed in Xanthamonas cultures. Postharvest infestations on store-bought strawberries were inhibited with volatile treatment. The ?-decalactone volatile inhibited strawberry and Arabidopsis thaliana germination. These findings show that two compounds contributing to strawberry flavor may also contribute to shelf life and suggest that ?-decalactone may play an ecological role by preventing premature germination. PMID:24328200

  19. Inhibition of acid corrosion of aluminum using vanillin

    Microsoft Academic Search

    A. Y. El-Etre

    2001-01-01

    The inhibition efficiency (IE) of vanillin towards the corrosion of aluminum in 5 M HCl solution was measured using weight loss measurement, hydrogen evolution method, thermometry and potentiostatic polarization techniques. The results drawn from the different techniques are comparable and exhibit a small discrepancy. It was found that vanillin acts as a good inhibitor for the corrosion of aluminum in

  20. Boric acid reversibly inhibits the second step of pre-mRNA splicing Noam Shomron, Gil Ast

    E-print Network

    Ast, Gil

    Boric acid reversibly inhibits the second step of pre-mRNA splicing Noam Shomron, Gil Ast. This investigation demonstrates that the addi- tion of boric acid to an in vitro pre-mRNA splicing reaction causes words: Pre-mRNA splicing; Inhibition; Boric acid; Spliceosome 1. Introduction The spliceosome

  1. Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma

    PubMed Central

    Lamoureux, Francois; Baud'huin, Marc; Ory, Benjamin; Guiho, Romain; Zoubeidi, Amina; Gleave, Martin; Heymann, Dominique; Rédini, Françoise

    2014-01-01

    Purpose Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid (ZOL) represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, ZOL triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), which could enhance tumor cell survival and treatment resistance. We hypothesized that targeting CLU using siRNA or the antisense drug, OGX-011, will suppress treatment-induced CLU induction and enhance ZOL-induced cell death in osteosarcoma (OS) cells. Methods The combined effects of OGX-011 and ZOL were investigated in vitro on cell growth, viability, apoptosis and cell cycle repartition of ZOL-sensitive or -resistant human OS cell lines (SaOS2, U2OS, MG63 and MNNG/HOS). Results In OS cell lines, ZOL increased levels of HSPs, especially CLU, in a dose- and time-dependent manner by mechanism including increased HSF1 transcription activity. The OS resistant cells to ZOL exhibited higher CLU expression level than the sensitive cells. Moreover, CLU overexpression protects OS sensitive cells to ZOL-induced cell death by modulating the MDR1 and farnesyl diphosphate synthase expression. OGX-011 suppressed treatment-induced increases in CLU and synergistically enhanced the activity of ZOL on cell growth and apoptosis. These biologic events were accompanied by decreased expression of HSPs, MDR1 and HSF1 transcriptional activity. In vivo, OGX-011, administered 3 times a week (IP, 20mg/kg), potentiated the effect of ZOL (s.c; 50?g/kg), significantly inhibiting tumor growth by 50% and prolonging survival in MNNG/HOS xenograft model compared to ZOL alone. Conclusion These results indicate that ZOL-mediated induction of CLU can be attenuated by OGX-011, with synergistic effects on delaying progression of osteosarcoma. PMID:25138053

  2. Alpha Cyano-4-Hydroxy-3-Methoxycinnamic Acid Inhibits Proliferation and Induces Apoptosis in Human Breast Cancer Cells

    PubMed Central

    Hamdan, Lamia; Arrar, Zoheir; Al Muataz, Yacoub; Suleiman, Lutfi; Négrier, Claude; Mulengi, Joseph Kajima; Boukerche, Habib

    2013-01-01

    This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA), on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231) with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis) with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer. PMID:24039831

  3. Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells.

    PubMed

    Hamdan, Lamia; Arrar, Zoheir; Al Muataz, Yacoub; Suleiman, Lutfi; Négrier, Claude; Mulengi, Joseph Kajima; Boukerche, Habib

    2013-01-01

    This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA), on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231) with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis) with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer. PMID:24039831

  4. Fusion proteins of retinoid receptors antagonize TGF-?-induced growth inhibition of lung epithelial cells

    Microsoft Academic Search

    Ping La; Trish A Morgan; Stephen M Sykes; Hua Mao; Robert W Schnepp; Clark D Petersen; Xianxin Hua; X Hua

    2003-01-01

    Transforming growth factor-?1 (TGF-?) is a growth factor that has multiple functions including potent inhibition of cell growth. TGF-? signals by binding to its cell surface serine\\/threonine kinase receptors, which in turn phosphorylate downstream signal transducers, Smad2 and Smad3. Phosphorylated Smad2 and Smad3, together with Smad4, enter the nucleus and associate with various transcription factors. This complex of transcription factors

  5. Epoxygenase metabolites of arachidonic acid inhibit vasopressin response in toad bladder

    SciTech Connect

    Schlondorff, D.; Petty, E.; Oates, J.A.; Jacoby, M.; Levine, S.D. (Albert Einstein College of Medicine, Bronx, NY (USA) Vanderbilt Univ., Nashville, TN (USA))

    1987-09-01

    In addition to cyclooxygenase and lipoxygenase pathways, the kidney can also metabolize arachidonic acid by a NADPH-dependent cytochrome P-450 enzyme to epoxyeicosatrienoic acids (EETs); furthermore, 5,6-EET has been shown to alter electrolyte transport across isolated renal tubules. The authors examined the effects of three ({sup 14}C-labeled)-EETs (5,6-, 11,12-, and 14,15-EET) on osmotic water flow across toad urinary bladder. All three EETs reversibly inhibited vasopressin-stimulated osmotic water flow with 5,6- and 11,12-EET being the most potent. The effects appeared to be independent of prostaglandins EETs inhibited the water flow response to forskolin but not the response to adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) or 8-BrcAMP, consistent with an effect on cAMP generation. To determine whether these effects were due to the EETs or to products of their metabolism, they examined the effects of their vicinal diol hydrolysis products, the dihydroxyeicosatrienoic acids. Nonenzymatic conversion of labeled 5,6-EET to its vicinal diol occurred rapidly in the buffer, whereas 11,12-EET was hydrolyzed in a saturable manner only when incubated in the presence of bladder tissue. The dihydroxyeicosatrienoic acids formed inhibited water flow in a manner paralleling that of the EETs. The data support the hypothesis that EETs and their physiologically active dihydroxyeicosatrienoic acid metabolites inhibit vasopressin-stimulated water flow predominantly via inhibition of adenylate cyclase.

  6. Effects of potassium sorbate on growth and penicillic acid production by Aspergillus ochraceus and Penicillium aurantiogriseum.

    PubMed

    Garza, S; Canela, R; Viñas, I; Sanchis, V

    1993-08-01

    The effect of potassium sorbate on the growth and penicillin acid production of Aspergillus ochraceus and Penicillium aurantiogriseum was studied. Yeast extract sucrose (YES) broth at initial pH values of 5.5 or 7.0, and containing different concentrations of potassium sorbate was inoculated with fungal spores and incubated for 35 days at 28 degrees C. In all cases, although the pH changes in sorbate-containing media were delayed, patterns were similar to those of the cultures without sorbate. This was most evident when the highest concentration of potassium sorbate was used. Potassium sorbate also inhibited mycelial growth. Penicillic acid production was initially delayed by the presence of potassium sorbate but this inhibition was eventually overcome (30-35 days) and penicillic acid levels at the end of the experiment were similar or higher then the controls. Generally cultures growing in culture media at an initial pH of 5.5 produced less toxin than those growing at pH 7.0. PMID:8212939

  7. Bithionol inhibits ovarian cancer cell growth In Vitro - studies on mechanism(s) of action

    PubMed Central

    2014-01-01

    Background Drug resistance is a cause of ovarian cancer recurrence and low overall survival rates. There is a need for more effective treatment approaches because the development of new drug is expensive and time consuming. Alternatively, the concept of ‘drug repurposing’ is promising. We focused on Bithionol (BT), a clinically approved anti-parasitic drug as an anti-ovarian cancer drug. BT has previously been shown to inhibit solid tumor growth in several preclinical cancer models. A better understanding of the anti-tumor effects and mechanism(s) of action of BT in ovarian cancer cells is essential for further exploring its therapeutic potential against ovarian cancer. Methods The cytotoxic effects of BT against a panel of ovarian cancer cell lines were determined by Presto Blue cell viability assay. Markers of apoptosis such as caspases 3/7, cPARP induction, nuclear condensation and mitochondrial transmembrane depolarization were assessed using microscopic, FACS and immunoblotting methods. Mechanism(s) of action of BT such as cell cycle arrest, reactive oxygen species (ROS) generation, autotaxin (ATX) inhibition and effects on MAPK and NF-kB signalling were determined by FACS analysis, immunoblotting and colorimetric methods. Results BT caused dose dependent cytotoxicity against all ovarian cancer cell lines tested with IC50 values ranging from 19 ?M – 60 ?M. Cisplatin-resistant variants of A2780 and IGROV-1 have shown almost similar IC50 values compared to their sensitive counterparts. Apoptotic cell death was shown by expression of caspases 3/7, cPARP, loss of mitochondrial potential, nuclear condensation, and up-regulation of p38 and reduced expression of pAkt, pNF-?B, pI?B?, XIAP, bcl-2 and bcl-xl. BT treatment resulted in cell cycle arrest at G1/M phase and increased ROS generation. Treatment with ascorbic acid resulted in partial restoration of cell viability. In addition, dose and time dependent inhibition of ATX was observed. Conclusions BT exhibits cytotoxic effects on various ovarian cancer cell lines regardless of their sensitivities to cisplatin. Cell death appears to be via caspases mediated apoptosis. The mechanisms of action appear to be partly via cell cycle arrest, ROS generation and inhibition of ATX. The present study provides preclinical data suggesting a potential therapeutic role for BT against recurrent ovarian cancer. PMID:24495391

  8. Fatty acid synthase inhibition results in a magnetic resonance-detectable drop in phosphocholine

    PubMed Central

    Ross, James; Najjar, Amer M.; Sankaranarayanapillai, Madhuri; Tong, William P.; Kaluarachchi, Kumaralal; Ronen, Sabrina M.

    2008-01-01

    Expression of fatty acid synthase (FASN), the key enzyme in de novo synthesis of long-chain fatty acids (FA), is normally low but increases in cancer. Consequently, FASN is a novel target for cancer therapy. However, because FASN inhibitors can lead to tumor stasis rather than shrinkage, non-invasive methods for assessing FASN inhibition are needed. To this end, we combined 1H, 31P and 13C magnetic resonance spectroscopy (MRS) (i) to monitor the metabolic consequences of FASN inhibition and (ii) to identify MRS-detectable metabolic biomarkers of response. Treatment of PC-3 cells with the FASN inhibitor Orlistat for up to 48 h resulted in inhibition of FASN activity by 70%, correlating with 74% inhibition of FA synthesis. Furthermore, we have determined that FASN inhibition results not only in lower phosphatidylcholine levels, but also in a 59% drop in the phospholipid precursor phosphocholine (PCho). This drop resulted from inhibition in PCho synthesis as a result of a reduction in the cellular activity of its synthetic enzyme choline kinase. The drop in PCho levels following FASN inhibition was confirmed in SKOV-3 ovarian cancer cells treated with Orlistat and in MCF-7 breast cancer cells treated with Orlistat as well as cerulenin. Combining data from all treated cells, the drop in PCho significantly correlated with the drop in de novo synthesized FA levels, identifying PCho as a potential non-invasive MRS-detectable biomarker of FASN inhibition in vivo. PMID:18723500

  9. Ethacrynic Acid Butyl-Ester Induces Apoptosis in Leukemia Cells through a Hydrogen Peroxide-Mediated Pathway Independent ofGlutathione S-Transferase P1-1 Inhibition

    Microsoft Academic Search

    Rui Wang; Chunmin Li; Dandan Song; Guisen Zhao; Linxiang Zhao; Yongkui Jing

    2007-01-01

    Ethacrynic acid (EA), a glutathione S-transferase inhibitor and diuretic agent, inhibits cell growth and induces apoptosis in cancer cells. To improve the activities, the structure of EA has been modified, and it has been shown that EA esters had an increased cell growth inhibitory ability compared with nonesterified analogue. EA butyl-ester (EABE) was synthesized, and its apoptosis induction ability was

  10. Inhibition of breast cancer growth and metastasis by a biomimetic peptide

    PubMed Central

    Lee, Esak; Lee, Seung Jae; Koskimaki, Jacob E.; Han, Zheyi; Pandey, Niranjan B.; Popel, Aleksander S.

    2014-01-01

    Metastasis is the main cause of mortality in cancer patients. Though there are many anti-cancer drugs targeting primary tumor growth, anti-metastatic agents are rarely developed. Angiogenesis and lymphangiogenesis are crucial for cancer progression, particularly, lymphangiogenesis is pivotal for metastasis in breast cancer. Here we report that a novel collagen IV derived biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis. The peptide inhibits blood and lymphatic endothelial cell viability, migration, adhesion, and tube formation by targeting IGF1R and Met signals. The peptide blocks MDA-MB-231 tumor growth by inhibiting tumor angiogenesis in vivo. Moreover, the peptide inhibits lymphangiogenesis in primary tumors. MDA-MB-231 tumor conditioned media (TCM) was employed to accelerate spontaneous metastasis in tumor xenografts, and the anti-metastatic activity of the peptide was tested in this model. The peptide prevents metastasis to the lungs and lymph nodes by inhibiting TCM-induced lymphangiogenesis and angiogenesis in the pre-metastatic organs. In summary, a novel biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis in the pre-metastatic organs as well as primary tumors. PMID:25409905

  11. Dual effect of metformin on growth inhibition and oestradiol production in breast cancer cells.

    PubMed

    Rice, S; Pellat, L; Ahmetaga, A; Bano, G; Mason, H D; Whitehead, S A

    2015-04-01

    Evidence has been accumulating for a role for metformin in reducing breast cancer risk in post-menopausal women. It inhibits growth of breast cancer cells via several mechanisms, primarily the AMPK/mTOR signalling pathway. Another possible protective mechanism may be the ability of metformin to inhibit aromatase activity. In the present study, we investigated the effects of metformin on the basal growth of MCF-7 cells, after oestradiol (E2) stimulation and after the inhibition of mTOR by rapamycin. Secondly, we investigated the effects of metformin on the activity of a number of steroidogenic enzymes and the mRNA expression of aromatase and steroid sulphatase (STS). High doses of metformin significantly inhibited both basal and oestrogen-stimulated cell division. Low-dose rapamycin (10-10 M) did not inhibit growth, but the addition of metformin induced a significant reduction in growth. High-dose rapamycin (10-8 M) inhibited growth, and this was further attenuated by the addition of metformin. Exposure to low (10-7 M) and high (10-4 M) doses of metformin for 7-10 days significantly reduced the conversion of androstenedione (ANDRO) and testosterone (TESTO) (both requiring aromatase), but not the conversion of oestrone or oestrone sulphate (ES) via 17?-hydroxysteroid dehydrogenase/sulphatase to E2. This attenuation was via a downregulation in the expression of total aromatase mRNA and promoter II, whilst the expression of sulphatase was unaffected by metformin. In conclusion, plasma levels of metformin have a dual therapeutic action, first by directly inhibiting cell proliferation which can be augmented by rapamycin analogues, and secondly, by inhibiting aromatase activity and reducing the local conversion of androgens to E2. PMID:25716282

  12. Mono-(2-Ethylhexyl) Phthalate Induces Oxidative Stress and Inhibits Growth of Mouse Ovarian Antral Follicles1

    PubMed Central

    Wang, Wei; Craig, Zelieann R.; Basavarajappa, Mallikarjuna S.; Hafner, Katlyn S.; Flaws, Jodi A.

