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1

Glycyrrhizic acid inhibits virus growth and inactivates virus particles  

Microsoft Academic Search

Screening investigations in antiviral action of plant extracts have revealed that a component of Glycyrrhiza glabra roots, found to be glycyrrhizic 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

Raffaello Pompei; Ornella Flore; Maria Antonietta Marccialis; Alessandra Pani; Bernardo Loddo

1979-01-01

2

Cinnamic Acid Increases Lignin Production and Inhibits Soybean Root Growth  

PubMed Central

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

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

3

Gymnemic acids inhibit hyphal growth and virulence in Candida albicans.  

PubMed

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

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

2013-01-01

4

Gymnemic Acids Inhibit Hyphal Growth and Virulence in Candida albicans  

PubMed Central

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

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

2013-01-01

5

Salicylic acid antagonizes abscisic acid inhibition of shoot growth and cell cycle progression in rice  

NASA Astrophysics Data System (ADS)

We analysed effects of abscisic acid (ABA, a negative regulatory hormone), alone and in combination with positive or neutral hormones, including salicylic acid (SA), on rice growth and expression of cell cycle-related genes. ABA significantly inhibited shoot growth and induced expression of OsKRP4, OsKRP5, and OsKRP6. A yeast two-hybrid assay showed that OsKRP4, OsKRP5, and OsKRP6 interacted with OsCDKA;1 and/or OsCDKA;2. When SA was simultaneously supplied with ABA, the antagonistic effect of SA completely blocked ABA inhibition. SA also blocked ABA inhibition of DNA replication and thymidine incorporation in the shoot apical meristem. These results suggest that ABA arrests cell cycle progression by inducing expression of OsKRP4, OsKRP5, and OsKRP6, which inhibit the G1/S transition, and that SA antagonizes ABA by blocking expression of OsKRP genes.

Meguro, Ayano; Sato, Yutaka

2014-04-01

6

Inhibition of enterobacteria and Listeria growth by lactic, acetic and formic acids.  

PubMed

Minimum inhibitory concentrations (MIC) of undissociated lactic, acetic and formic acids were evaluated for 23 strains of enterobacteria and two of Listeria monocytogenes. The evaluation was performed aerobically and anaerobically in a liquid test system at pH intervals of between 4.2 and 5.4. Growth of the enterobacteria was inhibited at 2-11 mmol l-1, 0.5-14 mmol l-1 and 0.1-1.5 mmol l-1 of undissociated lactic, acetic and formic acids, respectively. The MIC value was slightly lower with anaerobic conditions compared with aerobic conditions. The influence of protons on the inhibition was observed for acetic acid at the low pH values. Undissociated lactic acid was 2 to 5 times more efficient in inhibiting L. monocytogenes than enterobacteria. Acetic acid had a similar inhibitory action on L. monocytogenes compared with enterobacteria. Inorganic acid (HCl) inhibited most enterobacteria at pH 4.0; some strains, however, were able to initiate growth to pH 3.8. The results indicate that the values of undissociated acid which occur in a silage of pH 4.1-4.5 are about 10-100 times higher than required in order to protect the forage from the growth of enterobacteria and L. monocytogenes. PMID:8365950

Ostling, C E; Lindgren, S E

1993-07-01

7

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

PubMed

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

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

2012-08-01

8

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

PubMed Central

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

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

2012-01-01

9

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

PubMed Central

Epidemiological and preclinical evidence supports that omega-3 dietary fatty acids (fish oil) reduce the risks of macular degeneration and cancers, but the mechanisms by which these omega-3 lipids inhibit angiogenesis and tumorigenesis are poorly understood. Here we show that epoxydocosapentaenoic acids (EDPs), which are lipid mediators produced by cytochrome P450 epoxygenases from omega-3 fatty acid docosahexaenoic acid, inhibit VEGF- and fibroblast growth factor 2-induced angiogenesis in vivo, and suppress endothelial cell migration and protease production in vitro via a VEGF receptor 2-dependent mechanism. When EDPs (0.05 mg?kg?1?d?1) are coadministered with a low-dose soluble epoxide hydrolase inhibitor, EDPs are stabilized in circulation, causing ?70% inhibition of primary tumor growth and metastasis. Contrary to the effects of EDPs, the corresponding metabolites derived from omega-6 arachidonic acid, epoxyeicosatrienoic acids, increase angiogenesis and tumor progression. These results designate epoxyeicosatrienoic acids and EDPs as unique endogenous mediators of an angiogenic switch to regulate tumorigenesis and implicate a unique mechanistic linkage between omega-3 and omega-6 fatty acids and cancers. PMID:23553837

Zhang, Guodong; Panigrahy, Dipak; Mahakian, Lisa M.; Yang, Jun; Liu, Jun-Yan; Stephen Lee, Kin Sing; Wettersten, Hiromi I.; Ulu, Arzu; Hu, Xiaowen; Tam, Sarah; Hwang, Sung Hee; Ingham, Elizabeth S.; Kieran, Mark W.; Weiss, Robert H.; Ferrara, Katherine W.; Hammock, Bruce D.

2013-01-01

10

Inhibition of poxvirus growth by Terameprocol, a methylated derivative of nordihydroguaiaretic acid.  

PubMed

Terameprocol (TMP) is a methylated derivative of nordihydroguaiaretic acid, a phenolic antioxidant originally derived from creosote bush extracts. TMP has previously been shown to have antiviral and anti-inflammatory activities, and has been proven safe in phase I clinical trials conducted to evaluate TMP as both a topical and parenteral therapeutic. In the current study, we examined the ability of TMP to inhibit poxvirus growth in vitro, and found that TMP potently inhibited the growth of both cowpox virus and vaccinia virus in a variety of cell lines. TMP treatment was highly effective at reducing infectious virus yield in multi-step virus growth assays, but it did not substantially inhibit the synthesis of infectious progeny viruses in individual infected cells. These contrasting results showed that TMP inhibits poxvirus growth in vitro by preventing the efficient spread of virus particles from cell to cell. The canonical mechanism of poxvirus cell-to-cell spread requires morphogenesis of cell-associated, enveloped virions. The virions then trigger the formation of actin tails to project them from the cell surface. The number of actin tails present at the surface of poxvirus-infected cells was reduced dramatically by treatment with TMP. Whether TMP inhibits poxvirus morphogenesis, or subsequent events required for actin tail formation, remains to be determined. The results of this study, together with the clinical safety record of TMP, support further evaluation of TMP as a poxvirus therapeutic. PMID:20888364

Pollara, Justin J; Laster, Scott M; Petty, Ian T D

2010-12-01

11

Plant growth inhibition by cis-cinnamoyl glucosides and cis-cinnamic acid.  