    2012-01-01

    ABSTRACT Mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of the most commonly used plasticizer, di-(2-ethylhexyl) phthalate, and is considered to be a reproductive toxicant. However, little is known about the effects of MEHP on ovarian antral follicles. Thus, the present study tested the hypothesis that MEHP inhibits follicle growth via oxidative stress pathways. The data indicate that MEHP increases reactive oxygen species (ROS) levels and inhibits follicle growth in antral follicles, whereas N-acetylcysteine (NAC; an antioxidant) restores ROS levels to control levels and rescues follicles from MEHP-induced inhibition of follicle growth. To further analyze the mechanism by which MEHP induces oxidative stress and inhibits follicle growth, the expression and activities of various key antioxidant enzymes (copper/zinc superoxide dismutase [SOD1], glutathione peroxidase [GPX], and catalase [CAT]) and the expression of key cell-cycle regulators (Ccnd2, Ccne1, and Cdk4) and apoptotic regulators (Bcl-2 and Bax) were compared in control and MEHP-treated follicles. The data indicate that MEHP inhibits the expression and activities of SOD1 and GPX; does not inhibit Cat expression; inhibits the expression of Ccnd2, Ccne1, Cdk4, and Bcl-2; but increases the expression of Bax compared to controls. Furthermore, NAC blocks these toxic effects of MEHP. Collectively, these data suggest that MEHP induces oxidative stress by disrupting the activities of antioxidant enzymes. This may lead to decreased expression of cell-cycle regulators and antiapoptotic regulators and increased expression of proapoptotic factors, which then may lead to inhibition of follicle growth. PMID:23077170

  13. Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of Apicomplexan Fab I

    Microsoft Academic Search

    Rima McLeod; Stephen P Muench; John B Rafferty; Dennis E Kyle; Ernest J Mui; Michael J Kirisits; Douglas G Mack; Craig W Roberts; Benjamin U Samuel; Russell E Lyons; Mark Dorris; Wilbur K Milhous; David W Rice

    2001-01-01

    Fab I, enoyl acyl carrier protein reductase (ENR), is an enzyme used in fatty acid synthesis. It is a single chain polypeptide in plants, bacteria, and mycobacteria, but is part of a complex polypeptide in animals and fungi. Certain other enzymes in fatty acid synthesis in apicomplexan parasites appear to have multiple forms, homologous to either a plastid, plant-like single

  14. Protease Inhibition by Oleic Acid Transfer From Chronic Wound Dressings to Albumin

    SciTech Connect

    Edwards, J. V.; Howley, Phyllis; Davis, Rachel M.; Mashchak, Andrew D.; Goheen, Steven C.

    2007-08-01

    High elastase and cathepsin G activities have been observed in chronic wounds. These levels can inhibit healing through degradation of growth factors, cytokines, and extracellular matrix proteins. Oleic acid (18:1) is a non-toxic elastase inhibitor with some potential for redressing the imbalance of elastase activity found in chronic wounds. Cotton wound dressing material was characterized as a transfer carrier for affinity uptake of 18:1 by albumin under conditions mimicking chronic wounds. 18:1-treated cotton was examined for its ability to bind and release the fatty acid in the presence of albumin. The mechanism of 18:1 uptake from cotton and binding by albumin was examined with both intact dressings and cotton fiber-designed chromatography. Raman spectra of the albumin-18:1 complexes under liquid-liquid equilibrium conditions revealed fully saturated albumin-18:1 complexes with a 1:1 weight ratio of albumin:18:1. Cotton chromatography under liquid-solid equilibrium conditions revealed oleic acid transfer from cotton to albumin at 27 mole equivalents of 18:1 per mole albumin. Cotton was contrasted with hydrogel, and hydrocolloid wound dressing for its comparative ability to lower elastase activity. Each dressing material evaluated was found to release 18:1 in the presence of albumin with significant inhibition of elastase activity. The 18:1-formulated wound dressings lowered elastase activity in a dose dependent manner in the order cotton gauze > hydrogel > hydrocolloid. In contrast the cationic serine protease Cathepsin G was inihibited by 18:1 within a narrow range of 18:1-cotton formulations. Four per cent Albumin solutions were most effective in binding cotton bound-18:1. However, 2% albumin was sufficient to transfer quantities of 18:1 necessary to achieve a significant elastase-lowering effect. Formulations with 128 mg 18:1/g cotton gauze had equivalent elastase lowering with 1 - 4% albumin. 18:1 bound to cotton wound dressings may have promise in the selective lowering of cationic serine protease activity useful in topical application for chronic inflammatory pathogenesis.

  15. Effects of humic acids on the growth of bacteria

    NASA Astrophysics Data System (ADS)

    Tikhonov, V. V.; Yakushev, A. V.; Zavgorodnyaya, Yu. A.; Byzov, B. A.; Demin, V. V.

    2010-03-01

    The influence of humic acids of different origins on the growth of bacterial cultures of different taxa isolated from the soil and the digestive tracts of earthworms ( Aporrectodea caliginosa)—habitats with contrasting conditions—was studied. More than half of the soil and intestinal isolates from the 170 tested strains grew on the humic acid of brown coal as the only carbon source. The specific growth rate of the bacteria isolated from the intestines of the earthworms was higher than that of the soil bacteria. The use of humic acids by intestinal bacteria confirms the possibility of symbiotic digestion by earthworms with the participation of bacterial symbionts. Humic acids at a concentration of 0.1 g/l stimulated the growth of the soil and intestinal bacteria strains (66 strains out of 161) on Czapek’s medium with glucose (1 g/l), probably, acting as a regulator of the cell metabolism. On the medium with the humic acid, the intestinal bacteria grew faster than the soil isolates did. The most active growth of the intestinal isolates was observed by Paenibacillus sp., Pseudomonas putida, Delftia acidovorans, Microbacterium terregens, and Aeromonas sp.; among the soil ones were the representatives of the Pseudomonas genus. A response of the bacteria to the influence of humic acids was shown at the strain level using the example of Pseudomonas representatives. The Flexom humin preparation stimulated the growth of the hydrocarbon-oxidizing Acinetobacter sp. bacteria. This effect can be used for creating a new compound with the elevated activity of bacteria that are destroyers of oil and oil products.

  16. A Kinetic Study of the Growth of Fatty Acid Vesicles

    PubMed Central

    Chen, Irene A.; Szostak, Jack W.

    2004-01-01

    Membrane vesicles composed of fatty acids can be made to grow and divide under laboratory conditions, and thus provide a model system relevant to the emergence of cellular life. Fatty acid vesicles grow spontaneously when alkaline micelles are added to buffered vesicles. To investigate the mechanism of this process, we used stopped-flow kinetics to analyze the dilution of non-exchanging FRET probes incorporated into preformed vesicles during growth. Oleate vesicle growth occurs in two phases (fast and slow), indicating two pathways for the incorporation of fatty acid into preformed vesicles. We propose that the fast phase, which is stoichiometrically limited by the preformed vesicles, results from the formation of a “shell” of fatty acid around a vesicle, followed by rapid transfer of this fatty acid into the preformed vesicle. The slower phase may result from incorporation of fatty acid which had been trapped in an intermediate state. We provide independent evidence for the rapid transformation of micelles into an aggregated intermediate form after transfer from high to low pH. Our results show that the most efficient incorporation of added oleate into oleic acid/oleate vesicles occurs under conditions that avoid a large transient increase in the micelle/vesicle ratio. PMID:15298905

  17. Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide

    NASA Technical Reports Server (NTRS)

    Betz, N. A.; Westhoff, B. A.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Our laboratory has purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) from intact bovine cerebral cortex cells. Evidence presented here demonstrates that sensitivity to CeReS-18-induced growth inhibition in BALB-c 3T3 cells is influenced by calcium, such that a decrease in the calcium concentration in the growth medium results in an increase in sensitivity to CeReS-18. Calcium did not alter CeReS-18 binding to its cell surface receptor and CeReS-18 does not bind calcium directly. Addition of calcium, but not magnesium, to CeReS-18-inhibited 3T3 cells results in reentry into the cell cycle. A greater than 3-hour exposure to increased calcium is required for escape from CeReS-18-induced growth inhibition. The calcium ionophore ionomycin could partially mimic the effect of increasing extracellular calcium, but thapsigargin was ineffective in inducing escape from growth inhibition. Increasing extracellular calcium 10-fold resulted in an approximately 7-fold increase in total cell-associated 45Ca+2, while free intracellular calcium only increased approximately 30%. However, addition of CeReS-18 did not affect total cell-associated calcium or the increase in total cell-associated calcium observed with an increase in extracellular calcium. Serum addition induced mobilization of intracellular calcium and influx across the plasma membrane in 3T3 cells, and pretreatment of 3T3 cells with CeReS-18 appeared to inhibit these calcium mobilization events. These results suggest that a calcium-sensitive step exists in the recovery from CeReS-18-induced growth inhibition. CeReS-18 may inhibit cell proliferation through a novel mechanism involving altering the intracellular calcium mobilization/regulation necessary for cell cycle progression.

  18. Dual inhibition of arachidonic acid pathway by mulberry leaf extract.

    PubMed

    Chauhan, Seema; Devi, Uma; Kumar, Venkatesh R; Kumar, Vikas; Anwar, Firoz; Kaithwas, Gaurav

    2015-02-01

    The present work investigates the anti-inflammatory, analgesic and antipyretic activity of methanolic extract of mulberry leaves of variety S-1, S-13 and S-146. The S-146 extract was further evaluated for its efficacy against adjuvant arthritis in albino rats followed by inhibitory potential for COX 1, COX 2 and 5 LOX. The HPLC analysis enumerated the presence of morin, reversterol, scopoletin and 7-hydroxy coumarin as the major constituents. The anti-inflammatory, antipyretic and analgesic activity observed in the present experiment could be accredited to the dual inhibition in the AA pathway. The inhibition of COX and LOX enzymes could be imparted to the presence of resveraterol, morin, scopoletin and 7-hydroxy coumarin. PMID:25490949

  19. Bisphenol A inhibits cultured mouse ovarian follicle growth partially via the aryl hydrocarbon receptor signaling pathway

    PubMed Central

    Ziv-Gal, Ayelet; Craig, Zelieann R.; Wang, Wei; Flaws, Jodi A.

    2013-01-01

    Bisphenol A (BPA) is an endocrine disruptor that inhibits growth of mouse ovarian follicles and disrupts steroidogenesis at a dose of 438 ?M. However, the effects of lower doses of BPA and its mechanism of action in ovarian follicles are unknown. We hypothesized that low doses of BPA inhibit follicular growth and decrease estradiol levels through the aryl hydrocarbon receptor (AHR) pathway. Antral follicles from wild-type and Ahr knock-out (AhrKO) mice were cultured for 96 hours. Follicle diameters and estradiol levels then were compared in wild-type and AhrKO follicles ± BPA (0.004 - 438 ?M). BPA inhibited follicle growth (110 - 438 ?M) and decreased estradiol levels (43.8 - 438 ?M) in wild-type and AhrKO follicles. However, at BPA 110 ?M, inhibition of growth in AhrKO follicles was attenuated compared to wild-type follicles. These data suggest that BPA may inhibit follicle growth partially via the AHR pathway, whereas its effects on estradiol synthesis likely involve other mechanisms. PMID:23928317

  20. Growth Arrest on Inhibition of Nonsense-Mediated Decay Is Mediated by Noncoding RNA GAS5

    PubMed Central

    Mourtada-Maarabouni, Mirna; Williams, Gwyn T.

    2013-01-01

    Nonsense-mediated decay is a key RNA surveillance mechanism responsible for the rapid degradation of mRNAs containing premature termination codons and hence prevents the synthesis of truncated proteins. More recently, it has been shown that nonsense-mediated decay also has broader significance in controlling the expression of a significant proportion of the transcriptome. The importance of this mechanism to the mammalian cell is demonstrated by the observation that its inhibition causes growth arrest. The noncoding RNA growth arrest specific transcript 5 (GAS5) has recently been shown to play a key role in growth arrest induced by several mechanisms, including serum withdrawal and treatment with the mTOR inhibitor rapamycin. Here we show that inhibition of nonsense-mediated decay in several human lymphocyte cell lines causes growth arrest, and siRNA-mediated downregulation of GAS5 in these cells significantly alleviates the inhibitory effects observed. These observations hold true for inhibition of nonsense-mediated decay both through RNA interference and through pharmacological inhibition by aminoglycoside antibiotics gentamycin and G418. These studies have important implications for ototoxicity and nephrotoxicity caused by gentamycin and for the proposed use of NMD inhibition in treating genetic disease. This report further demonstrates the critical role played by GAS5 in the growth arrest of mammalian cells. PMID:24319682

  1. BRD4 Inhibitor Inhibits Colorectal Cancer Growth and Metastasis

    PubMed Central

    Hu, Yuan; Zhou, Jieqiong; Ye, Fei; Xiong, Huabao; Peng, Liang; Zheng, Zihan; Xu, Feihong; Cui, Miao; Wei, Chengguo; Wang, Xinying; Wang, Zhongqiu; Zhu, Hongfa; Lee, Peng; Zhou, Mingming; Jiang, Bo; Zhang, David Y.

    2015-01-01

    Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal. PMID:25603177

  2. Inhibition of the growth of Bacillus subtilis DSM10 by a newly discovered antibacterial protein from the soil metagenome.

    PubMed

    O'Mahony, Mark M; Henneberger, Ruth; Selvin, Joseph; Kennedy, Jonathan; Doohan, Fiona; Marchesi, Julian R; Dobson, Alan D W

    2015-03-01

    A functional metagenomics based approach exploiting the microbiota of suppressive soils from an organic field site has succeeded in the identification of a clone with the ability to inhibit the growth of Bacillus subtilis DSM10. Sequencing of the fosmid identified a putative ?-lactamase-like gene abgT. Transposon mutagenesis of the abgT gene resulted in a loss in ability to inhibit the growth of B. subtilis DSM10. Further analysis of the deduced amino acid sequence of AbgT revealed moderate homology to esterases, suggesting that the protein may possess hydrolytic activity. Weak lipolytic activity was detected; however the clone did not appear to produce any ?-lactamase activity. Phylogenetic analysis revealed the protein is a member of the family VIII group of lipase/esterases and clusters with a number of proteins of metagenomic origin. The abgT gene was sub-cloned into a protein expression vector and when introduced into the abgT transposon mutant clones restored the ability of the clones to inhibit the growth of B. subtilis DSM10, clearly indicating that the abgT gene is involved in the antibacterial activity. While the precise role of this protein has yet to fully elucidated, it may be involved in the generation of free fatty acid with antibacterial properties. Thus functional metagenomic approaches continue to provide a significant resource for the discovery of novel functional proteins and it is clear that hydrolytic enzymes, such as AbgT, may be a potential source for the development of future antimicrobial therapies. PMID:25692994

  3. Salicylic acid mediates the reduced growth of lignin down-regulated plants.

    PubMed

    Gallego-Giraldo, Lina; Escamilla-Trevino, Luis; Jackson, Lisa A; Dixon, Richard A

    2011-12-20

    Down-regulation of the enzyme hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase (HCT) in thale cress (Arabidopsis thaliana) and alfalfa (Medicago sativa) leads to strongly reduced lignin levels, reduced recalcitrance of cell walls to sugar release, but severe stunting of the plants. Levels of the stress hormone salicylic acid (SA) are inversely proportional to lignin levels and growth in a series of transgenic alfalfa plants in which lignin biosynthesis has been perturbed at different biosynthetic steps. Reduction of SA levels by genetically blocking its formation or causing its removal restores growth in HCT-down-regulated Arabidopsis, although the plants maintain reduced lignin levels. SA-mediated growth inhibition may occur via interference with gibberellic acid signaling or responsiveness. Our data place SA as a central component in growth signaling pathways that either sense flux into the monolignol pathway or respond to secondary cell-wall integrity, and indicate that it is possible to engineer plants with highly reduced cell-wall recalcitrance without negatively impacting growth. PMID:22123972

  4. Salicylic acid mediates the reduced growth of lignin down-regulated plants

    PubMed Central

    Gallego-Giraldo, Lina; Escamilla-Trevino, Luis; Jackson, Lisa A.; Dixon, Richard A.

    2011-01-01

    Down-regulation of the enzyme hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase (HCT) in thale cress (Arabidopsis thaliana) and alfalfa (Medicago sativa) leads to strongly reduced lignin levels, reduced recalcitrance of cell walls to sugar release, but severe stunting of the plants. Levels of the stress hormone salicylic acid (SA) are inversely proportional to lignin levels and growth in a series of transgenic alfalfa plants in which lignin biosynthesis has been perturbed at different biosynthetic steps. Reduction of SA levels by genetically blocking its formation or causing its removal restores growth in HCT–down-regulated Arabidopsis, although the plants maintain reduced lignin levels. SA-mediated growth inhibition may occur via interference with gibberellic acid signaling or responsiveness. Our data place SA as a central component in growth signaling pathways that either sense flux into the monolignol pathway or respond to secondary cell-wall integrity, and indicate that it is possible to engineer plants with highly reduced cell-wall recalcitrance without negatively impacting growth. PMID:22123972

  5. Vitamin K enhancement of sorafenib-mediated HCC cell growth inhibition in vitro and in vivo.

    PubMed

    Wei, Gang; Wang, Meifang; Hyslop, Terry; Wang, Ziqiu; Carr, Brian I

    2010-12-15

    The multikinase inhibitor sorafenib is the first oral agent to show activity against human hepatocellular carcinoma (HCC). Apoptosis has been shown to be induced in HCC by several agents, including sorafenib as well as by the naturally occurring K vitamins (VKs). As few nontoxic agents have activity against HCC growth, we evaluated the activity of sorafenib and VKs, both independently and together on the growth of HCC cells in vitro and in vivo. We found that when VK was combined with sorafenib, the concentration of sorafenib required for growth inhibition was substantially reduced. Conversely, VK enhanced sorafenib effects in several HCC cell lines on growth inhibition. Growth could be inhibited at doses of VK plus sorafenib that were ineffective with either agent alone, using vitamins K1, K2 and K5. Combination of VK1 plus sorafenib induced apoptosis on FACS, TUNEL staining and caspase activation. Phospho-extracellular signal-regulated kinase (ERK) levels were decreased as was myeloid cell leukemia sequence 1 (Mcl-1), an ERK target. Sorafenib alone inhibited growth of transplantable HCC in vivo. At subeffective sorafenib doses in vivo, addition of VK1 caused major tumor regression, with decreased phospho-ERK and Mcl-1 staining. Thus, combination of VK1 plus sorafenib strongly induced growth inhibition and apoptosis in rodent and human HCC and inhibited the RAF/mitogen-activated protein kinase kinase/ERK pathway. VK1 alone activated PKA, a mediator of inhibitory Raf phosphorylation. Thus, each agent can antagonize Raf: sorafenib as a direct inhibitor and VK1 through inhibitory Raf phosphorylation. As both agents are available for human use, the combination has potential for improving sorafenib effects in HCC. PMID:21351273

  6. Vitamin K enhancement of Sorafenib-mediated HCC cell growth inhibition in vitro and in vivo

    PubMed Central

    Wei, Gang; Wang, Meifanf; Hyslop, Terry; Wang, Ziqiu; Carr, Brian I.

    2010-01-01

    The multi-kinase inhibitor Sorafenib, is the first oral agent to show activity against human hepatocellular carcinoma (HCC). Apoptosis has been shown to be induced in HCC by several agents, including Sorafenib, as well as by the naturally occurring K vitamins (VKs). Since few non toxic agents have activity against HCC growth, we evaluated the activity of Sorafenib and K vitamins, both independently and together on the growth in vitro and in vivo of HCC cells. We found that when VK was combined with Sorafenib, the concentration of Sorafenib required for growth inhibition was substantially reduced. Conversely, VK enhanced Sorafenib effects in several HCC cell lines on growth inhibition. Growth could be inhibited at doses of VK plus Sorafenib that were ineffective with either agent alone,using vitamins K1, K2 and K5. Combination VK1 plus Sorafenib induced apoptosis on FACS, TUNEL staining and caspase activation. Phospho-ERK levels were decreased, as was Mcl-1, an ERK target. Sorafenib alone inhibited growth of transplantable HCC in vivo. At sub-effective Sorafenib doses in vivo, addition of VK1 caused major tumor regression, with decreased phospho-ERK and Mcl-1 staining. Thus, combination VK1 plus Sorafenib strongly induced growth inhibition and apoptosis in rodent and human HCC and inhibited the RAF/MEK/ERK pathway. VK1 alone activated PKA, a mediator of inhibitory Raf phosphorylation. Thus, each agent can antagonize Raf; Sorafenib as a direct inhibitor and VK1 through inhibitory Raf phosphorylation. Since both agents are available for human use, the combination has potential for improving Sorafenib effects in HCC. PMID:21351273

  7. Studies on the Inhibitive Effect of 3-HYDROXYFLAVONE on the Acid Corrosion of Mild Steel

    NASA Astrophysics Data System (ADS)

    Lavanya, Muthu Nadar; Kesavan, Devarayan; Prabhavathi, Nagarajan; Sulochana, Nagarajan

    The corrosion inhibition effect of 3-hydroxyflavone was studied on mild steel in 1 M hydrochloric acid (HCl). The anticorrosive effect was evaluated by weight loss and electrochemical methods which include Tafel polarization and AC impedance studies at 300 K. In weight loss method, the inhibition efficiency increased with increase in inhibitor concentration, and decreased with increase in temperature and immersion time, and acid concentration. The inhibitor showed maximum efficiency of 91% at 4 × 10-4 M concentration in 1 M hydrochloric acid. The Tafel polarization study showed that the inhibitor behaves likely as cathodic type. The corrosion inhibition effect measured by weight loss method and electrochemical studies was in good agreement with each other. The surface analysis was done by using scanning electron microscope (SEM). Several adsorption isotherms are assessed to study the adsorption behavior of the inhibitor on the mild steel surface. The negative value of ?Gads indicates the spontaneous adsorption of the inhibitor on mild steel surface.

  8. Indole3-butyric acid in plant growth and development

    Microsoft Academic Search

    Jutta Ludwig-Müller

    2000-01-01

    Within the last ten years it has been established by GC-MS thatindole-3-butyric acid (IBA) is an endogenous compound in a variety ofplant species. When applied exogenously, IBA has a variety of differenteffects on plant growth and development, but the compound is stillmainly used for the induction of adventitious roots. Using moleculartechniques, several genes have been isolated that are induced duringadventitious

  9. GROWTH OF CAMPYLOBACTER ON MEDIA SUPPLEMENTED WITH ORGANIC ACIDS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Campylobacter spp. are the main cause of bacterial foodborne illnesses in humans, and contaminated poultry products are major sources of campylobacteriosis. In this study, the growth of Campylobacter spp. in media supplemented with organic acids was examined. Tryptose-yeast extract basal broth mediu...

  10. Galbanic acid inhibits HIF-1? expression via EGFR/HIF-1? pathway in cancer cells.

    PubMed

    Eskandani, Morteza; Abdolalizadeh, Jalal; Hamishehkar, Hamed; Nazemiyeh, Hossein; Barar, Jaleh

    2015-03-01

    Hypoxia Inducible Factor-1 plays a key transcriptional role in the adaptation of hypoxic solid tumors to low oxygen environment. Here, we aimed to investigate galbanic acid (GBA) inhibitory effects on HIF-1 activation during hypoxia and normoxia. MTT survival and Annexin V assays were used to evaluate GBA cytotoxicity and apoptosis in treated cells. Quantitative real time PCR and western blotting were used to estimate mRNA expression and translated protein, respectively. Results showed that GBA dose- and time-dependently decreased the in vitro growth of OVCAR-3 human epithelial carcinoma cells with an IC50 of approximately 37, 12.1 and 10?M GBA at 24, 48 and 72h, respectively. Following phosphatidylserine of outer leaflet of the plasma membrane revealed occurrence of early/late apoptosis in GBA treated cells. In addition, we found that GBA down-regulates HIF-1? and HIF-1? mRNA expression in both hypoxia and normoxia. To determine the mechanism of action, we showed that GBA did not inhibit Akt and EGFR mRNA expression, yet protein degradation investigation showed that GBA shortened the half-life of EGFR through decreasing its stability with a decrease of nearly 2 and 3h in A549 and OVCAR-3 cell lines, respectively. We also found that downstream genes contributed in glycolysis, including Eno 1 and GluT-1, are underexpressed in GBA treated cells in hypoxia. Conclusively, GBA may inhibit HIF-1 activation through down-regulation of its subunit expression in hypoxia, and increasing of EGFR degradation in normoxia. PMID:25510323

  11. Inhibition of protein synthesis may explain the bactericidal properties of hypochlorous acid produced by phagocytic cells

    Microsoft Academic Search

    S. M. McKenna; K. J. A. Davies

    1986-01-01

    The authors find that hypochlorous acid (HOCl) and hydrogen peroxide (HâOâ) inhibit protein synthesis in E. coli: HOCl is similarly ordered 10x more efficient than HâOâ. This result may underlie the mechanism of bacterial killing by phagocytes, which use HâOâ and myeloperoxidase (MPO) to oxidize Cl⁻ to HOCl. Protein synthesis (³H-leu incorporation) was completely inhibited by 50..mu..M HOCl, whereas 50..mu..M

  12. Synergistic inhibition between o-phenanthroline and chloride ion for steel corrosion in sulphuric acid

    Microsoft Academic Search

    Xueming Li; Libin Tang; Lin Li; Guannan Mu; Guangheng Liu

    2006-01-01

    The corrosion inhibition of cold rolled steel in 0.5M sulphuric acid in the presence of o-phenanthroline and sodium chloride (NaCl) has been investigated by using weight loss and electrochemical techniques. The experimental data suggest that the inhibition efficiency increases with increasing NaCl concentration in the presence of 0.0002M o-phenanthroline, but decreases with increasing temperature. A synergistic effect is observed when

  13. The inhibitive effect of hexamethylenetetramine on the acid corrosion of steel

    Microsoft Academic Search

    E. Bayol; K. Kayak?r?lmaz; M. Erbil

    2007-01-01

    The efficiency of hexamethylenetetramine (HMTA), as corrosion inhibitors for steel in de-aerated 0.3M HCl, 0.1M H2SO4 and 0.1M H2SO4+1.0×10?3M HCl solutions have been determined by electrochemical studies. It was found that the HMTA acts a good corrosion inhibitor for steel corrosion in acids solutions. Increase in inhibition efficiency with the increase of concentrations of HMTA shows that inhibition actions are

  14. A Systems Chemical Biology Study of Malate Synthase and Isocitrate Lyase Inhibition in Mycobacterium tuberculosis During Active and NRP Growth

    PubMed Central

    May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander; Oprea, Tudor I.

    2013-01-01

    The ability of Mycobacterium tuberculosis (Mtb) to survive in low oxygen environments enables the bacterium to persist in a latent state within host tissues. In vitro studies of Mtb growth have identified changes in isocitrate lyase (ICL) and malate synthase (MS) that enable bacterial persistent under low oxygen and other environmentally limiting conditions. Systems chemical biology (SCB) enables us to evaluate the effects of small molecule inhibitors not only on the reaction catalyzed by malate synthase and isocitrate lyase, but the effect on the complete tricarboxylic acid cycle (TCA) by taking into account complex network relationships within that system. To study the kinetic consequences of inhibition on persistent bacilli, we implement a systems-chemical biology (SCB) platform and perform a chemistry-centric analysis of key metabolic pathways believed to impact Mtb latency. We explore consequences of disrupting the function of malate synthase (MS) and isocitrate lyase (ICL) during aerobic and hypoxic non-replicating persistence (NRP) growth by using the SCB method to identify small molecules that inhibit the function of MS and ICL, and simulating the metabolic consequence of the disruption. Results indicate variations in target and non-target reaction steps, clear differences in the normal and low oxygen models, as well as dosage dependent response. Simulation results from singular and combined enzyme inhibition strategies suggest ICL may be the more effective target for chemotherapeutic treatment against Mtb growing in a microenvironment where oxygen is slowly depleted, which may favor persistence. PMID:24121675

  15. Growth of nisin-producing lactococci in cooked rice supplemented with soybean extract and its application to inhibition of Bacillus subtilis in rice miso.

    PubMed

    Kato, T; Inuzuka, L; Kondo, M; Matsuda, T

    2001-02-01

    Lactic acid fermentation of cooked rice and rice koji by supplementation with soybean extract (SBE) and its application to rice miso fermentation were investigated. By supplementing the cooked rice with SBE, lactic acid bacteria (LAB) grew well without any unfavorable effects on the rice such as off-flavor or coloration. Lactococcus lactis subsp. lactis IFO12007 (Lc. lactis, a producer of the bacteriocin nisin) proliferated at 10(8 to approximately 9) cells/g after 24 h of incubation and produced high activity of nisin. The fermented rice with Lc. lactis strongly inhibited not only Bacillus subtilis ATCC19659 but also the other Bacillus strains. While some strains of LAB markedly inhibited the growth of Asp. oryzae, resulting in failure of koji fermentation, Lc. lactis did not affect the growth of these molds. When Lc. lactis was used for rice miso fermentation as a lactic acid starter culture, Lc. lactis rapidly proliferated and produced high nisin activity of 6,400 IU/g, in the steamed rice, resulting in complete growth inhibition of B. subtilis, which had been inoculated at the beginning of the koji fermentation. The rice miso after 12 weeks of aging had a suitable pH, and favorable taste and color. Furthermore, hyposalting of rice miso could be done without difficulty by lactic acid fermentation of both rice and soybeans. PMID:11302166

  16. The inhibition effect of some amino acids towards Pb Sb Se As alloy corrosion in sulfuric acid solution

    NASA Astrophysics Data System (ADS)

    Ghasemi, Z.; Tizpar, A.

    2006-03-01

    The inhibition effect of three amino acids towards the corrosion of Pb-Sb-Se-As alloy in 1.28 s.g. H 2SO 4 solution was investigated with linear polarization and weight loss measurements methods. The results drawn from two different techniques are comparable. The used amino acids were tryptophane, proline and methionine. The effect of inhibitor concentration and temperature against inhibitor action was investigated. It was found that these inhibitors act as good inhibitors for the corrosion of lead alloy in H 2SO 4 solution. Increasing inhibitor concentration increases the inhibition efficiency. It was found that adsorption of used amino acids on lead alloy surface follows Langmuir isotherm.

  17. GSK1904529A, an insulin?like growth factor?1 receptor inhibitor, inhibits glioma tumor growth, induces apoptosis and inhibits migration.

    PubMed

    Zhou, Qiang; Zhang, Junxia; Cui, Qinying; Li, Xiaodong; Gao, Ge; Wang, Yanfen; Xu, Yuping; Gao, Xiaoqun

    2015-09-01

    Malignant gliomas are the most common type of primary malignancy of the central nervous system, with a poor prognosis. The therapeutic options for malignant gliomas are limited and far from satisfactory, and novel treatment strategies are urgently required to improve the outcome of the disease. Insulin?like growth factor (IGF)/IGF?1 receptor (IGF?1R) signaling pathway regulates cell proliferation, motility and survival. The dysregulation of this signaling pathway has been implicated in the development of malignant gliomas. In the present study, GSK1904529A, a small molecule inhibitor of IGF?1R, suppressed glioma cell viability, induced glioma cell apoptosis and inhibited glioma cell migration in vitro. In addition, GSK1904529A inhibited glioma tumor growth and induced tumor cell apoptosis in vivo. In conclusion, the results of the present study suggested GSK1904529A as a promising agent for the treatment of malignant glioma. PMID:26035416

  18. Inhibition of nitrogen fixation in alfalfa by arsenate, heavy metals, fluoride, and simulated acid rain

    SciTech Connect

    Porter, J.R.; Sheridan, R.P.

    1981-07-01

    The acute effects of aqueous solutions of As, Cd, Cu, Pb, F, and Zn ions at concentrations from 0.01 to 100 micrograms per milliliter and solutions adjusted to pH 2 to 6 with nitric or sulfuric acid were studied with respect to acetylene reduction, net photosynthesis, respiration rate, and chlorophyll content in Vernal alfalfa. The effects of the various treatments on acetylene reduction varied from no demonstrable effect by any concentration of F/sup -/ and 42% inhibition by 100 micrograms Pb/sup 2 +/ per milliliter, to 100% inhibition by 10 micrograms Cd/sup 2 +/ per milliliter and 100 micrograms per milliliter As, Cu/sup 2 +/, and Zn/sup 2 +/ showed statistically significant inhibition of activity at 0.1 micrograms per milliliter. Acid treatments were not inhibitory above pH 2, at which pH nitric acid inhibited acetylene reduction activity more than did sulfuric acid. The inhibition of acetylene reduction by these ions was Zn/sup 2 +/ > Cd/sup 2 +/ > Cu/sup 2 +/ > AsO/sub 3//sup -/ > F/sup -/. The sensitivity of acetylene reduction to the ions was roughly equal to the sensitivity of photosynthesis, respiration, and chlorophyll content when Pb/sup 2 +/ was applied, but was 1000 times more sensitive to Zn/sup 2 +/. The relationship of the data to field conditions and industrial pollution is discussed.