PubMed

Spiraea thunbergii Sieb. contains 1-O-cis-cinnamoyl-beta-D-glucopyranose (CG) and 6-O-(4'-hydroxy-2'-methylene-butyroyl)-1-O-cis-cinnamoyl-beta-D-glucopyranose (BCG) as major plant growth inhibiting constituents. In the present study, we determined the inhibitory activity of CG and BCG on root elongation of germinated seedlings of lettuce (Lactuca sativa), pigweed (Amaranthus retroflexus), red clover (Trifolium pratense), timothy (Phleum pratense), and bok choy (Brassica rapa var chinensis) in comparison with that of two well-known growth inhibitors, 2,4-dichlorophenoxyacetic acid (2,4-D) and (+)-2-cis-4-trans-abscisic acid (cis-ABA), as well as two related chemicals of CG and BCG, cis-cinnamic acid (cis-CA) and trans-cinnamic acid (trans-CA). The EC50 values for CG and BCG on lettuce were roughly one-half to one-quarter of the value for cis-ABA. cis-Cinnamic acid, which is a component of CG and BCG, possessed almost the same inhibitory activity of CG and BCG, suggesting that the essential chemical structure responsible for the inhibitory activity of CG and BCG is cis-CA. The cis-stereochemistry of the methylene moiety is apparently needed for high inhibitory activity, as trans-CA had an EC50 value roughly 100 times that of CG, BCG, and cis-CA. Growth inhibition by CG, BCG, and cis-CA was influenced by the nature of the soil in the growing medium: alluvial soil preserved the bioactivity, whereas volcanic ash and calcareous soils inhibited bioactivity. These findings indicate a potential role of cis-CA and its glucosides as allelochemicals for use as plant growth regulators in agricultural fields. PMID:15898503

Hiradate, Syuntaro; Morita, Sayaka; Furubayashi, Akihiro; Fujii, Yoshiharu; Harada, Jiro

2005-03-01

12

Acetyl11Keto -Boswellic Acid Inhibits Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis  

Microsoft Academic Search

The role of angiogenesis in tumor growth and metastasis is well established. Identification of a small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we showed that acetyl-11-keto-B-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor

Xiufeng Pang; Zhengfang Yi; Xiaoli Zhang; Bokyung Sung; Weijing Qu; Xiaoyuan Lian; Bharat B. Aggarwal; M. Liu

2009-01-01

13

Endophytic bacteria improve seedling growth of sunflower under water stress, produce salicylic acid, and inhibit growth of pathogenic fungi.  

PubMed

Endophytic bacterial strains SF2 (99.9% homology with Achromobacter xylosoxidans), and SF3 and SF4 (99.9% homology with Bacillus pumilus) isolated from sunflower grown under irrigation or drought were selected on the basis of plant growth-promoting bacteria (PGPB) characteristics. Aims of the study were to examine effects of inoculation with SF2, SF3, and SF4 on sunflower cultivated under water stress, to evaluate salicylic acid (SA) production by these strains in control medium or at ?a = -2.03 MPa, and to analyze effects of exogenously applied SA, jasmonic acid (JA), bacterial pellets, and bacterial supernatants on growth of pathogenic fungi Alternaria sp., Sclerotinia sp., and Verticillum sp. Growth response to bacterial inoculation was studied in two inbred lines (water stress-sensitive B59 and water stress-tolerant B71) and commercial hybrid Paraiso 24. Under both water stress and normal conditions, plant growth following inoculation was more strongly enhanced for Paraiso 24 and B71 than for B59. All three strains produced SA in control medium; levels for SF3 and SF4 were higher than for SF2. SA production was dramatically higher at ?a = -2.03 MPa. Exogenously applied SA or JA caused a significant reduction of growth for Sclerotinia and a lesser reduction for Alternaria and Verticillum. Fungal growth was more strongly inhibited by bacterial pellets than by bacterial supernatants. Our findings indicate that these endophytic bacteria enhance growth of sunflower seedlings under water stress, produce SA, and inhibit growth of pathogenic fungi. These characteristics are useful for formulation of inoculants to improve growth and yield of sunflower crops. PMID:20383767

Forchetti, Gabriela; Masciarelli, Oscar; Izaguirre, María J; Alemano, Sergio; Alvarez, Daniel; Abdala, Guillermina

2010-12-01

14

Acetyl-11-Keto-?-Boswellic Acid Inhibits Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis  

PubMed Central

The role of angiogenesis in tumor growth and metastasis is well established. Identification of small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we demonstrated that acetyl-11-keto-?-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg of AKBA) after solid tumors reached about 100 mm3 (n=5). The inhibitory effect of AKBA on tumor growth was well correlated with suppression of angiogenesis. When examined for the molecular mechanism, we found that AKBA significantly inhibited blood vessel formation in the Matrigel plug assay in mice and effectively and suppressed vascular endothelial growth factor (VEGF)-induced microvessel sprouting in rat aortic ring assay ex vivo. Furthermore, AKBA inhibited VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures from primary cultured human umbilical vascular endothelial cells (HUVECs) in a dose-dependent manner. Western blot analysis and in vitro kinase assay revealed that AKBA suppressed VEGF-induced phosphorylation of VEGF receptor 2 kinase (KDR/Flk-1) with IC50 of 1.68 ?mol/L. Specifically, AKBA suppressed the downstream protein kinases of VEGFR2, including Src family kinase, focal adhesion kinase, extracellular signal-related kinase, AKT, mTOR, and ribosomal protein S6 kinase. Our findings suggest that AKBA potently inhibits human prostate tumor growth through inhibition of angiogenesis induced by VEGFR2 signaling pathways. PMID:19567671

Pang, Xiufeng; Yi, Zhengfang; Zhang, Xiaoli; Sung, Bokyung; Qu, Weijing; Lian, Xiaoyuan; Aggarwal, Bharat B.; Liu, Mingyao

2009-01-01

15

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

E-print Network

and preclinical evidence supports that omega-3 dietary fatty acids (fish oil) reduce the risks of macular degenera- tion and cancers, but the mechanisms by which these omega-3 lipids inhibit angiogenesis mediators produced by cytochrome P450 epoxyge- nases from omega-3 fatty acid docosahexaenoic acid, inhibit

Hammock, Bruce D.