  19. Protocatechuic acid alkyl esters: hydrophobicity as a determinant factor for inhibition of NADPH oxidase.

    PubMed

    de Faria, C M Q G; Nazaré, A C; Petrônio, M S; Paracatu, L C; Zeraik, M L; Regasini, L O; Silva, D H S; da Fonseca, L M; Ximenes, V F

    2012-01-01

    This study presents the increased efficiency of NADPH oxidase inhibition produced by esterification of protocatechuic acid (P0). Alkyl esters bearing chain lengths of 4 (P4), 7 (P7) and 10 (P10) carbons were synthesized and their oxidation potential, hydrophobicity, antiradical activity, inhibition of superoxide anion (O2°(-)), and the abilities to affect hypochlorous acid (HOCl) production by leukocytes and inhibit myeloperoxidase (MPO) chlorinating activity were studied. The increased hydrophobicity (logP, 0.81-4.82) of the esters was not correlated with a significant alteration in their oxidation potential (0.222-0.298 V). However, except for P10, the esters were ~ 2-fold more effective than the acid precursor for the scavenging of DPPH and peroxyl radicals. The esters were strong inhibitors of O2°(-) released by activated neutrophils (PMNs) and peripheral blood mononuclear cells (PBMCs). A correlation was found between the carbon chain length and the relative inhibitory potency. P7, the most active ester, was ~ 10-fold more efficient as NADPH oxidase inhibitor than apocynin. The esters strongly inhibited the release of HOCl by PMNs, which was a consequence of the inhibition of NADPH oxidase activity in these cells. In conclusion, as effective inhibitors of NADPH oxidase, the esters of protocatechuic acid are promising drugs for treatment of chronic inflammatory diseases. Moreover, this is the first demonstration that, besides the redox active moiety, the hydrophobicity can also be a determinant factor for the design of NADPH oxidase inhibitors. PMID:22934778

  20. Maternal amino acid supplementation for intrauterine growth restriction.

    PubMed

    Brown, Laura D; Green, Alice S; Limesand, Sean W; Rozance, Paul J

    2011-01-01

    Maternal dietary protein supplementation to improve fetal growth has been considered as an option to prevent or treat intrauterine growth restriction. However, in contrast to balanced dietary supplementation, adverse perinatal outcomes in pregnant women who received high amounts of dietary protein supplementation have been observed. The responsible mechanisms for these adverse outcomes are unknown. This review will discuss relevant human and animal data to provide the background necessary for the development of explanatory hypotheses and ultimately for the development therapeutic interventions during pregnancy to improve fetal growth. Relevant aspects of fetal amino acid metabolism during normal pregnancy and those pregnancies affected by IUGR will be discussed. In addition, data from animal experiments which have attempted to determine mechanisms to explain the adverse responses identified in the human trials will be presented. Finally, we will suggest new avenues for investigation into how amino acid supplementation might be used safely to treat and/or prevent IUGR. PMID:21196387

  1. Design, synthesis, and biological evaluation of aminoboronic acids as growth-factor receptor inhibitors of EGFR and VEGFR-1 tyrosine kinases.

    PubMed

    Asano, Toru; Nakamura, Hiroyuki; Uehara, Yoshimasa; Yamamoto, Yoshinori

    2004-04-01

    A series of aminoboronic acids was synthesized based on the structure of lavendustin pharmacophore 1. Their inhibitory activities against the epidermal growth-factor receptor (EGFR) and vascular endothelial growth-factor receptor-1 (VEGFR-1, Flt-1) protein tyrosine kinases, and various protein kinases, PKA, PKC, PTK, and eEF2K were evaluated. Selective inhibition activities were observed in a series of aminoboronic acids. 4-Methoxy-3-((2- methoxyphenylamino)methyl)phenylboronic acid 10 inhibited EGFR tyrosine kinase, whereas 4-(2,5-dihydroxybenzylamino)phenylboronic acid 12 inhibited Flt-1 protein kinase, although lavendustin pharmacophore 1 inhibited both EGFR and Flt-1 kinases at a compound concentration of 1.0 microg mL(-1). The selective inhibition of EGFR by 10 is considered to be due to the substitution of the dihydroxy groups on the benzyl moiety for a boronic acid group at the para position, whereas the selective inhibition of Flt-1 by 12 is due to the substitution of the carboxyl group on the aniline moiety in the lavendustin pharmacophore 1 for a boronic acid group. PMID:15185372

  2. Effusanin E Suppresses Nasopharyngeal Carcinoma Cell Growth by Inhibiting NF-?B and COX-2 Signaling

    PubMed Central

    Zhuang, Mingzhu; Zhao, Mouming; Qiu, Huijuan; Shi, Dingbo; Wang, Jingshu; Tian, Yun; Lin, Lianzhu; Deng, Wuguo

    2014-01-01

    Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC) cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-?B proteins. Moreover, effusanin E abrogated the binding of NF-?B to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-?B-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate) had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-?B/COX-2 (lipopolysaccharides) abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-?B and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma. PMID:25333664

  3. Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-?B and COX-2 signaling.

    PubMed

    Zhuang, Mingzhu; Zhao, Mouming; Qiu, Huijuan; Shi, Dingbo; Wang, Jingshu; Tian, Yun; Lin, Lianzhu; Deng, Wuguo

    2014-01-01

    Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC) cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-?B proteins. Moreover, effusanin E abrogated the binding of NF-?B to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-?B-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate) had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-?B/COX-2 (lipopolysaccharides) abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-?B and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma. PMID:25333664

  4. Profilin inhibits pollen tube growth through actin-binding, but not poly-l-proline-binding

    Microsoft Academic Search

    Sylvester T. McKenna; Luis Vidali; Peter K. Hepler

    2004-01-01

    Previously, we have shown that excess profilin inhibits pollen tube growth at significantly lower concentrations than it blocks cytoplasmic streaming. To elucidate the mechanism by which profilin achieves this function, we have employed mutant profilins from Schizosaccharomyces pombe [J. Lu and T.D. Pollard (2001) Mol Biol Cell 12:1161–1175], which have defects in actin-binding, ability to inhibit polymerization, and poly-l-proline (PLP)-binding.

  5. Activation of Liver X Receptors inhibits of Hedgehog signaling, clonogenic growth, and self-renewal in multiple myeloma

    PubMed Central

    Agarwal, Jasmin R.; Wang, Qiuju; Tanno, Toshihiko; Rasheed, Zeshaan; Merchant, Akil; Ghosh, Nilanjan; Borrello, Ivan; Huff, Carol Ann; Parhami, Farhad; Matsui, William

    2014-01-01

    The Hedgehog (Hh) signaling pathway is aberrantly activated in a wide variety of human cancers, and recent clinical studies have demonstrated that pathway inhibitors are effective in advanced basal cell carcinoma (BCC). The majority of these agents have been designed to target SMOOTHENED (SMO), a transmembrane regulator of Hh signaling, but subsequent mutations in SMO have been found to generate drug resistance. In other cancers, oncogenic events that bypass SMO may activate canonical Hh signaling, and SMO antagonists have not demonstrated significant activity in several diseases. Therefore, alternative strategies targeting the Hh pathway downstream of SMO may have clinical utility. Liver X Receptors (LXRs) regulate cholesterol and fatty acid homeostasis, and LXR activation can inhibit the Hh pathway in normal mouse embryonic fibroblasts. We examined the effects of LXR activation on Hh signaling in human multiple myeloma (MM) cells and found that LXR agonists inhibited Hh pathway activity and clonogenic tumor growth in vitro. LXR activation also inhibited putative MM cancer stem cells in vivo leading to the loss of tumor initiating and self-renewal potential. Finally, Hh signaling was inhibited downstream of SMO, suggesting that LXR agonists may represent a novel strategy to target pathogenic Hh signaling as well as treat MM. PMID:24807964

  6. Inhibition of tubulin polymerization by hypochlorous acid and chloramines

    Microsoft Academic Search

    Lisa M. Landino; Tara D. Hagedorn; Shannon B. Kim; Katherine M. Hogan

    2011-01-01

    Protein thiol oxidation and modification by nitric oxide and glutathione are emerging as common mechanisms to regulate protein function and to modify protein structure. Also, thiol oxidation is a probable outcome of cellular oxidative stress and is linked to degenerative disease progression. We assessed the effect of the oxidants hypochlorous acid and chloramines on the cytoskeletal protein tubulin. Total cysteine

  7. Inhibition of Dendritic Cell Differentiation by Fumaric Acid Esters

    Microsoft Academic Search

    Kejian Zhu; Ulrich Mrowietz

    2001-01-01

    Fumaric acid esters have proved to be effective for the systemic treatment of severe psoriasis vulgaris. These compounds have been shown to induce a Th2-like cytokine secretion pattern in T cells and to reduce keratinocyte proliferation in vitro. Dendritic cells seem to be of major importance as regulatory cells driving the psoriatic tissue reaction. Monocytes or CD34-positive myeloid progenitor cells

  8. CD43 Promotes Cells Transformation by Preventing Merlin-Mediated Contact Inhibition of Growth

    PubMed Central

    Camacho-Concha, Nohemi; Olivos-Ortiz, Amiel; Nuñez-Rivera, Alfredo; Pedroza-Saavedra, Adolfo; Gutierrez-Xicotencatl, Lourdes; Rosenstein, Yvonne; Pedraza-Alva, Gustavo

    2013-01-01

    In normal tissues, strict control of tissue size is achieved by regulating cell numbers. The mechanism that controls total cell number is known as contact inhibition of growth and it depends on the NF2/Merlin pathway. Negative regulation of this pathway by deleterious mutations or by oncogenes results in cell transformation and tumor progression. Here we provide evidence that the CD43 sialomucin cooperates with oncogenic signals to promote cell transformation by abrogating the contact inhibition of growth through a molecular mechanism that involves AKT-dependent Merlin phosphorylation and degradation. Accordingly, inhibition of endogenous CD43 expression by RNA interference in lung, cervix and colon human cancer cells impaired tumor growth in vivo. These data underscore a previously unidentified role for CD43 in non-hematopoietic tumor progression. PMID:24260485

  9. Hydroperoxide lyase products, hexanal, hexenal and nonenal, inhibit soybean seedling growth

    SciTech Connect

    Gardner, H.W.; Dornbos, D.L. Jr. (Dept. of Agriculture, Peoria, IL (USA))

    1989-04-01

    Hexanal, a product of hydroperoxide lyase, inhibited the germination and growth of soybean seeds. Hexanal was continuously delivered to germinating seeds as a vapor dissolved in air with a flow-through system (100 ml/min). Only 0.8 {mu}g hexanal/ml air was required to inhibit seedling growth by 50%; nearly 100% inhibition occurred with a dose of 1.8 {mu}g hexanal/ml air. In the absence of hexanal brown spots were often visible on the seedlings, but at sublethal doses of hexanal, the seedlings were largely devoid of these spots. The relative toxicity of three hydroperoxide lyase products, hexanal, trans-2-hexanal and trans-2-nonenal, were compared with a Petri-dish bioassay. The order of toxicity against seedling growth was hexenal>hexanal>nonenal.

  10. Antiangiogenic and proapoptotic activities of allyl isothiocyanate inhibit ascites tumor growth in vivo.

    PubMed

    Kumar, Akhilesh; D'Souza, Saritha S; Tickoo, Sanjay; Salimath, Bharathi P; Singh, H B

    2009-03-01

    The authors investigate the antiangiogenic and proapoptotic effects of mustard essential oil containing allyl isothiocyanate (AITC) and explore its mechanism of action on Ehrlich ascites tumor (EAT) cells. Swiss albino mice transplanted with EAT cells were used to study the effect of AITC. AITC was effective at a concentration of 10 mum as demonstrated by the inhibition of proliferation of EAT cells when compared with the normal HEK293 cells. It significantly reduced ascites secretion and tumor cell proliferation by about 80% and inhibited vascular endothelial growth factor expression in tumor-bearing mice in vivo. It also reduced vessel sprouting and exhibited potent antiangiogenic activity in the chorioallantoic membrane and cornea of the rat. AITC arrested the growth of EAT cells by inducing apoptosis and effectively arrested cell cycle progression at the G1 phase. The results clearly suggest that AITC inhibits tumor growth by both antiangiogenic and proapoptotic mechanisms. PMID:19223371

  11. Rhizobium-initiated rice growth inhibition caused by nitric oxide accumulation.

    PubMed

    Perrine-Walker, Francine M; Gartner, Elena; Hocart, Charles H; Becker, Anke; Rolfe, Barry G

    2007-03-01

    Isolates of Rhizobium leguminosarum bv. trifolii (the clover root-nodule endosymbiont) from the Nile River delta have been found to infect rice roots and colonize the intercellular spaces of the rice roots. Some of these isolates inhibit rice seedling growth but one in particular, R4, has been found in rice roots which develop and grow normally. We present evidence that the induced growth inhibition is due to a toxic accumulation of nitric oxide (NO), from the reduction of nitrate, and suggest that the reason that R4 does not inhibit rice root growth is because it is capable of completing the reduction of NO through to nitrogen gas. Thus, strain R4 is a candidate for engineering into a future biological nitrogen fixation system within these roots. PMID:17378431

  12. Dietary protein restriction inhibits tumor growth in human xenograft models of prostate and breast cancer

    PubMed Central

    Rastelli, Antonella L.; Miles, Kiersten Marie; Ciamporcero, Eric; Longo, Valter D.; Nguyen, Holly; Vessella, Robert; Pili, Roberto

    2013-01-01

    Purpose: Data from epidemiological and experimental studies suggest that dietary protein intake may play a role in inhibiting prostate and breast cancer by modulating the IGF/AKT/mTOR pathway. In this study we investigated the effects of diets with different protein content or quality on prostate and breast cancer. Experimental Design: To test our hypothesis we assessed the inhibitory effect of protein diet restriction on prostate and breast cancer growth, serum PSA and IGF-1 concentrations, mTOR activity and epigenetic markers, by using human xenograft cancer models. Results: Our results showed a 70% inhibition of tumor growth in the castrate-resistant LuCaP23.1 prostate cancer model and a 56% inhibition in the WHIM16 breast cancer model fed with a 7% protein diet when compared to an isocaloric 21% protein diet. Inhibition of tumor growth correlated, in the LuCaP23.1 model, with decreased serum PSA and IGF-1 levels, down-regulation of mTORC1 activity, decreased cell proliferation as indicated by Ki67 staining, and reduction in epigenetic markers of prostate cancer progression, including the histone methyltransferase EZH2 and the associated histone mark H3K27me3. In addition, we observed that modifications of dietary protein quality, independently of protein quantity, decreased tumor growth. A diet containing 20% plant protein inhibited tumor weight by 37% as compared to a 20% animal dairy protein diet. Conclusions: Our findings suggest that a reduction in dietary protein intake is highly effective in inhibiting tumor growth in human xenograft prostate and breast cancer models, possibly through the inhibition of the IGF/AKT/mTOR pathway and epigenetic modifications. PMID:24353195

  13. Monensin inhibits growth of bacterial contaminants from fuel ethanol plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contamination of commercial fermentation cultures by lactic acid bacteria (LAB) is a common and costly problem to the fuel ethanol industry. Virginiamycin (VIR) and penicillin (PEN) are frequently used to control bacterial contamination but extensive use of antibiotics may select for strains with d...

  14. The inhibition of mild steel corrosion in acidic medium by 2,2?-bis(benzimidazole)

    NASA Astrophysics Data System (ADS)

    Abboud, Y.; Abourriche, A.; Saffaj, T.; Berrada, M.; Charrouf, M.; Bennamara, A.; Cherqaoui, A.; Takky, D.

    2006-09-01

    A new corrosion inhibitor, namely 2,2'-bis(benzimidazole) has been synthesised and its inhibiting action on the corrosion of mild steel in acidic bath (1 M HCl) has been investigated by various corrosion monitoring techniques, such as corrosion weight loss test and potentiodynamic polarisation. The results of the investigation show that this compounds have fairly good inhibiting properties for steel corrosion in hydrochloric acid, and is a mixed inhibitor in (1 M HCl). The adsorption of this inhibitor is also found to obey the Langmuir adsorption isotherm.

  15. Glycyrrhizic acid inhibits apoptosis and fibrosis in carbon-tetrachloride-induced rat liver injury

    PubMed Central

    Liang, Bo; Guo, Xiao-Ling; Jin, Jing; Ma, Yong-Chun; Feng, Zheng-Quan

    2015-01-01

    AIM: To investigate anti-apoptotic effects of glycyrrhizic acid (GA) against fibrosis in carbon tetrachloride (CCl4)-induced liver injury and its contributing factors. METHODS: Liver fibrosis was induced by administration of CCl4 for 8 wk. Pathological changes in the liver of rats were examined by hematoxylin-eosin staining. Collagen fibers were detected by Sirius red staining. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of cleaved caspase-3, Bax, ?-SMA, connective tissue growth factor (CTGF), matrix metalloproteinase (MMP) 2 and MMP9 proteins were evaluated by western blot analysis, and ?-SMA mRNA, collagen type?I?and III mRNA were estimated by real-time PCR. RESULTS: Treatment with GA significantly improved the pathological changes in the liver and markedly decreased the positive area of Sirius red compared with rats in the CCl4-treated group. TUNEL assay showed that GA significantly reduced the number of TUNEL-positive cells compared with the CCl4-treated group. The expression levels of cleaved caspase-3, Bax, ?-SMA, CTGF, MMP2 and MMP9 proteins, and ?-SMA mRNA, collagen type?I?and III mRNA were also significantly reduced by GA compared with the CCl4-treated group (P < 0.05). CONCLUSION: GA treatment can ameliorate CCl4-induced liver fibrosis by inhibiting hepatocyte apoptosis and hepatic stellate cell activation. PMID:25954100

  16. TRANSPARENT TESTA8 Inhibits Seed Fatty Acid Accumulation by Targeting Several Seed Development Regulators in Arabidopsis.

    PubMed

    Chen, Mingxun; Xuan, Lijie; Wang, Zhong; Zhou, Longhua; Li, Zhilan; Du, Xue; Ali, Essa; Zhang, Guoping; Jiang, Lixi

    2014-04-10

    Fatty acids (FAs) and FA-derived complex lipids play important roles in plant growth and vegetative development and are a class of prominent metabolites stored in mature seeds. The factors and regulatory networks that control FA accumulation in plant seeds remain largely unknown. The role of TRANSPARENT TESTA8 (TT8) in the regulation of flavonoid biosynthesis and the formation of seed coat color is extensively studied; however, its function in affecting seed FA biosynthesis is poorly understood. In this article, we show that Arabidopsis (Arabidopsis thaliana) TT8 acts maternally to affect seed FA biosynthesis and inhibits seed FA accumulation by down-regulating a group of genes either critical to embryonic development or important in the FA biosynthesis pathway. Moreover, the tt8 mutation resulted in reduced deposition of protein in seeds during maturation. Posttranslational activation of a TT8-GLUCOCORTICOID RECEPTOR fusion protein and chromatin immunoprecipitation assays demonstrated that TT8 represses the activities of LEAFY COTYLEDON1, LEAFY COTYLEDON2, and FUSCA3, the critical transcriptional factors important for seed development, as well as CYTIDINEDIPHOSPHATE DIACYLGLYCEROL SYNTHASE2, which mediates glycerolipid biosynthesis. These results help us to understand the entire function of TT8 and increase our knowledge of the complicated networks regulating the formation of FA-derived complex lipids in plant seeds. PMID:24722549

  17. Caffeic acid phenethyl ester (CAPE), an active component of propolis, inhibits Helicobacter pylori peptide deformylase activity.

    PubMed

    Cui, Kunqiang; Lu, Weiqiang; Zhu, Lili; Shen, Xu; Huang, Jin

    2013-05-31

    Helicobacter pylori (H. pylori) is a major causative factor for gastrointestinal illnesses, H. pylori peptide deformylase (HpPDF) catalyzes the removal of formyl group from the N-terminus of nascent polypeptide chains, which is essential for H. pylori survival and is considered as a promising drug target for anti-H. pylori therapy. Propolis, a natural antibiotic from honeybees, is reported to have an inhibitory effect on the growth of H. pylori in vitro. In addition, previous studies suggest that the main active constituents in the propolis are phenolic compounds. Therefore, we evaluated a collection of phenolic compounds derived from propolis for enzyme inhibition against HpPDF. Our study results show that Caffeic acid phenethyl ester (CAPE), one of the main medicinal components of propolis, is a competitive inhibitor against HpPDF, with an IC50 value of 4.02 ?M. Furthermore, absorption spectra and crystal structural characterization revealed that different from most well known PDF inhibitors, CAPE block the substrate entrance, preventing substrate from approaching the active site, but CAPE does not have chelate interaction with HpPDF and does not disrupt the metal-dependent catalysis. Our study provides valuable information for understanding the potential anti-H. pylori mechanism of propolis, and CAPE could be served as a lead compound for further anti-H. pylori drug discovery. PMID:23611786

  18. The secreted glycoprotein CREG inhibits cell growth dependent on the mannose-6-phosphate/insulin-like growth factor II receptor.

    PubMed

    Di Bacco, Alessandra; Gill, Grace

    2003-08-21

    Secreted proteins and their cognate receptors are implicated in a myriad of activities that regulate cell proliferation, differentiation, and development. CREG, a cellular repressor of E1A-stimulated genes, is a secreted glycoprotein that antagonizes cellular transformation by E1A and ras. We have previously shown that CREG expression is induced very early during differentiation of pluripotent cells and, even in the absence of other inducers, CREG promotes neuronal differentiation of human teratocarcinoma NTERA-2 cells. Here we show that ectopic expression of CREG in NTERA-2 cells results in a delay of the G1/S phase transition of the cell cycle and growth inhibition. We show that CREG binds directly to the mannose-6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) dependent on CREG glycosylation. The M6P/IGF2R is a tumor suppressor that functions to control cell growth through interactions with multiple ligands. By analysing CREG activity in cells lacking M6P/IGF2R expression, we show that this receptor is required for CREG-induced growth inhibition. These studies reveal that CREG inhibits cell growth dependent on the M6P/IGF2R and suggest that interactions between CREG and a well-characterized tumor suppressor may contribute to regulation of proliferation and differentiation in multiple lineages. PMID:12934103

  19. Inhibition of growth by calcitriol in a proximal tubular cell line (OK).

    PubMed

    Weih, M; Orth, S; Weinreich, T; Reichel, H; Ritz, E

    1994-01-01

    Calcitriol has been shown to inhibit (i) cell proliferation of renal carcinoma cell lines and of cultured adult human mesangial cells in vitro, and (ii) renal compensatory growth in vivo. In the present study we examined the effects of calcitriol on DNA synthesis and cell replication in an immortalized cell line showing the phenotypic characteristics of proximal tubular cells (opossum kidney, OK cells). The viability of OK cells was not affected by calcitriol (Trypan-blue exclusion, LDH and K+ release), but the cells did not convert 3H-25(OH)2D3 to 3H-1,25(OH)2D3. In the log growth phase, calcitriol (but not alternative vitamin D metabolites) caused dose-dependent (10(-12) to 10(-6) M) inhibition of radiothymidine incorporation. Inhibition was calcium dependent, i.e. it was more pronounced at the lower nominal calcium concentration in tissue culture media (0.9 versus 1.8 mmol/l) and amplified by coincubation with nifedipine (1 microM). Inhibition of DNA synthesis was paralleled by inhibition of cell replication (growth curve) under basal conditions and after stimulation with EGF (10 ng/ml). In conclusion, calcitriol inhibits proliferation of proximal tubular cells which normally express 1-alpha-hydroxylase activity. PMID:7816250

  20. Inhibition of Tumor Growth by Dietary Zinc Deficiency1

    Microsoft Academic Search

    James T. McQuitty; William D. DeWys; Liberatore Monaco; William H. Strain; Charles G. Rob; Jean Apgar; Walter J. Pories

    SUMMARY The effect of different levels of zinc intake on tumor growth was studied by implanting Walker 256 carcino- sarcoma into weanling Sprague-Dawley rats maintained on laboratory chow or on a zinc-deficient synthetic diet. Three experimental groups receiving this synthetic diet were given 0, 50, or 500 parts per million, respectively, of zinc ion in the drinking water. The latter

  1. Vascular endothelial growth factor inhibition in uveitis: a systematic review

    Microsoft Academic Search

    Nishi Gulati; Farzin Forooghian; Ronni Lieberman; Douglas A Jabs

    2010-01-01

    Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of uveitic complications such as cystoid macular oedema (CMO), choroidal neovasularisation (CNV) and retinal neovascularisation (RNV). The use of intravitreal anti-VEGF therapies, namely bevacizumab and ranibizumab, has recently been described in the treatment of these complications. Evidence describing the use of intravitreal anti-VEGF therapy for these complications consists

  2. Di (2-ethylhexyl) phthalate inhibits growth of ovarian antral follicles through an oxidative stress pathway

    PubMed Central

    Wang, Wei; Craig, Zelieann R.; Basavarajappa, Mallikarjuna S.; Gupta, Rupesh; Flaws, Jodi A.

    2011-01-01

    Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 32–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100?g/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1mM). During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10?g/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. PMID:22155089

  3. Inhibition of Lymphoid Tyrosine Phosphatase by Benzofuran Salicylic Acids

    PubMed Central

    Vang, Torkel; Xie, Yuli; Liu, Wallace H.; Vidovi?, Dušica; Liu, Yidong; Wu, Shuangding; Smith, Deborah H.; Rinderspacher, Alison; Chung, Caty; Gong, Gangli; Mustelin, Tomas; Landry, Donald W.; Rickert, Robert C.; Schürer, Stephan C.; Deng, Shi-Xian; Tautz, Lutz

    2011-01-01

    The lymphoid tyrosine phosphatase (Lyp, PTPN22) is a critical negative regulator of T cell antigen receptor (TCR) signaling. A single-nucleotide polymorphism (SNP) in the ptpn22 gene correlates with the incidence of various autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Since the disease-associated allele is a more potent inhibitor of TCR signaling, specific Lyp inhibitors may become valuable in treating autoimmunity. Using a structure-based approach, we synthesized a library of 34 compounds that inhibited Lyp with IC50 values between 0.27 and 6.2 ?M. A reporter assay was employed to screen for compounds that enhanced TCR signaling in cells, and several inhibitors displayed a dose-dependent, activating effect. Subsequent probing for Lyp's direct physiological targets by immunoblot analysis confirmed the ability of the compounds to inhibit Lyp in T cells. Selectivity profiling against closely related tyrosine phosphatases and in silico docking studies with the crystal structure of Lyp yielded valuable information for the design of Lyp-specific compounds. PMID:21190368

  4. Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine inhibit fungal growth.

    PubMed Central

    Kerr, J R; Taylor, G W; Rutman, A; Høiby, N; Cole, P J; Wilson, R

    1999-01-01

    AIM: To examine strains of Pseudomonas aeruginosa for specific antifungal factors. METHODS: Two clinical strains of P aeruginosa with strong in vitro inhibition (by cross streak assay) of Candida albicans and Aspergillus fumigatus were examined. Both strains were isolated from sputum--one from a patient with cystic fibrosis and one from a patient with bronchiectasis. Bacterial extracts were fractionated by high performance liquid chromatography and examined by ultraviolet absorbance and mass spectroscopy. Antifungal activity against C albicans and A fumigatus was determined in a well plate assay. RESULTS: Pyocyanin was the major antifungal agent of P aeruginosa; 1-hydroxy-phenazine also possessed activity. Pyocyanin MICs for C albicans and A fumigatus were > 64 micrograms/ml. These phenazines were active against nine other yeast species pathogenic for man. Preliminary experiments also suggested possible inhibition of yeast mycelial transformation in C albicans by pyocyanin. CONCLUSIONS: There may be a role for pyocyanin and 1-hydroxyphenazine in the prevention of pulmonary candidiasis in patients colonised by P aeruginosa. PMID:10560362

  5. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids

    PubMed Central

    Kamphorst, Jurre J.; Cross, Justin R.; Fan, Jing; de Stanchina, Elisa; Mathew, Robin; White, Eileen P.; Thompson, Craig B.; Rabinowitz, Joshua D.

    2013-01-01

    Cancer cell growth requires fatty acids to replicate cellular membranes. The kinase Akt is known to up-regulate fatty acid synthesis and desaturation, which is carried out by the oxygen-consuming enzyme stearoyl-CoA desaturase (SCD)1. We used 13C tracers and lipidomics to probe fatty acid metabolism, including desaturation, as a function of oncogene expression and oxygen availability. During hypoxia, flux from glucose to acetyl-CoA decreases, and the fractional contribution of glutamine to fatty acid synthesis increases. In addition, we find that hypoxic cells bypass de novo lipogenesis, and thus, both the need for acetyl-CoA and the oxygen-dependent SCD1-reaction, by scavenging serum fatty acids. The preferred substrates for scavenging are phospholipids with one fatty acid tail (lysophospholipids). Hypoxic reprogramming of de novo lipogenesis can be reproduced in normoxic cells by Ras activation. This renders Ras-driven cells, both in culture and in allografts, resistant to SCD1 inhibition. Thus, a mechanism by which oncogenic Ras confers metabolic robustness is through lipid scavenging. PMID:23671091

  6. Inhibition of Hsp27 Radiosensitizes Head-and-Neck Cancer by Modulating Deoxyribonucleic Acid Repair

    SciTech Connect

    Guttmann, David M.; Hart, Lori [Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Du, Kevin [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States); Seletsky, Andrew [Department of Biology, Drexel University, Philadelphia, Pennsylvania (United States); Koumenis, Constantinos, E-mail: koumenis@xrt.upenn.edu [Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2013-09-01

    Purpose: To present a novel method of tumor radiosensitization through Hsp27 knockdown using locked nucleic acid (LNA) and to investigate the role of Hsp27 in DNA double strand break (DSB) repair. Methods and Materials: Clonogenic survival assays, immunoblotting, the proximity ligation assay, and ?H2AX foci analysis were conducted in SQ20B and FaDu human head-and-neck cancer cell lines treated with Hsp27 LNA and Hsp27 short hairpin RNA (shRNA). Additionally, nude mice with FaDu flank tumors were treated with fractionated radiation therapy after pretreatment with Hsp27 LNA and monitored for tumor growth. Results: Hsp27 LNA and Hsp27 shRNA radiosensitized head-and-neck cancer cell lines in an Hsp27-dependent manner. Ataxia-Telangectasia Mutated-mediated DNA repair signaling was impaired in irradiated cells with Hsp27 knockdown. ATM kinase inhibition abrogated the radiosensitizing effect of Hsp27. Furthermore, Hsp27 LNA and shRNA both attenuated DNA repair kinetics after radiation, and Hsp27 was found to colocalize with ATM in both untreated and irradiated cells. Last, combined radiation and Hsp27 LNA treatment in tumor xenografts in nude mice suppressed tumor growth compared with either treatment alone. Conclusions: These results support a radiosensitizing property of Hsp27 LNA in vitro and in vivo, implicate Hsp27 in double strand break repair, and suggest that Hsp27 LNA might eventually serve as an effective clinical agent in the radiotherapy of head-and-neck cancer.