16

Capric acid secreted by S. boulardii inhibits C. albicans filamentous growth, adhesion and biofilm formation.  

PubMed

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

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

2010-01-01

17

The Weak Acid Preservative Sorbic Acid Inhibits Conidial Germination and Mycelial Growth of Aspergillus niger through Intracellular Acidification  

PubMed Central

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 lower. The MIC for conidia and, to a lesser extent, mycelia was shown to be dependent on the inoculum size. A. niger is capable of degrading sorbic acid, and this ability has consequences for food preservation strategies. The mechanism of action of sorbic acid was investigated using 31P nuclear magnetic resonance (NMR) spectroscopy. We show that a rapid decline in cytosolic pH (pHcyt) by more than 1 pH unit and a depression of vacuolar pH (pHvac) in A. niger occurs in the presence of sorbic acid. The pH gradient over the vacuole completely collapsed as a result of the decline in pHcyt. NMR spectra also revealed that sorbic acid (3.0 mM at pH 4.0) caused intracellular ATP pools and levels of sugar-phosphomonoesters and -phosphodiesters of A. niger mycelia to decrease dramatically, and they did not recover. The disruption of pH homeostasis by sorbic acid at concentrations below the MIC could account for the delay in spore germination and retardation of the onset of subsequent mycelial growth. PMID:15184150

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

2004-01-01

18

Growth Inhibition of Murine Melanoma Cells by Antibodies to a Cell Surface Glycoprotein Implicated in Retinoic Acid Action1  

Microsoft Academic Search

Previous studies have shown that treatment of S91-C2 murine mela noma cells with 0-a\\\\\\\\-trans-retinoic acid (RA) results in growth inhibition, enhanced activity of siaiyltransferase, and increased glycosylation of a M, 160,000cell surface sialoglycoprotein(gpl60). None of these effects could be detected in mutant clones (e.g., S91-C154) selected from the S91-C2 cells for resistance to RA-induced growth inhibition. These findings suggest that

Reuben Lotan; Yarda Deutsch; Israel Â

19

Calcite growth-rate inhibition by fulvic acid and magnesium ion—Possible influence on biogenic calcite formation  

NASA Astrophysics Data System (ADS)

Increases in ocean surface water dissolved carbon dioxide (CO2) concentrations retard biocalcification by reducing calcite supersaturation (?c). Reduced calcification rates may influence growth-rate dependent magnesium ion (Mg) incorporation into biogenic calcite modifying the use of calcifying organisms as paleoclimate proxies. Fulvic acid (FA) at biocalcification sites may further reduce calcification rates. Calcite growth-rate inhibition by FA and Mg, two common constituents of seawater and soil water involved in the formation of biogenic calcite, was measured separately and in combination under identical, highly reproducible experimental conditions. Calcite growth rates (pH=8.5 and ?c=4.5) are reduced by FA (0.5 mg/L) to 47% and by Mg (10-4 M) to 38%, compared to control experiments containing no added growth-rate inhibitor. Humic acid (HA) is twice as effective a calcite growth-rate inhibitor as FA. Calcite growth rate in the presence of both FA (0.5 mg/L) and Mg (10-4 M) is reduced to 5% of the control rate. Mg inhibits calcite growth rates by substitution for calcium ion at the growth site. In contrast, FA inhibits calcite growth rates by binding multiple carboxylate groups on the calcite surface. FA and Mg together have an increased affinity for the calcite growth sites reducing calcite growth rates.

Reddy, Michael M.

2012-08-01

20

Calcite growth-rate inhibition by fulvic acid and magnesium ion—Possible influence on biogenic calcite formation  

USGS Publications Warehouse

Increases in ocean surface water dissolved carbon dioxide (CO2) concentrations retard biocalcification by reducing calcite supersaturation (?c). Reduced calcification rates may influence growth-rate dependent magnesium ion (Mg) incorporation into biogenic calcite modifying the use of calcifying organisms as paleoclimate proxies. Fulvic acid (FA) at biocalcification sites may further reduce calcification rates. Calcite growth-rate inhibition by FA and Mg, two common constituents of seawater and soil water involved in the formation of biogenic calcite, was measured separately and in combination under identical, highly reproducible experimental conditions. Calcite growth rates (pH=8.5 and ?c=4.5) are reduced by FA (0.5 mg/L) to 47% and by Mg (10?4 M) to 38%, compared to control experiments containing no added growth-rate inhibitor. Humic acid (HA) is twice as effective a calcite growth-rate inhibitor as FA. Calcite growth rate in the presence of both FA (0.5 mg/L) and Mg (10?4 M) is reduced to 5% of the control rate. Mg inhibits calcite growth rates by substitution for calcium ion at the growth site. In contrast, FA inhibits calcite growth rates by binding multiple carboxylate groups on the calcite surface. FA and Mg together have an increased affinity for the calcite growth sites reducing calcite growth rates.

Reddy, Michael M.

2012-01-01

21

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

PubMed Central

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

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

2001-01-01

22

Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2  

PubMed Central

The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)—eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)—inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo. PMID:23892603

Parkinson, Eric Kenneth

2013-01-01

23

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...