  7. OVA12, a novel tumor antigen, promotes cancer cell growth and inhibits 5-fluorouracil-induced apoptosis.

    PubMed

    Zhang, Renfeng; Jin, Shu; Rao, Wei; Song, Feifei; Yin, Qinqin; Wang, Ying; Wang, Li; Xi, Yebin; Zhang, Xiaoren; Wang, Mingliang; Ge, Hailiang

    2015-02-01

    To achieve a better understanding of mechanisms that underlie carcinogenesis and to identify novel target molecules for diagnosis and therapy of carcinoma, we previously identified 24 distinct gene clones by immunoscreening of a cDNA library derived from an ovarian cancer patient through SEREX analysis. Among these genes we focused on a novel gene termed OVA12 and which putatively encodes a 114-amino-acid protein. In the present study, we found that OVA12 was ubiquitously overexpressed in diverse human tumor cell lines. Interestingly, we noticed that overexpression of OVA12 promoted proliferation of cancer cells in vitro and accelerated tumor growth in nude mice as compared to controls. Conversely, specific downregulation of OVA12 inhibited tumor cell proliferation and tumor growth both in vitro and in vivo. Furthermore, OVA12 inhibited 5-FU-induced apoptosis through specific upregulation of Mcl-1 and survivin. These results demonstrate that OVA12 is able to promote tumor growth, suggesting that this antigen might be a new potential target for development of cancer therapy. PMID:25444895

  8. Inhibition by loperamide of deoxycholic acid induced intestinal secretion

    Microsoft Academic Search

    U. M. Farack; K. Loeschke

    1984-01-01

    The effect of loperamide on deoxycholic acid (DOC)-induced secretion was studied in ligated loops of the rat jejunum and colon in vivo. In controls loperamide slightly augmented fluid absorption. 3 mmol DOC caused net fluid secretion. Loperamide reduced this secretion in the colon and reversed it to absorption in the jejunum. Na-K-ATPase specific activity and cAMP levels were measured in

  9. Inhibition of a DNA-helicase by peptide nucleic acids

    Microsoft Academic Search

    Lionel Bastide; Paul E. Boehmer; Giuseppe Villani; Bernard Lebleu

    1999-01-01

    Bis-peptide nucleic acid (bis-PNA) binding results in D-loop formation by strand displacement at comple- mentary homopurine stretches in DNA duplexes. Transcription and replication in intact cells is mediated by multienzymatic complexes involving several proteins other than polymerases. The behaviour of the highly stable clamp structure formed by bis-PNAs has thus far been studied with respect to their capacity to arrest

  10. Inhibiting transcription of chromosomal DNA with antigene peptide nucleic acids

    Microsoft Academic Search

    Bethany A Janowski; Kunihiro Kaihatsu; Kenneth E Huffman; Jacob C Schwartz; Rosalyn Ram; Daniel Hardy; Carole R Mendelson; David R Corey

    2005-01-01

    Synthetic molecules that recognize specific sequences within cellular DNA are potentially powerful tools for investigating chromosome structure and function. Here, we designed antigene peptide nucleic acids (agPNAs) to target the transcriptional start sites for the human progesterone receptor B (hPR-B) and A (hPR-A) isoforms at sequences predicted to be single-stranded within the open complex of chromosomal DNA. We found that

  11. Oleic acid and linoleic acid from Tenebrio molitor larvae inhibit BACE1 activity in vitro: molecular docking studies.

    PubMed

    Youn, Kumju; Yun, Eun-Young; Lee, Jinhyuk; Kim, Ji-Young; Hwang, Jae-Sam; Jeong, Woo-Sik; Jun, Mira

    2014-02-01

    In our ongoing research to find therapeutic compounds for Alzheimer's disease (AD) from natural resources, the inhibitory activity of the BACE1 enzyme by Tenebrio molitor larvae and its major compounds were evaluated. The T. molitor larvae extract and its fractions exhibited strong BACE1 suppression. The major components of hexane fraction possessing both high yield and strong BACE1 inhibition were determined by thin layer chromatography, gas chromatography, and nuclear magnetic resonance analysis. A remarkable composition of unsaturated long chain fatty acids, including oleic acid and linoleic acid, were identified. Oleic acid, in particular, noncompetitively attenuated BACE1 activity with a half-maximal inhibitory concentration (IC??) value of 61.31 ?M and Ki value of 34.3??M. Furthermore, the fatty acids were stably interacted with BACE1 at different allosteric sites of the enzyme bound with the OH of CYS319 and the NH? of TYR320 for oleic acid and with the C=O group of GLN304 for linoleic acid. Here, we first revealed novel pharmacophore features of oleic acids and linoleic acid to BACE1 by in silico docking studies. The present findings would clearly suggest potential guidelines for designing novel BACE1 selective inhibitors. PMID:24548007

  12. Inhibition of tubulin polymerization by hypochlorous acid and chloramines.

    PubMed

    Landino, Lisa M; Hagedorn, Tara D; Kim, Shannon B; Hogan, Katherine M

    2011-04-15

    Protein thiol oxidation and modification by nitric oxide and glutathione are emerging as common mechanisms to regulate protein function and to modify protein structure. Also, thiol oxidation is a probable outcome of cellular oxidative stress and is linked to degenerative disease progression. We assessed the effect of the oxidants hypochlorous acid and chloramines on the cytoskeletal protein tubulin. Total cysteine oxidation by the oxidants was monitored by labeling tubulin with the thiol-selective reagent 5-iodoacetamidofluorescein; by reaction with Ellman's reagent, 5,5'-dithiobis(2-nitrobenzoic acid); and by detecting interchain tubulin disulfides by Western blot under nonreducing conditions. Whereas HOCl induced both cysteine and methionine oxidation of tubulin, chloramines were predominantly cysteine oxidants. Cysteine oxidation of tubulin, rather than methionine oxidation, was associated with loss of microtubule polymerization activity, and treatment of oxidized tubulin with disulfide reducing agents restored a considerable portion of the polymerization activity that was lost after oxidation. By comparing the reactivity of hypochlorous acid and chloramines with the previously characterized oxidants, peroxynitrite and the nitroxyl donor Angeli's salt, we have identified tubulin thiol oxidation, not methionine oxidation or tyrosine nitration, as a common outcome responsible for decreased polymerization activity. PMID:21256958

  13. Phytohaemagglutinin inhibits gastric acid but not pepsin secretion in conscious rats.

    PubMed

    Kordás, K; Szalmay, G; Bardocz, S; Pusztai, A; Varga, G

    2001-01-01

    Phytohaemagglutinin (PHA), a kidney bean lectin, is known for its binding capability to the small intestinal surface. There has been no data available, however, on the biological activity of PHA in the stomach. Recent observations indicate that PHA is able to attach to gastric mucosal and parietal cells. Therefore, we examined whether PHA affects gastric acid and pepsin secretion in rats. Rats were surgically prepared with chronic stainless steel gastric cannula and with indwelling polyethylene jugular vein catheter. During experiments, animals were slightly restrained. Gastric acid secretion was collected in 30 min periods. Acid secretion was determined by titration of the collected gastric juice with 0.02 N NaOH to pH 7.0. Pepsin activity was estimated by measuring enzymatic activity. Saline, pentagastrin and histamine were infused intravenously. PHA or bovine serum albumin (BSA) were dissolved in saline and given intragastrically through the gastric cannula. PHA significantly inhibited basal acid secretion. Inhibition of acid output reached 72% during the first collection period following PHA administration when compared, then gradually disappeared. Pentagastrin-stimulated acid secretion was repressed dose-dependently by PHA as well. Maximal inhibition was observed during the first 30 min following application of PHA. Histamine-stimulated acid secretion was inhibited by PHA in a similar manner. Pepsin secretion was not affected by PHA under either basal or stimulated conditions. These results provide evidence that PHA is a potent inhibitor of gastric acid secretion in conscious rats, but it does not affect pepsin output from the stomach. PMID:11595455

  14. Tannic Acid Inhibits Hepatitis C Virus Entry into Huh7.5 Cells

    PubMed Central

    Hagedorn, Curt H.

    2015-01-01

    Chronic infection with the hepatitis C virus (HCV) is a cause of cirrhosis and hepatocellular carcinoma worldwide. Although antiviral therapy has dramatically improved recently, a number of patients remain untreated and some do not clear infection with treatment. Viral entry is an essential step in initiating and maintaining chronic HCV infections. One dramatic example of this is the nearly 100% infection of newly transplanted livers in patients with chronic hepatitis C. HCV entry inhibitors could play a critical role in preventing HCV infection of newly transplanted livers. Tannic acid, a polymer of gallic acid and glucose molecules, is a plant-derived polyphenol that defends some plants from insects and microbial infections. It has been shown to have a variety of biological effects, including antiviral activity, and is used as a flavoring agent in foods and beverages. In this study, we demonstrate that tannic acid is a potent inhibitor of HCV entry into Huh7.5 cells at low concentrations (IC50 5.8 ?M). It also blocks cell-to-cell spread in infectious HCV cell cultures, but does not inhibit HCV replication following infection. Moreover, experimental results indicate that tannic acid inhibits an early step of viral entry, such as the docking of HCV at the cell surface. Gallic acid, tannic acid’s structural component, did not show any anti-HCV activity including inhibition of HCV entry or replication at concentrations up to 25 ?M. It is possible the tannin structure is related on the effect on HCV inhibition. Tannic acid, which is widely distributed in plants and foods, has HCV antiviral activity in cell culture at low micromolar concentrations, may provide a relative inexpensive adjuvant to direct-acting HCV antivirals and warrants future investigation. PMID:26186636

  15. Inhibition of pancreatic carboxypeptidase A: A possible mechanism of interaction between penicillic acid and ochratoxin A

    Microsoft Academic Search

    Roger W. Parker; Timothy D. Phillips; Leon F. Kubena; Leon H. Russell; Norman D. Heidelbaugh

    1982-01-01

    Penicillic acid and ochratoxin A are environmentally important toxic fungal metabolites (mycotoxins) that are synergistic in combination. The effects of penicillic acid on the pancreatic enzyme, :arboxypeptidase A were investigated in vitro and in vivo. A broad range of inhibition in vitro of the enzyme by PA was demonstrated with a half?maximal inhibitory concentration equal to 1.1 x 10M PA.

  16. Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9

    PubMed Central

    Omanakuttan, Athira; Nambiar, Jyotsna; Harris, Rodney M.; Bose, Chinchu; Pandurangan, Nanjan; Varghese, Rebu K.; Kumar, Geetha B.; Tainer, John A.; Banerji, Asoke; Perry, J. Jefferson P.

    2012-01-01

    Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1? pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dose-dependent manner, with an IC50 of 11.11 ?M. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action. PMID:22745359

  17. Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases.

    PubMed

    Aoyama, Yumi; Avruch, Joseph; Zhang, Xian-Feng

    2004-04-22

    Nore1, a noncatalytic protein identified by its ability to bind selectively to active Ras, is most closely related in amino-acid sequence to the tumor suppressor RASSF1. Both are expressed predominantly as a longer (Nore1A/RASSF1A) and/or shorter (Nore1B/RASSF1C) polypeptide; all four polypeptides contain a Ras-association domain and bind, through their conserved carboxytermini, the proapoptotic protein kinases MST1 and MST2. Moreover, the expression of the longer polypeptide is downregulated in human tumor cell lines through promoter methylation (frequently for RASSF1A, less regularly for Nore1A). Forced expression of RASSF1A in several such lines (including the NSCLC line A549) has been shown to suppress tumorigenicity; herein we inquire whether Nore has growth inhibitory activity. Four tumor cell lines were tested, selected for their low expression of both Nore1A and Nore1B; the two NSCLC lines, A549 and NCI-H460, each have a mutant active Ras oncogene, whereas the two melanoma lines G361 and M14 each contain the constitutively active BRaf(V599E) oncogene and wild-type Ras. The expression of Nore1A or Nore1B suppresses colony formation by the A549 and G361 lines, as effectively in A549 as does RASSF1A; colony formation in the NCI-H460 and M14 lines is unaffected. Nore1A inhibits anchorage-independent growth by A549 cells and delays A549 progression through G1 without evidence of increased apoptosis. The growth suppressive action of Nore1A is largely unaffected by deletion of both the MST- and Ras-binding domains, as well as by mutation of the Nore1A zinc finger. Thus, Nore1 suppresses the growth of some tumor cell lines through as yet unidentified effectors, independent of Ras-like proteins or MST1/2. PMID:15007383

  18. Longan Flower Extract Inhibits the Growth of Colorectal Carcinoma

    Microsoft Academic Search

    Chih-Ping Hsu; Ying-Hsi Lin; Shi-Ping Zhou; Yuan-Chiang Chung; Chih-Cheng Lin; Shao-Cheng Wang

    2010-01-01

    Longan flower extract (LFE) has been shown to exhibit free radical scavenging ability and anti-inflammatory effects. However, the effect of LFE treatment on the growth of colorectal cancer cells has not been evaluated. This study investigated the effect of LFE on two colorectal cancer cell lines, SW-480 and Colo 320DM, and the possible mechanisms involved. LFE-treated cells were assessed for

  19. Embryo growth, testa permeability, and endosperm weakening are major targets for the environmentally regulated inhibition of Lepidium sativum seed germination by myrigalone A.

    PubMed

    Voegele, Antje; Graeber, Kai; Oracz, Krystyna; Tarkowská, Danuše; Jacquemoud, Dominique; Ture?ková, Veronika; Urbanová, Terezie; Strnad, Miroslav; Leubner-Metzger, Gerhard

    2012-09-01

    Myrigalone A (MyA) is a rare flavonoid in fruit leachates of Myrica gale, a deciduous shrub adapted to flood-prone habitats. As a putative allelochemical it inhibits seed germination and seedling growth. Using Lepidium sativum as a model target species, experiments were conducted to investigate how environmental cues modulate MyA's interference with key processes of seed germination. Time course analyses of L. sativum testa and endosperm rupture under different light conditions and water potentials were combined with quantifying testa permeability, endosperm weakening, tissue-specific gibberellin (GA) and abscisic acid (ABA) contents, as well as embryo growth and apoplastic superoxide production important for cell expansion growth. Lepidium sativum testa permeability and early water uptake by imbibition is enhanced by MyA. During late germination, MyA inhibits endosperm weakening and embryo growth, both processes required for endosperm rupture. Inhibition of embryo cell expansion by MyA depends on environmental cues, which is evident from the light-modulated severity of the MyA-mediated inhibition of apoplastic superoxide accumulation. Several important key weakening and growth processes during early and late germination are targets for MyA. These effects are modulated by light conditions and ambient water potential. It is speculated that MyA is a soil seed bank-destroying allelochemical that secures the persistence of M. gale in its flood-prone environment. PMID:22821938

  20. Embryo growth, testa permeability, and endosperm weakening are major targets for the environmentally regulated inhibition of Lepidium sativum seed germination by myrigalone A

    PubMed Central

    2012-01-01

    Myrigalone A (MyA) is a rare flavonoid in fruit leachates of Myrica gale, a deciduous shrub adapted to flood-prone habitats. As a putative allelochemical it inhibits seed germination and seedling growth. Using Lepidium sativum as a model target species, experiments were conducted to investigate how environmental cues modulate MyA’s interference with key processes of seed germination. Time course analyses of L. sativum testa and endosperm rupture under different light conditions and water potentials were combined with quantifying testa permeability, endosperm weakening, tissue-specific gibberellin (GA) and abscisic acid (ABA) contents, as well as embryo growth and apoplastic superoxide production important for cell expansion growth. Lepidium sativum testa permeability and early water uptake by imbibition is enhanced by MyA. During late germination, MyA inhibits endosperm weakening and embryo growth, both processes required for endosperm rupture. Inhibition of embryo cell expansion by MyA depends on environmental cues, which is evident from the light-modulated severity of the MyA-mediated inhibition of apoplastic superoxide accumulation. Several important key weakening and growth processes during early and late germination are targets for MyA. These effects are modulated by light conditions and ambient water potential. It is speculated that MyA is a soil seed bank-destroying allelochemical that secures the persistence of M. gale in its flood-prone environment. PMID:22821938

  1. Differential inhibition of nerve growth factor and epidermal growth factor effects on the PC12 pheochromocytoma line

    PubMed Central

    1984-01-01

    Tests have been made of the action of the methyltransferase inhibitors 5'-S-methyl adenosine, 5'-S-(2-methyl-propyl)-adenosine, and 3-deaza- adenosine +/- L-homocysteine thiolactone, on nerve growth factor (NGF)- dependent events in the rat pheochromocytoma line PC12. Each of these agents inhibited NGF-dependent neurite outgrowth at concentrations of the order of millimolar. Slow initiation of neurite outgrowth over several days and more rapid regeneration of neurites (congruent to 1 d) were blocked, as was the priming mechanism necessary for genesis of neurites. The inhibitions were reversible in that PC12 cells maintained for several days in the presence of inhibitors grew neurites normally after washout of these agents. Other NGF-dependent responses of the PC12 line (i.e., induction of ornithine decarboxylase activity [over 4 h], enhancement of tyrosine hydroxylase phosphorylation [over 1 h], and rapid changes in cell surface morphology [30 s onward]) were inhibited by each of the agents. In contrast, corresponding epidermal growth factor-dependent responses in ornithine decarboxylase activity, phosphorylation, and cell surface morphology were not blocked, but instead either unaffected or enhanced, by the methylation inhibitors. These inhibitors did not act by blockade of binding of NGF to high- or low-affinity cell surface receptors, though they partially inhibited internalization of [125I]NGF. The inhibition of rapidly-induced NGF- dependent events and the differential inhibition of responses to NGF and epidermal growth factor imply that the methyltransferase inhibitors specifically block one of the first steps in the mechanistic pathway for NGF. PMID:6319427