24

Reversal of Glyphosate Inhibition of Carrot Cell Culture Growth by Glycolytic Intermediates and Organic and Amino Acids 1  

PubMed Central

Various cytokinins and purines were ineffective in reversing glyphosate (0.25 millimolar)-induced growth inhibition of carrot (Daucus carota L.) cell suspension cultures. Aspartate was particularly effective in reversing glyphosate inhibition, but asparagine and various combinations of lysine, methionine, threonine, and homoserine (eventual products of aspartate metabolism) were not effective. When organic acids of the tricarboxylic acid cycle were added to the medium, particularly good reversal of inhibition could be obtained with ?-ketoglutarate, succinate, and malate. Citrate provided only moderate reversal but the reversal given by glutamate was comparable to that of aspartate and the more effective tricarboxylic acid cycle intermediates. Pyruvate was somewhat toxic to cells when added early in the cell cycle but was most effective at reversing glyphosate inhibition when added at this time. If pyruvate addition was delayed, it was less toxic but was also a less effective reversing agent for glyphosate inhibition. All of the effective reversing agents for glyphosate inhibition found in this study can serve either directly or indirectly as carbon skeletons for respiration and ammonia assimilation and have previously been shown to be effective detoxifying agents for ammonia in cell culture systems. The results of this study suggest that glyphosate inhibition of growth in this system may be due to depletion of respiratory substrate which may eventually result in ammonia accumulation. PMID:16662096

Killmer, John; Widholm, Jack; Slife, Fred

1981-01-01

25

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

PubMed Central

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

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

26

Omega-3 Fatty Acids and Other FFA4 Agonists Inhibit Growth Factor Signaling in Human Prostate Cancer Cells.  

PubMed

Omega-3 fatty acids (n-3 FAs) are proposed to have many beneficial effects on human health. However, the mechanisms underlying their potential cancer preventative effects are unclear. G protein-coupled receptors (GPCRs) of the free fatty acid receptor (FFAR) family, FFA1/GPR40 and FFA4/GPR120, specifically bind n-3 FAs as agonist ligands. In this study, we examined the effects of n-3 FAs in human prostate cancer cell lines. Initial studies established that the long-chain n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid, inhibit proliferation of DU145 cells in response to lysophosphatidic acid (LPA), a mitogenic lipid mediator. When added alone to serum-starved DU145 cells, EPA transiently activates signaling events, including p70S6K phosphorylation. However, when added 15 minutes prior to LPA, EPA suppresses LPA-induced activating phosphorylations of ERK, FAK, and p70S6K, and expression of the matricellular protein CCN1. The rapid onset of the inhibitory action of EPA suggested involvement of a GPCR. Further studies showed that DU145 and PC-3 cells express mRNA and protein for both FFA4 and FFA1. TUG-891 (4-[(4-fluoro-4'-methyl[1,1'-biphenyl]-2-yl)methoxy]-benzenepropanoic acid), a selective agonist for FFA4, exerts inhibitory effects on LPA- and epidermal growth factor-induced proliferation and migration, similar to EPA, in DU145 and PC-3 cells. The effects of TUG-891 and EPA are readily reversible. The FFA1/FFA4 agonist GW9508 (4-[[(3-phenoxyphenyl)methyl]amino]-benzenepropranoic acid) likewise inhibits proliferation at doses that block FFA4. Knockdown of FFA4 expression prevents EPA- and TUG-891-induced inhibition of growth and migration. Together, these results indicate that activation of FFA4 initiates signaling events that can inhibit growth factor-induced signaling, providing a novel mechanism for suppression of cancer cell proliferation. PMID:25491146

Liu, Ze; Hopkins, Mandi M; Zhang, Zhihong; Quisenberry, Chrystal B; Fix, Louise C; Galvan, Brianna M; Meier, Kathryn E

2015-02-01

27

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

Microsoft Academic Search

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

Liam Good; Peter E. Nielsen

1998-01-01

28

Retinoic acid decreases ATF-2 phosphorylation and sensitizes melanoma cells to taxol-mediated growth inhibition  

PubMed Central

Cutaneous melanoma is often resistant to chemo- and radiotherapy. This resistance has recently been demonstrated to be due, at least in part, to high activating transcription factor 2 (ATF-2) activity in these tumors. In concordance with these reports, we found that B16 mouse melanoma cells had higher levels of ATF-2 than immortalized, but non-malignant mouse melanocytes. In addition, the melanoma cells had a much higher amount of phosphorylated (active) ATF-2 than the immortalized melanocytes. In the course of determining how retinoic acid (RA) stimulates activating protein-1 (AP-1) activity in B16 melanoma, we discovered that this retinoid decreased the phosphorylation of ATF-2. It appears that this effect is mediated through p38 MAPK, because RA decreased p38 phosphorylation, and a selective inhibitor of p38 MAPK (SB203580) also inhibited the phosphorylation of ATF-2. Since ATF-2 activity appears to be involved in resistance of melanoma to chemotherapy, we tested the hypothesis that treatment of the melanoma cells with RA would sensitize them to the growth-inhibitory effect of taxol. We found that pretreatment of B16 cells with RA decreased the IC50 from 50 nM to 1 nM taxol. On the basis of these findings and our previous work on AP-1, we propose a model in which treatment of B16 cells with RA decreases the phosphorylation of ATF-2, which results in less dimer formation with Jun. The "freed-up" Jun can then form a heterodimer with Fos, resulting in the increased AP-1 activity observed in RA-treated B16 cells. Shifting the balance from predominantly ATF-2:Jun dimers to a higher amount of Jun:Fos dimers could lead a change in target gene expression that reduces resistance to chemotherapeutic drugs and contributes to the pathway by which RA arrests proliferation and induces differentiation. PMID:18269766

Huang, Ying; Minigh, Jennifer; Miles, Sarah; Niles, Richard M

2008-01-01

29

Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth  

Microsoft Academic Search

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with

Paola Costelli; Marta Llovera; Joaquín López-Soriano; Neus Carbó; Luciana Tessitore; Francisco J. López-Soriano; Francesco M. Baccino; Josep M. Argilés

1995-01-01

30

Solubility, inhibited growth and dissolution kinetics of calcium oxalate crystals in solutions, containing hippuric acid  

Microsoft Academic Search

An analysis of crystal growth and dissolution of slightly soluble salts in physiological solutions in the presence of complexing ions was carried out, simulating conditions typical in human urine. It was found that hippuric acid, a normal physiological constituent of urine, acts at increased concentrations as a dissolving agent with respect to calcium oxalate (CaOx) and CaOx calculi. The kinetics

I. Gutzow; S. Atanassova; G. Budevsky; K. Neykov

1993-01-01

31

Lactic acid inhibition of the growth of spoilage bacteria and cold tolerant pathogens on pork.  