  2. Lobaplatin inhibits growth of gastric cancer cells by inducing apoptosis

    PubMed Central

    Yin, Chu-Yang; Lin, Xiao-Lin; Tian, Lei; Ye, Ming; Yang, Xin-Ying; Xiao, Xiu-Ying

    2014-01-01

    AIM: To assess the anti-cancer effect of lobaplatin on human gastric cancer cells, and to explore the underlying molecular mechanisms. METHODS: The human gastric cancer cell lines MKN-28, AGS and MKN-45 were used. The cytotoxicity of lobaplatin was detected using an MTS cell proliferation assay. Flow cytometry was used to detect cell apoptosis using Annexin V-FITC Apoptosis Detection Kit. The expression of apoptosis-regulated genes was examined at the protein level using Western blot. RESULTS: Lobaplatin inhibited the proliferation of human gastric cancer cells and induced apoptosis, which may be associated with the up-regulation of Bax expression, poly(ADP-ribose) polymerase (PARP) cleavage, p53 expression and the reduction of Bcl-2 expression. CONCLUSION: The cytotoxicity of lobaplatin may be due to its ability of inducing apoptosis of gastric cancer cells, which would support the potential use of lobaplatin for the therapy of gastric cancer. PMID:25516654

  3. Hematein, a casein kinase II inhibitor, inhibits lung cancer tumor growth in a murine xenograft model

    PubMed Central

    HUNG, MING-SZU; XU, ZHIDONG; CHEN, YU; SMITH, EMMANUEL; MAO, JIAN-HUA; HSIEH, DAVID; LIN, YU-CHING; YANG, CHENG-TA; JABLONS, DAVID M.; YOU, LIANG

    2013-01-01

    Casein kinase II (CK2) inhibitors suppress cancer cell growth. In this study, we examined the inhibitory effects of a novel CK2 inhibitor, hematein, on tumor growth in a murine xenograft model. We found that in lung cancer cells, hematein inhibited cancer cell growth, Akt/PKB Ser129 phosphorylation, the Wnt/TCF pathway and increased apoptosis. In a murine xenograft model of lung cancer, hematein inhibited tumor growth without significant toxicity to the mice tested. Molecular docking showed that hematein binds to CK2? in durable binding sites. Collectively, our results suggest that hematein is an allosteric inhibitor of protein kinase CK2 and has antitumor activity to lung cancer. PMID:24008396

  4. Inhibition of prostaglandin D? production by trihydroxy fatty acids isolated from Ulmus davidiana var. japonica.

    PubMed

    Choi, Hyun Gyu; Park, Yu Mi; Lu, Yue; Chang, Hyeun Wook; Na, Minkyun; Lee, Seung Ho

    2013-09-01

    The stem and root barks of Ulmus davidiana var. japonica (Ulmaceae) have been used to treat inflammatory diseases including mastitis, rhinitis, sinusitis, and enteritis. In an ongoing study focused on the discovery of natural anti-inflammatory compounds from natural products, a methanol extract of the stem and root barks of U. davidiana var. japonica showed anti-inflammatory activities. Activity-guided fractionation of the methanol extract yielded a new trihydroxy fatty acid, 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid (1), and a known compound, pinellic acid (2). These two trihydroxy fatty acids 1 and 2 inhibited prostaglandin D? production with IC?? values of 25.8 and 40.8??M, respectively. These results suggest that 9,12,13-trihydroxyoctadeca-10(Z),15(Z)-dienoic acid (1) and pinellic acid (2) are among the anti-inflammatory principles in this medicinal plant. PMID:23147809

  5. Midazolam Induces Cellular Apoptosis in Human Cancer Cells and Inhibits Tumor Growth in Xenograft Mice

    PubMed Central

    Mishra, Siddhartha Kumar; Kang, Ju-Hee; Lee, Chang Woo; Oh, Seung Hyun; Ryu, Jun Sun; Bae, Yun Soo; Kim, Hwan Mook

    2013-01-01

    Midazolam is a widely used anesthetic of the benzodiazepine class that has shown cytotoxicity and apoptosis-inducing activity in neuronal cells and lymphocytes. This study aims to evaluate the effect of midazolam on growth of K562 human leukemia cells and HT29 colon cancer cells. The in vivo effect of midazolam was investigated in BALB/c-nu mice bearing K562 and HT29 cells human tumor xenografts. The results show that midazolam decreased the viability of K562 and HT29 cells by inducing apoptosis and S phase cell-cycle arrest in a concentration-dependent manner. Midazolam activated caspase-9, capspase-3 and PARP indicating induction of the mitochondrial intrinsic pathway of apoptosis. Midazolam lowered mitochondrial membrane potential and increased apoptotic DNA fragmentation. Midazolam showed reactive oxygen species (ROS) scavenging activity through inhibition of NADPH oxidase 2 (Nox2) enzyme activity in K562 cells. Midazolam caused inhibition of pERK1/2 signaling which led to inhibition of the anti-apoptotic proteins Bcl-XL and XIAP and phosphorylation activation of the pro-apoptotic protein Bid. Midazolam inhibited growth of HT29 tumors in xenograft mice. Collectively our results demonstrate that midazolam caused growth inhibition of cancer cells via activation of the mitochondrial intrinsic pathway of apoptosis and inhibited HT29 tumor growth in xenograft mice. The mechanism underlying these effects of midazolam might be suppression of ROS production leading to modulation of apoptosis and growth regulatory proteins. These findings present possible clinical implications of midazolam as an anesthetic to relieve pain during in vivo anticancer drug delivery and to enhance anticancer efficacy through its ROS-scavenging and pro-apoptotic properties. PMID:24008365

  6. Microcalorimetric study of Escherichia coli aerobic growth: theoretical aspects of growth on succinic acid.

    PubMed Central

    Dermoun, Z; Belaich, J P

    1980-01-01

    Two methods of investigation were used to evaluate the heat quantity associated with anabolic processes (qan) during the aerobic growth of Escherichia coli in a minimal medium containing succinic acid as the sole energy and carbon source. The study of the contribution of biosynthetic reactions from succinic acid and ammonia were investigated by both methods. The two qan values obtained were in excellent agreement and were found to be significant. Thus it was demonstrated that the contribution of anabolism strongly influenced the quantity of heat associated with microbial aerobic growth. The qan calculated as above explained the experimental enthalpy change which was recently reported. PMID:7009563

  7. Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the xc? cystine transporter: a new action for an old drug

    Microsoft Academic Search

    PW Gout; AR Buckley; CR Simms; N Bruchovsky

    2001-01-01

    Although cyst(e)ine is nutritionally a non-essential amino acid, lymphoid cells cannot synthesize it, rendering their growth dependent on uptake of cyst(e)ine from their micro-environment. Accordingly, we previously suggested that the xc? plasma membrane cystine transporter provided a target for lymphoid cancer therapy. Its inhibition could lead to cyst(e)ine deficiency in lymphoma cells via reduction of both their cystine uptake and

  8. Activation of Transient Receptor Potential Vanilloid-3 Inhibits Human Hair Growth

    Microsoft Academic Search

    István Borbíró; Erika Lisztes; Balázs I Tóth; Gabriella Czifra; Attila Oláh; Attila G Szöll?si; Norbert Szentandrássy; Péter P Nánási; Zoltán Péter; Ralf Paus; László Kovács; Tamás Bíró

    2011-01-01

    In the current study, we aimed at identifying the functional role of transient receptor potential vanilloid-3 (TRPV3) ion channel in the regulation of human hair growth. Using human organ-cultured hair follicles (HFs) and cultures of human outer root sheath (ORS) keratinocytes, we provide the first evidence that activation of TRPV3 inhibits human hair growth. TRPV3 immunoreactivity was confined to epithelial

  9. Activin A Mediates Growth Inhibition and Cell Cycle Arrest through Smads in Human Breast Cancer Cells

    Microsoft Academic Search

    Joanna E. Burdette; Jacqueline S. Jeruss; Sarah J. Kurley; Eun Jig Lee; Teresa K. Woodruff

    The transforming growth factor-B (TGF-B) superfamily of growth factors is responsible for a variety of physiologic actions, including cell cycle regulation. Activin is a member of the TGF-B superfamily that inhibits the proliferation of breast cancer cells. Activin functions by interacting with its type I and type II receptors to induce phosphorylation of intra- cellular signaling molecules known as Smads.

  10. 6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice.

    PubMed

    Miao, Yong; Sun, Yabin; Wang, Wenjun; Du, Benjun; Xiao, Shun-e; Hu, Yijue; Hu, Zhiqi

    2013-01-01

    Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal. PMID:23437345

  11. Corrosion inhibition of mild steel in 1 M HCl solution by henna extract: A comparative study of the inhibition by henna and its constituents (Lawsone, Gallic acid, ?- d-Glucose and Tannic acid)

    Microsoft Academic Search

    A. Ostovari; S. M. Hoseinieh; M. Peikari; S. R. Shadizadeh; S. J. Hashemi

    2009-01-01

    The inhibitive action of henna extract (Lawsonia inermis) and its main constituents (lawsone, gallic acid, ?-d-Glucose and tannic acid) on corrosion of mild steel in 1M HCl solution was investigated through electrochemical techniques and surface analysis (SEM\\/EDS). Polarization measurements indicate that all the examined compounds act as a mixed inhibitor and inhibition efficiency increases with inhibitor concentration. Maximum inhibition efficiency

  12. Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

    SciTech Connect

    Wang, Wei, E-mail: weiwang2@illinois.edu; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbasava2@illinois.edu; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-01-15

    Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 31–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100 ?g/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1 mM). During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1 mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10 ?g/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5 mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. -- Highlights: ? DEHP inhibits growth and increases reactive oxygen species in ovarian antral follicles in vitro. ? NAC rescues the effects of DEHP on the growth and reactive oxygen species levels in follicles. ? DEHP decreases the expression and activity of Cu/Zn superoxide dismutase, which can be rescued by NAC, in antral follicles.

  13. Inhibition by boric acid of the oxidation of zirconium in high pressure steam

    Microsoft Academic Search

    C. F. Britton; J. N. Wanklyn

    1962-01-01

    A substantial reduction in the corrosion of iodide zirconium expused to ; high pressure steam has been obtained by adding boric acid to the steam. In ; steam only at 500 deg C and l000 psi (68 at.), iodide zirconium is almost ; completely oxidised in 24 hours, weight gains of about 5400 mg\\/dm² being ; obtained. Inhibition by boric

  14. Inhibition of lysosomal acid sphingomyelinase by agents which reverse multidrug resistance

    Microsoft Academic Search

    Jean-Pierre Jaffrézou; Gang Chen; George E. Durán; Catherine Muller; Christine Bordier; Guy Laurent; Branimir I. Sikic; Thierry Levade

    1995-01-01

    An increasing body of evidence appears to implicate the lipid bilayer of multidrug resistant (MDR) cells with P-glycoprotein activity. Several cationic amphiphilic drugs (CADs) have been extensively described as modulators of MDR. These same agents are also known to (1) inhibit lysosomal acid sphingomyelinase (ASmase), a phospholipid degrading enzyme, and\\/or (2) induce phospholipidosis in animal tissues or cultured cell lines.

  15. Zinc inhibition of -aminobutyric acid transporter 4 (GAT4) reveals a link between excitatory

    E-print Network

    Eskandari, Sepehr

    Zinc inhibition of -aminobutyric acid transporter 4 (GAT4) reveals a link between excitatory and extrasynaptic regions. In certain brain regions, vesic- ular zinc is colocalized and coreleased with glutamate of zinc on expressed GATs (GAT1, GAT2, GAT3, and GAT4) in Xenopus laevis oocytes by using tracer flux

  16. Inhibition of oxidation of omega-3 polyunsaturated fatty acids and fish oil by quercetin glycosides

    Microsoft Academic Search

    Gwendolyn M. Huber; H. P. Vasantha Rupasinghe; Fereidoon Shahidi

    2009-01-01

    The antioxidant properties of naturally occurring flavonols, quercetin glycosides, were examined and compared with common food antioxidants butylated hydroxytoluene (BHT) and ?-tocopherol. Antioxidants were incorporated into selected polyunsaturated fatty acids (PUFA) or fish oil in aqueous emulsions and bulk oil systems. The effectiveness of quercetin was similar to or greater than quercetin glycosides in inhibiting lipid oxidation in the oil-in-water

  17. RETINOIDAL BENZOIC ACIDS (AROTENOIDS) AND OTHER RETINOIDS INHIBIT IN VITRO TRANSFORMATION OF EPITHELIAL CELLS

    EPA Science Inventory

    Five retinoids were calcluated for their ability to inhibit N-methyl-N'nitro-N-nitrosoguanidine (MNNG)-induccd transformation of primary rat trachcal epithelial (RTE) cells in culture at concentrations that did not affect cell survival. wo retinoidal benzoic acids (arotcnoids), R...

  18. Inhibition of hypersensitivity of delayed and immediate types in guinea pigs by methylenediphosphonic acid

    Microsoft Academic Search

    S. V. Komissarenko; N. I. Zhuravskii; N. P. Karlova; M. F. Gulyi

    1977-01-01

    The effect of subcutaneous injection of the immunosuppressive agent methylene-diphosphonic acid (MDPA) on hypersensitivity of delayed and immediate types (HDT and HIT) was studied in guinea pigs. Administration of MDPA to the animals in a dose of 30 µg\\/g was found to inhibit HDT and HIT by 60–80% compared with the control.

  19. Polyunsaturated Fatty Acids Inhibit T Cell Signal Transduction by Modification of Detergent-insoluble Membrane Domains

    Microsoft Academic Search

    Thomas M. Stulnig; Markus Berger; Thomas Sigmund; Daniel Raederstorff; Hannes Stockinger; Werner Waldhäusl

    1998-01-01

    Polyunsaturated fatty acids (PUFAs) exert immunosuppressive effects, but the molecular alter- ations leading to T cell inhibition are not yet elucidated. Signal transduction seems to involve detergent-resis- tant membrane domains (DRMs) acting as functional rafts within the plasma membrane bilayer with Src fam- ily protein tyrosine kinases being attached to their cyto- plasmic leaflet. Since DRMs include predominantly sat- urated

  20. Synergistic inhibition of respiration in brain mitochondria by nitric oxide and dihydroxyphenylacetic acid (DOPAC)

    Microsoft Academic Search

    Carla Nunes; Leonor Almeida; João Laranjinha

    2005-01-01

    The inhibition of mitochondrial respiration by nitric oxide (NO) at cytochrome c oxidase level has been established as a physiological regulatory mechanism of mitochondrial function. Given, on the one hand, the potential involvement of NO and dopamine metabolism in mitochondrial dysfunction associated with neurodegeneration and, on the other hand, the reported interaction of NO with dihydroxyphenylacetic acid (DOPAC), a major

  1. Mycophenolic Acid Inhibits Dengue Virus Infection by Preventing Replication of Viral RNA

    Microsoft Academic Search

    Michael S. Diamond; Marcus Zachariah; Eva Harris

    2002-01-01

    Dengue fever is a mosquito-borne viral disease of global importance with no available antiviral therapy. We assessed the ability of mycophenolic acid (MPA), a drug currently used as an immunosuppressive agent, to inhibit dengue virus (DV) antigen expression, RNA replication, and virus production. Pharmacological concentrations of MPA effectively blocked DV infection, decreasing the percentage of infected cells by 99% and

  2. Asiatic Acid Inhibits Pro-Angiogenic Effects of VEGF and Human Gliomas in Endothelial Cell Culture Models

    PubMed Central

    Kavitha, Chandagirikoppal V.; Agarwal, Chapla; Agarwal, Rajesh; Deep, Gagan

    2011-01-01

    Malignant gliomas are one of the most devastating and incurable tumors. Sustained excessive angiogenesis by glioma cells is the major reason for their uncontrolled growth and resistance toward conventional therapies resulting in high mortality. Therefore, targeting angiogenesis should be a logical strategy to prevent or control glioma cell growth. Earlier studies have shown that Asiatic Acid (AsA), a pentacyclic triterpenoid, is effective against glioma and other cancer cells; however, its efficacy against angiogenesis remains unknown. In the present study, we examined the anti-angiogenic efficacy of AsA using human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC). Our results showed that AsA (5–20 µM) inhibits HUVEC growth and induces apoptotic cell death by activating caspases (3 and 9) and modulating the expression of apoptosis regulators Bad, survivin and pAkt-ser473. Further, AsA showed a dose-dependent inhibition of HUVEC migration, invasion and capillary tube formation, and disintegrated preformed capillary network. AsA also inhibited the VEGF-stimulated growth and capillary tube formation by HUVEC and HBMEC. Next, we analyzed the angiogenic potential of conditioned media collected from human glioma LN18 and U87-MG cells treated with either DMSO (control conditioned media, CCM) or AsA 20 µM (AsA20 conditioned media, AsA20CM). CCM from glioma cells significantly enhanced the capillary tube formation in both HUVEC and HBMEC, while capillary tube formation in both endothelial cell lines was greatly compromised in the presence of AsA20CM. Consistent with these results, VEGF expression was lesser in AsA20CM compared to CCM, and indeed AsA strongly inhibited VEGF level (both cellular and secreted) in glioma cells. AsA also showed dose-dependent anti-angiogenic efficacy in Matrigel plug assay, and inhibited the glioma cells potential to attract HUVEC/HBMEC. Overall, the present study clearly showed the strong anti-angiogenic potential of AsA and suggests its usefulness against malignant gliomas. PMID:21826202

  3. Comparison of toxicity to terrestrial plants with algal growth inhibition by herbicides

    SciTech Connect

    Garten, C.T. Jr.; Frank, M.L.