PubMed

The antibacterial effects of a 3% solution of lactic acid at 55 degrees C were assessed, by examining aerobic bacterial growth on artificially-inoculated pork fat and lean tissue. Discs of fat or lean tissues, each of 10 cm2 surface area, were aseptically excised from pork Longissimus dorsi muscle and inoculated with the cold tolerant pathogens Listeria monocytogenes 4b Scott A no. 3, Yersinia enterocolitica 0:4,32 or Aeromonas hydrophila ATCC 7966, or with the wild type spoilage bacteria Pseudomonas fragi or Brochothrix thermosphacta. After inoculation, each meat disc was immersed in water or lactic acid for 15 s and aerobic bacterial growth followed during 15 days of storage at 4 degrees C. P. fragi and B. thermosphacta grew on both fat and lean, but the pathogens grew on fat tissue only and A. hydrophila did not survive on lean. Lactic acid reduced all test bacteria on fat to below detectable levels within 4 days of treatment and no bacteria could be recovered from acid-treated fat surfaces for the remainder of the 15-day storage interval. Bacteria attached to lean were generally more resistant to lactic acid. In some instances the acid was bacteriostatic (P. fragi, L. monocytogenes) while in others the population declined at a greatly reduced rate as compared with a similar population on fat (B. thermosphacta, Y. enterocolitica). A. hydrophila was equally sensitive to lactic acid on lean and fat. Depending upon the tested strain, tissue type and storage time, maximum reductions in the number of bacteria recovered from acid treated pork ranged from 1 to 8 log cycles. The high bactericidal efficacy of lactic acid applied to pork fat was attributable to a low tissue pH, which varied from 3.49 to 4.41 during the 15 days of aerobic storage. PMID:7547145

Greer, G G; Dilts, B D

1995-04-01

32

Combined effects of carbonation with heating and fatty acid esters on inactivation and growth inhibition of various bacillus spores.  

PubMed

The effects of carbonation treatment (1 to 5 MPa, 30 min) plus heat treatment (30 to 80°C, 30 min) in the presence of various fatty acid esters (FAEs; 0.05 and 0.1%, wt/vol) on counts of viable Bacillus subtilis spores were investigated. FAEs or carbonation alone had no inactivation or growth inhibition effects on B. subtilis spores. However, carbonation plus heat (CH; 80°C, 5 MPa, 30 min) in the presence of mono- and diglycerol fatty acid esters markedly decreased counts of viable spores, and the spore counts did not change during storage for 30 days. The greatest decrease in viable spore counts occurred in the presence of monoglycerol fatty acid esters. Under CH conditions, inactivation and/or growth inhibition occurred at only 80°C and increased with increasing pressure. The greatest decrease in spore counts (more than 4 log units) occurred with CH (80°C, 5 MPa, 30 min) in the presence of monoglycerol fatty acid esters. However, this treatment was less effective against Bacillus coagulans and Geobacillus stearothermophilus spores. PMID:23992501

Klangpetch, Wannaporn; Nakai, Tomoe; Noma, Seiji; Igura, Noriyuki; Shimoda, Mitsuya

2013-09-01

33

Caffeic acid phenethyl ester decreases cholangiocarcinoma growth by inhibition of NF-?B and induction of apoptosis  

PubMed Central

Caffeic acid phenethyl ester (CAPE) inhibits the growth of tumor cells and is a known inhibitor of NF-?B that is constitutively active in cholangiocarcinoma (CCH) cells. We evaluated the effects of CAPE on CCH growth both in vitro and in vivo. Inhibition of NF-?B DNA-binding activity was confirmed in nuclear extracts treated with CAPE at 50, 40 and 20 ?M. CAPE decreases the expression of NF-?B1 (p50) and RelA (p65). CAPE decreased the growth of a number of CCH cells but not normal cholangiocytes. Cell cycle decrease was seen by a decrease in PCNA protein expression and the number of BrdU-positive cells treated with CAPE at 20 ?M compared to vehicle. Inhibition of growth and increased cell cycle arrest of Mz-ChA-1 cells by CAPE were coupled with increased apoptosis. Bax expression was increased, whereas Bcl-2 was decreased in cells treated with CAPE compared to vehicle. In vivo studies were performed in BALB/c nude (nu/nu) mice implanted subcutaneously with Mz-ChA-1 cells and treated with daily IP injections of DMSO or CAPE (10 mg/kg body weight in DMSO) for 77 days. Tumor growth was decreased and tumor latency was increased 2-fold in CAPE compared to vehicle-treated nude mice. In tumor samples, decreased CCH growth by CAPE was coupled with increased apoptosis. CAPE both in vivo and in vitro decreases the growth of cholangiocarcinoma cells by increasing apoptosis. These results demonstrate that CAPE might be an important therapeutic tool in the treatment of CCH. PMID:19358267

Onori, Paolo; DeMorrow, Sharon; Gaudio, Eugenio; Franchitto, Antonio; Mancinelli, Romina; Venter, Julie; Kopriva, Shelley; Ueno, Yoshiyuki; Alvaro, Domenico; Savage, Jennifer; Alpini, Gianfranco; Francis, Heather

2011-01-01

34

Selective inhibition of HDAC8 decreases neuroblastoma growth in vitro and in vivo and enhances retinoic acid-mediated differentiation.  

PubMed

For differentiation-defective malignancies, compounds that modulate transcription, such as retinoic acid and histone deacetylase (HDAC) inhibitors, are of particular interest. HDAC inhibitors are currently under investigation for the treatment of a broad spectrum of cancer diseases. However, one clinical drawback is class-specific toxicity of unselective inhibitors, limiting their full anticancer potential. Selective targeting of individual HDAC isozymes in defined tumor entities may therefore be an attractive alternative treatment approach. We have previously identified HDAC family member 8 (HDAC8) as a novel target in childhood neuroblastoma. Using small-molecule inhibitors, we now demonstrate that selective inhibition of HDAC8 exhibits antineuroblastoma activity without toxicity in two xenograft mouse models of MYCN oncogene-amplified neuroblastoma. In contrast, the unselective HDAC inhibitor vorinostat was more toxic in the same models. HDAC8-selective inhibition induced cell cycle arrest and differentiation in vitro and in vivo. Upon combination with retinoic acid, differentiation was significantly enhanced, as demonstrated by elongated neurofilament-positive neurites and upregulation of NTRK1. Additionally, MYCN oncogene expression was downregulated in vitro and tumor cell growth was markedly reduced in vivo. Mechanistic studies suggest that cAMP-response element-binding protein (CREB) links HDAC8- and retinoic acid-mediated gene transcription. In conclusion, HDAC-selective targeting can be effective in tumors exhibiting HDAC isozyme-dependent tumor growth in vivo and can be combined with differentiation-inducing agents. PMID:25695609

Rettig, I; Koeneke, E; Trippel, F; Mueller, W C; Burhenne, J; Kopp-Schneider, A; Fabian, J; Schober, A; Fernekorn, U; von Deimling, A; Deubzer, H E; Milde, T; Witt, O; Oehme, I

2015-01-01

35

Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth.  

PubMed

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with a hypercatabolic condition. Plasma levels of classical hormones and humoral mediators (prostaglandin E2 and tumor necrosis factor-alpha) are early perturbed after tumor transplantation (Tessitore, L., Costelli, P. and Baccino, F.M. (1993) Humoral mediation for cachexia in tumour-bearing rats. Br. J. Cancer, 67, 16-23). Enhanced protein degradation rates and alteration of lipoprotein lipase activity mainly account for the wasting of protein and adipose mass, respectively. However, the daily intragastric administration of eicosapentaenoic acid (1.5 g/kg body wt) to AH-130 bearing rats was completely ineffective either in preventing tissue waste or in reducing tumor growth. The low degree of differentiation and the high growth rate of the AH0130 hepatoma probably account for this lack of effect. PMID:7585474

Costelli, P; Llovera, M; López-Soriano, J; Carbó, N; Tessitore, L; López-Soriano, F J; Baccino, F M; Argilés, J M

1995-10-20

36

All-trans- and 9-cis-retinoic acid inhibit growth of normal human and murine B cell precursors.  

PubMed

In the present paper we demonstrate that physiologic levels (10 nM) of both all-trans- and 9-cis-retinoic acid (RA) are potent inhibitors of the growth of human as well as murine B cell precursors in vitro. Ten nanomolar concentrations of all-trans- and 9-cis-RA reduced the DNA synthesis ([3H]thymidine uptake) of human B cell precursors (CD19+ IgM-) stimulated with O-tetradecanoylphorbol-13-acetate and ionomycin by approximately 55% and 70%, respectively. Human B cell precursors stimulated with low m.w. B cell growth factor were also inhibited by RA. Ten nanomolar concentrations of either isoform of RA reduced DNA synthesis by approximately 50%. No effect of RA on differentiation to sIgM positive cells was noted. The potent growth-inhibiting effect of RA on human B cell precursors was confirmed in the murine cell system. B lymphopoiesis from murine hematopoietic precursors (Lin-B220(+)-containing cells) was induced by stimulation with IL-7. Concentrations of all-trans- and 9-cis-RA as low as 10 pM reduced the colony-forming ability of the IL-7-stimulated Lin-B220(+)-containing cells. Ten nanomolar concentrations of either isoform reduced colony formation by approximately 60%. RA was not toxic to the cells, as the inhibition of colony formation after 24 h was reversible at concentrations as high as 1 microM. The growth-inhibiting effect of RA was directly mediated, as revealed by single cell analysis of the Lin-B220(+)-containing cells. Thus, vitamin A appears to have an important role in regulation of B lymphopoiesis. PMID:7602122

Fahlman, C; Jacobsen, S E; Smeland, E B; Lømo, J; Naess, C E; Funderud, S; Blomhoff, H K

1995-07-01

37

Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth of Mycobacterium tuberculosis  

SciTech Connect

The remarkable survival ability of Mycobacterium tuberculosis in infected hosts is related to the presence of cell wall-associated mycolic acids. Despite their importance, the mechanisms that modulate expression of these lipids in response to environmental changes are unknown. Here we demonstrate that the enoyl-ACP reductase activity of InhA, an essential enzyme of the mycolic acid biosynthetic pathway and the primary target of the anti-tubercular drug isoniazid, is controlled via phosphorylation. Thr-266 is the unique kinase phosphoacceptor, both in vitro and in vivo. The physiological relevance of Thr-266 phosphorylation was demonstrated using inhA phosphoablative (T266A) or phosphomimetic (T266D/E) mutants. Enoyl reductase activity was severely impaired in the mimetic mutants in vitro, as a consequence of a reduced binding affinity to NADH. Importantly, introduction of inhA{_}T266D/E failed to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment. This study suggests that phosphorylation of InhA may represent an unusual mechanism that allows M. tuberculosis to regulate its mycolic acid content, thus offering a new approach to future anti-tuberculosis drug development.

Molle, Virginie; Gulten, Gulcin; Vilchèze, Catherine; Veyron-Churlet, Romain; Zanella-Cléon, Isabelle; Sacchettini, James C.; Jacobs, Jr, William R.; Kremer, Laurent (CNRS-UMR); (Einstein); (TAM)

2011-08-24

38

Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis.  