    1984-10-01

    The toxicities of 21 different herbicides to algae (Selenastrum capricornutum and Chlorella vulgaris) and to terrestrial plants (radishes, barley, and bush beans or soybeans) were compared to order to determine the feasibility of using a short-term (96-h) algal growth inhibition test for identifying chemicals having potential toxicity in a 4-week terrestrial plant bioassay. The toxicity of each test chemical, usually in combination with a commercial formulation, was evaluated at six nominal concentrations, between 0 and 100 mg/L growth medium in the algal bioassay or between 0 and 100 mg/kg substate in the terrestrial plant bioassay, in terms of both (1) the no-observed-effect concentration (NOEC), i.e., the highest concentration tested at which no significant (P < 0.05, one-sided test) reduction in algal growth rate or in terrestrial plant yield, relative to controls, was observed; and (2) the concentration at which algal growth rate or terrestrial plant yield was reduced by 50% or more relative to controls. There was generally poor agreement between results from the two types of bioassays; results from algal growth inhibition tests were not significantly correlated with results from the terrestrial plant bioassays. Overall, there was an approximately 50% chance of an algal bioassay, using Selenastrum capricornutum, successfully screening (detecting) herbicide levels that reduced terrestrial plant yield. The results indicated that algal growth inhibition tests cannot be used generically to predict phytotoxicity of herbicides to terrestrial plant species. 7 references, 14 tables.

  4. Regulation of legume nodulation by acidic growth conditions

    PubMed Central

    Ferguson, Brett J.; Lin, Meng-Han; Gresshoff, Peter M.

    2013-01-01

    Legumes represent some of the most important crop species worldwide. They are able to form novel root organs known as nodules, within which biological nitrogen fixation is facilitated through a symbiotic interaction with soil-dwelling bacteria called rhizobia. This provides legumes with a distinct advantage over other plant species, as nitrogen is a key factor for growth and development. Nodule formation is tightly regulated by the plant and can be inhibited by a number of external factors, such as soil pH. This is of significant agricultural and economic importance as much of global legume crops are grown on low pH soils. Despite this, the precise mechanism by which low pH conditions inhibits nodule development remains poorly characterized. PMID:23333963

  5. d-Amino Acids Do Not Inhibit Biofilm Formation in Staphylococcus aureus

    PubMed Central

    Sarkar, Sourav; Pires, Marcos M.

    2015-01-01

    Bacteria can either exist in the planktonic (free floating) state or in the biofilm (encased within an organic framework) state. Bacteria biofilms cause industrial concerns and medical complications and there has been a great deal of interest in the discovery of small molecule agents that can inhibit the formation of biofilms or disperse existing structures. Herein we show that, contrary to previously published reports, d-amino acids do not inhibit biofilm formation of Bacillus subtilis (B. subtilis), Staphylococcus aureus (S. aureus), and Staphylococcus epidermis (S. epidermis) at millimolar concentrations. We evaluated a diverse set of natural and unnatural d-amino acids and observed no activity from these compounds in inhibiting biofilm formation. PMID:25658642

  6. Fibroblast growth factor receptors as therapeutic targets in human melanoma: synergism with BRAF inhibition.

    PubMed

    Metzner, Thomas; Bedeir, Alexandra; Held, Gerlinde; Peter-Vörösmarty, Barbara; Ghassemi, Sara; Heinzle, Christine; Spiegl-Kreinecker, Sabine; Marian, Brigitte; Holzmann, Klaus; Grasl-Kraupp, Bettina; Pirker, Christine; Micksche, Michael; Berger, Walter; Heffeter, Petra; Grusch, Michael

    2011-10-01

    Cutaneous melanoma is a tumor with rising incidence and a very poor prognosis at the disseminated stage. Melanomas are characterized by frequent mutations in BRAF and also by overexpression of fibroblast growth factor 2 (FGF2), offering opportunities for therapeutic intervention. We investigated inhibition of FGF signaling and its combination with dacarbazine or BRAF inhibitors as an antitumor strategy in melanoma. The majority of melanoma cell lines displayed overexpression of FGF2 but also FGF5 and FGF18 together with different isoforms of FGF receptors (FGFRs) 1-4. Blockade of FGF signals with dominant-negative receptor constructs (dnFGFR1, 3, or 4) or small-molecule inhibitors (SU5402 and PD166866) reduced melanoma cell proliferation, colony formation, as well as anchorage-independent growth, and increased apoptosis. DnFGFR constructs also significantly inhibited tumor growth in vivo. Combination of FGF inhibitors with dacarbazine showed additive or antagonistic effects, whereas synergistic drug interaction was observed when combining FGFR inhibition with the multikinase/BRAF inhibitor sorafenib or the V600E mutant-specific BRAF inhibitor RG7204. In conclusion, FGFR inhibition has antitumor effects against melanoma cells in vitro and in vivo. Combination with BRAF inhibition offers a potential for synergistic antimelanoma effects and represents a promising therapeutic strategy against advanced melanoma. PMID:21753785

  7. Tie1 deletion inhibits tumor growth and improves angiopoietin antagonist therapy

    PubMed Central

    D’Amico, Gabriela; Korhonen, Emilia A.; Anisimov, Andrey; Zarkada, Georgia; Holopainen, Tanja; Hägerling, René; Kiefer, Friedemann; Eklund, Lauri; Sormunen, Raija; Elamaa, Harri; Brekken, Rolf A.; Adams, Ralf H.; Koh, Gou Young; Saharinen, Pipsa; Alitalo, Kari

    2014-01-01

    The endothelial Tie1 receptor is ligand-less, but interacts with the Tie2 receptor for angiopoietins (Angpt). Angpt2 is expressed in tumor blood vessels, and its blockade inhibits tumor angiogenesis. Here we found that Tie1 deletion from the endothelium of adult mice inhibits tumor angiogenesis and growth by decreasing endothelial cell survival in tumor vessels, without affecting normal vasculature. Treatment with VEGF or VEGFR-2 blocking antibodies similarly reduced tumor angiogenesis and growth; however, no additive inhibition was obtained by targeting both Tie1 and VEGF/VEGFR-2. In contrast, treatment of Tie1-deficient mice with a soluble form of the extracellular domain of Tie2, which blocks Angpt activity, resulted in additive inhibition of tumor growth. Notably, Tie1 deletion decreased sprouting angiogenesis and increased Notch pathway activity in the postnatal retinal vasculature, while pharmacological Notch suppression in the absence of Tie1 promoted retinal hypervasularization. Moreover, substantial additive inhibition of the retinal vascular front migration was observed when Angpt2 blocking antibodies were administered to Tie1-deficient pups. Thus, Tie1 regulates tumor angiogenesis, postnatal sprouting angiogenesis, and endothelial cell survival, which are controlled by VEGF, Angpt, and Notch signals. Our results suggest that targeting Tie1 in combination with Angpt/Tie2 has the potential to improve antiangiogenic therapy. PMID:24430181

  8. Optimization of peptides that target human thymidylate synthase to inhibit ovarian cancer cell growth.

    PubMed

    Pelà, Michela; Saxena, Puneet; Luciani, Rosaria; Santucci, Matteo; Ferrari, Stefania; Marverti, Gaetano; Marraccini, Chiara; Martello, Andrea; Pirondi, Silvia; Genovese, Filippo; Salvadori, Severo; D'Arca, Domenico; Ponterini, Glauco; Costi, Maria Paola; Guerrini, Remo

    2014-02-27

    Thymidylate synthase (TS) is a target for pemetrexed and the prodrug 5-fluorouracil (5-FU) that inhibit the protein by binding at its active site. Prolonged administration of these drugs causes TS overexpression, leading to drug resistance. The peptide lead, LR (LSCQLYQR), allosterically stabilizes the inactive form of the protein and inhibits ovarian cancer (OC) cell growth with stable TS and decreased dihydrofolate reductase (DHFR) expression. To improve TS inhibition and the anticancer effect, we have developed 35 peptides by modifying the lead. The d-glutamine-modified peptide displayed the best inhibition of cisplatin-sensitive and -resistant OC cell growth, was more active than LR and 5-FU, and showed a TS/DHFR expression pattern similar to LR. Circular dichroism spectroscopy and molecular dynamics studies provided a molecular-level rationale for the differences in structural preferences and the enzyme inhibitory activities. By combining target inhibition studies and the modulation pattern of associated proteins, this work avenues a concept to develop more specific inhibitors of OC cell growth and drug leads. PMID:24450514

  9. MPP+ induced SH-SY5Y apoptosis is potentiated by cyclosporin A and inhibited by aristolochic acid

    Microsoft Academic Search

    Christopher P Fall; James P Bennett

    1998-01-01

    In experiments investigating the role of the mitochondrial transition pore (MTP) in apoptosis induced by the Parkinsonism producing toxin N-methyl pyridinium ion (MPP+), we attempted to block possible MTP opening with cyclosporin A (CSA) alone or in combination with the phospholipase A2 (PLA2) inhibitor aristolochic acid (ARA). Paradoxically, CSA potentiated rather than inhibited MPP+ induced apoptosis. Aristolochic acid alone inhibited

  10. Polyphenols from green tea inhibit the growth of melanoma cells through inhibition of class I histone deacetylases and induction of DNA damage

    PubMed Central

    Prasad, Ram; Katiyar, Santosh K.

    2015-01-01

    Melanoma is the leading cause of skin cancer-related deaths. We have examined the effect of green tea polyphenols (GTPs), a natural mixture of epicatechin monomers, on melanoma cancer cell growth and the molecular mechanism underlying these effects using different human melanoma cell lines as an in vitro model. Treatment of melanoma cell lines (A375, Hs294t, SK-Mel28 and SK-Mel119) with GTPs significantly inhibited the cell viability as well as colony formation ability of melanoma cells in a dose-dependent manner. These effects of GTPs were associated with a significant inhibition of histone deacetylase (HDAC) activity, reduction in the levels of class I HDAC proteins, enhancement of histone acetyltransferase (HAT) activity and induction of DNA damage, as detected by Comet assay, in melanoma cells. GTPs-induced decrease in the levels of class I HDAC proteins is mediated through proteasomal degradation. Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of melanoma cells. Treatment of A375 and Hs294t cells with GTPs resulted in a decrease in the levels of cyclins and cyclin dependent kinases of G1 phase of cell cycle whereas upregulated the levels of tumor suppressor proteins (Cip1/WAF1/p21, p16 and p53). PMID:25821561

  11. Elevated major ion concentrations inhibit larval mayfly growth and development.

    PubMed

    Johnson, Brent R; Weaver, Paul C; Nietch, Christopher T; Lazorchak, James M; Struewing, Katherine A; Funk, David H

    2015-01-01

    Anthropogenic disturbances, including those from developing energy resources, can alter stream chemistry significantly by elevating total dissolved solids. Field studies have indicated that mayflies (Order Ephemeroptera) are particularly sensitive to high total dissolved solids. In the present study, the authors measured 20-d growth and survivorship of larval Neocloeon triangulifer exposed to a gradient of brine salt (mixed NaCl and CaCl2 ) concentrations. Daily growth rates were reduced significantly in all salt concentrations above the control (363?µS?cm(-1) ) and larvae in treatments with specific conductance >812?µS?cm(-1) were in comparatively earlier developmental stages (instars) at the end of the experiment. Survivorship declined significantly when specific conductance was >1513?µS?cm(-1) and the calculated 20-d 50% lethal concentration was 2866?µS?cm(-1) . The present study's results provide strong experimental evidence that elevated ion concentrations similar to those observed in developing energy resources, such as oil and gas drilling or coal mining, can adversely affect sensitive aquatic insect species. PMID:25307284

  12. Pharmacologic inhibition of MEK signaling prevents growth of canine hemangiosarcoma

    PubMed Central

    Andersen, Nicholas J.; Nickoloff, Brian J.; Dykema, Karl J.; Boguslawski, Elissa A.; Krivochenitser, Roman I.; Froman, Roe E.; Dawes, Michelle J.; Baker, Laurence H.; Thomas, Dafydd G.; Kamstock, Debra A.; Kitchell, Barbara E.; Furge, Kyle A.; Duesbery, Nicholas S.

    2013-01-01

    Angiosarcoma (AS) is a rare neoplasm of endothelial origin that has limited treatment options and poor five-year survival. As a model for human AS, we studied primary cells and tumorgrafts derived from canine hemangiosarcoma (HSA), which is also an endothelial malignancy with similar presentation and histology. Primary cells isolated from HSA showed constitutive ERK activation. The MEK inhibitor CI-1040 reduced ERK activation and the viability of primary cells derived from visceral, cutaneous, and cardiac HSA in vitro. HSA-derived primary cells were also sensitive to sorafenib, an inhibitor of B-Raf and multi-receptor tyrosine kinases. In vivo, CI-1040 or PD0325901 decreased the growth of cutaneous cell-derived xenografts and cardiac-derived tumorgrafts. Sorafenib decreased tumor size in both in vivo models, although cardiac tumorgrafts were more sensitive. In human AS, we noted that 50% of tumors stained positively for phosphorylated ERK1/2 and that the expression of several MEK-responsive transcription factors was up-regulated. Our data showed that MEK signaling is essential for the growth of HSA in vitro and in vivo and provided evidence that the same pathways are activated in human AS. This indicates that MEK inhibitors may form part of an effective therapeutic strategy for the treatment of canine HSA or human AS, and it highlights the utility of spontaneous canine cancers as a model of human disease. PMID:23804705

  13. Influence of amino acids on nitrogen fixation ability and growth of Azospirillum spp.

    PubMed Central

    Hartmann, A; Fu, H A; Burris, R H

    1988-01-01

    The utilization of amino acids for growth and their effects on nitrogen fixation differ greatly among the several strains of each species of Azospirillum spp. that were examined. A. brasiliense grew poorly or not at all on glutamate, aspartate, serine, or histidine as the sole nitrogen and carbon sources. Nitrogen fixation by most A. brasiliense strains was inhibited only slightly even by 10 mM concentrations of these amino acids. In contrast, A. lipoferum and A. amazonense grew very well on glutamate, aspartate, serine, or histidine as the sole nitrogen and carbon sources; nitrogen fixation, which was measured in the presence of malate or sucrose, was severely