PubMed

The role of angiogenesis in tumor growth and metastasis is well established. Identification of a small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we showed that acetyl-11-keto-beta-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg AKBA) after solid tumors reached approximately 100 mm(3) (n = 5). The inhibitory effect of AKBA on tumor growth was well correlated with suppression of angiogenesis. When examined for the molecular mechanism, we found that AKBA significantly inhibited blood vessel formation in the Matrigel plug assay in mice and effectively suppressed vascular endothelial growth factor (VEGF)-induced microvessel sprouting in rat aortic ring assay ex vivo. Furthermore, AKBA inhibited VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures from primary cultured human umbilical vascular endothelial cells in a dose-dependent manner. Western blot analysis and in vitro kinase assay revealed that AKBA suppressed VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2) kinase (KDR/Flk-1) with IC(50) of 1.68 micromol/L. Specifically, AKBA suppressed the downstream protein kinases of VEGFR2, including Src family kinase, focal adhesion kinase, extracellular signal-related kinase, AKT, mammalian target of rapamycin, and ribosomal protein S6 kinase. Our findings suggest that AKBA potently inhibits human prostate tumor growth through inhibition of angiogenesis induced by VEGFR2 signaling pathways. PMID:19567671

Pang, Xiufeng; Yi, Zhengfang; Zhang, Xiaoli; Sung, Bokyung; Qu, Weijing; Lian, Xiaoyuan; Aggarwal, Bharat B; Liu, Mingyao

2009-07-15

39

Tetra-O-methyl nordihydroguaiaretic acid induces growth arrest and cellular apoptosis by inhibiting Cdc2 and survivin expression.  

PubMed

We previously reported that Sp1-dependent Cdc2 gene expression is inhibited by tetra-O-methyl nordihydroguaiaretic acid (M(4)N) and that M(4)N is likely responsible for causing growth arrest in M(4)N-treated transformed C3 cells. Here, we show that after M(4)N treatment and cell-cycle arrest, expression of the Sp1-dependent survivin gene, a member of the inhibitor of apoptosis family, is also suppressed, and the mitochondrial apoptotic pathway is activated. To confirm that inhibition of Cdc2 and survivin gene expression is necessary for M(4)N-induced growth arrest and apoptosis, we tested the effect of adding Cdc2 and survivin back to M(4)N-treated cells. Cell division was transiently restored in the presence of M(4)N after transfection of an exogenous Cdc2 gene copy under the control of the Sp1-independent cytomegalovirus promoter. Caspase-3 activation was also reduced by 50% and 75% in transiently and stably survivin-transfected C3 cells, respectively. The results suggest that M(4)N induces growth arrest and apoptosis by suppressing Cdc2 and survivin expression, which constitutes the cellular basis of its antitumoric action. PMID:15329416

Chang, Chih-Chuan; Heller, Jonathan D; Kuo, Jennifer; Huang, Ru Chih C

2004-09-01

40

Tetra-O-methyl nordihydroguaiaretic acid induces growth arrest and cellular apoptosis by inhibiting Cdc2 and survivin expression  

PubMed Central

We previously reported that Sp1-dependent Cdc2 gene expression is inhibited by tetra-O-methyl nordihydroguaiaretic acid (M4N) and that M4N is likely responsible for causing growth arrest in M4N-treated transformed C3 cells. Here, we show that after M4N treatment and cell-cycle arrest, expression of the Sp1-dependent survivin gene, a member of the inhibitor of apoptosis family, is also suppressed, and the mitochondrial apoptotic pathway is activated. To confirm that inhibition of Cdc2 and survivin gene expression is necessary for M4N-induced growth arrest and apoptosis, we tested the effect of adding Cdc2 and survivin back to M4N-treated cells. Cell division was transiently restored in the presence of M4N after transfection of an exogenous Cdc2 gene copy under the control of the Sp1-independent cytomegalovirus promoter. Caspase-3 activation was also reduced by 50% and 75% in transiently and stably survivin-transfected C3 cells, respectively. The results suggest that M4N induces growth arrest and apoptosis by suppressing Cdc2 and survivin expression, which constitutes the cellular basis of its antitumoric action. PMID:15329416

Chang, Chih-Chuan; Heller, Jonathan D.; Kuo, Jennifer; Huang, Ru Chih C.

2004-01-01

41

Okadaic acid inhibits cell growth and photosynthetic electron transport in the alga Dunaliella tertiolecta.  

PubMed

Okadaic acid (OA), which is produced by several dinoflagellate species, is a phycotoxin known to induce a decrease of biomass production in phytoplankton. However, the mechanisms of OA cytotoxicity are still unknown in microalgae. In this study, we exposed the green microalga Dunaliella tertiolecta to OA concentrations of 0.05 to 0.5 ?M in order to evaluate its effects on cell division, reactive oxygen species production and photosynthetic electron transport. After 72 h of treatment under continuous illumination, OA concentrations higher than 0.10 ?M decreased culture cell density, induced oxidative stress and inhibited photosystem II electron transport capacity. OA effect in D. tertiolecta was strongly light dependent since no oxidative stress was observed when D. tertiolecta was exposed to OA in the dark. In the absence of light, the effect of OA on culture cell density and photosystem II activity was also significantly reduced. Therefore, light appears to have a significant role in the toxicity of OA in microalgae. Our results indicate that the site of OA interaction on photosynthetic electron transport is likely to be at the level of the plastoquinone pool, which can lead to photo-oxidative stress when light absorbed by the light-harvesting complex of photosystem II cannot be dissipated via photochemical pathways. These findings allowed for a better understanding of the mechanisms of OA toxicity in microalgae. PMID:22134032

Perreault, François; Matias, Marcelo Seleme; Oukarroum, Abdallah; Matias, William Gerson; Popovic, Radovan

2012-01-01

42

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

PubMed

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

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

2010-03-01

43

Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase.  

PubMed

Resveratrol is a natural polyphenolic compound and has been shown to exhibit cardio-protective as well as anti-neoplastic effects on various types of cancers. However, the exact mechanism of its anti-tumor effect is not clearly defined. Resveratrol has been shown to have strong hypolipidemic effect on normal adipocytes and as hyper-lipogenesis is a hallmark of cancer cell physiology, the effect of resveratrol on lipid synthesis in cancer stem-like cells (CD24(-)/CD44(+)/ESA(+)) that were isolated from both ER+ and ER- breast cancer cell lines was examined. The authors found that resveratrol significantly reduced the cell viability and mammosphere formation followed by inducing apoptosis in cancer stem-like cells. This inhibitory effect of resveratrol is accompanied by a significant reduction in lipid synthesis which is caused by the down-regulation of the fatty acid synthase (FAS) gene followed by up-regulation of pro-apoptotic genes, DAPK2 and BNIP3. The activation of apoptotic pathway in the cancer stem-like cells was suppressed by TOFA and by Fumonisin B1, suggesting that resveratrol-induced apoptosis is indeed through the modulation of FAS-mediated cell survival signaling. Importantly, resveratrol was able to significantly suppress the growth of cancer stem-like cells in an animal model of xenograft without showing apparental toxicity. Taken together, the results of this study indicate that resveratrol is capable of inducing apoptosis in the cancer stem-like cells through suppression of lipogenesis by modulating FAS expression, which highlights a novel mechanism of anti-tumor effect of resveratrol. PMID:21188630

Pandey, Puspa R; Okuda, Hiroshi; Watabe, Misako; Pai, Sudha K; Liu, Wen; Kobayashi, Aya; Xing, Fei; Fukuda, Koji; Hirota, Shigeru; Sugai, Tamotsu; Wakabayashi, Go; Koeda, Keisuke; Kashiwaba, Masahiro; Suzuki, Kazuyuki; Chiba, Toshimi; Endo, Masaki; Fujioka, Tomoaki; Tanji, Susumu; Mo, Yin-Yuan; Cao, Deliang; Wilber, Andrew C; Watabe, Kounosuke

2011-11-01

44

Caffeic acid phenethyl ester suppresses melanoma tumor growth by inhibiting PI3K/AKT/XIAP pathway  

PubMed Central

Melanoma is highly metastatic and resistant to chemotherapeutic drugs. Our previous studies have demonstrated that caffeic acid phenethyl ester (CAPE) suppresses the growth of melanoma cells and induces reactive oxygen species generation. However, the exact mechanism of the growth suppressive effects of CAPE was not clear. Here, we determined the potential mechanism of CAPE against melanoma in vivo and in vitro. Administration of 10 mg/kg/day CAPE substantially suppressed the growth of B16F0 tumor xenografts in C57BL/6 mice. Tumors from CAPE-treated mice showed reduced phosphorylation of phosphoinositide 3-kinase, AKT, mammalian target of rapamycin and protein level of X-linked inhibitor of apoptosis protein (XIAP) and enhanced the cleavage of caspase-3 and poly (ADP ribose) polymerase. In order to confirm the in vivo observations, melanoma cells were treated with CAPE. CAPE treatment suppressed the activating phosphorylation of phosphoinositide 3-kinase at Tyr 458, phosphoinositide-dependent kinase-1 at Ser 241, mammalian target of rapamycin at Ser 2448 and AKT at Ser 473 in B16F0 and SK-MEL-28 cells in a concentration and time-dependent study. Furthermore, the expression of XIAP, survivin and BCL-2 was downregulated by CAPE treatment in both cell lines. Significant apoptosis was observed by CAPE treatment as indicated by cleavage of caspase-3 and poly (ADP ribose) polymerase. AKT kinase activity was inhibited by CAPE in a concentration-dependent manner. CAPE treatment increased the nuclear translocation of XIAP, indicating increased apoptosis in melanoma cells. To confirm the involvement of reactive oxygen species in the inhibition of AKT/XIAP pathway, cells were treated with antioxidant N-acetyl-cysteine (NAC) prior to CAPE treatment. Our results indicate that NAC blocked CAPE-mediated AKT/XIAP inhibition and protected the cells from apoptosis. Because AKT regulates XIAP, their interaction was examined by immunoprecipitation studies. Our results show that CAPE treatment decreased the interaction of AKT with XIAP. To establish the involvement of AKT in the apoptosis-inducing effects of CAPE, cells were transfected with AKT. Our results revealed that AKT overexpression attenuated the decrease in XIAP and significantly blocked CAPE-mediated apoptosis. Similarly, overexpression of XIAP further decreased CAPE-induced apoptosis. Taken together, our results suggest that CAPE suppresses phosphoinositide 3-kinase/AKT/XIAP pathway leading to apoptosis in melanoma tumor cells in vitro and in vivo. PMID:23640046

Srivastava, Sanjay K.

2013-01-01

45

Orphan Receptor COUP-TF Is Required for Induction of Retinoic Acid Receptor ?, Growth Inhibition, and Apoptosis by Retinoic Acid in Cancer Cells  

PubMed Central

Retinoic acid receptor ? (RAR?) plays a critical role in mediating the anticancer effects of retinoids. Expression of RAR? is highly induced by retinoic acid (RA) through a RA response element (?RARE) that is activated by heterodimers of RARs and retinoid X receptors (RXRs). However, RAR? induction is often lost in cancer cells despite expression of RARs and RXRs. In this study, we provide evidence that orphan receptor COUP-TF is required for induction of RAR? expression, growth inhibition, and apoptosis by RA in cancer cells. Expression of COUP-TF correlates with RAR? induction in a variety of cancer cell lines. In addition, stable expression of COUP-TF in COUP-TF-negative cancer cells restores induction of RAR? expression, growth inhibition, and apoptosis by RA, whereas inhibition of COUP-TF by expression of COUP-TF antisense RNA represses the RA effects. In a transient transfection assay, COUP-TF strongly induced transcriptional activity of the RAR? promoter in a RA- and RAR?-dependent manner. By mutation analysis, we demonstrate that the effect of COUP-TF requires its binding to a DR-8 element present in the RAR? promoter. The binding of COUP-TF to the DR-8 element synergistically increases the RA-dependent RAR? transactivation function by enhancing the interaction of RAR? with its coactivator CREB binding protein. These results demonstrate that COUP-TF, by serving as an accessory protein for RAR? to induce RAR? expression, plays a critical role in regulating the anticancer activities of retinoids. PMID:10629053

Lin, Bingzhen; Chen, Guo-quan; Xiao, Dongmei; Kolluri, Siva Kumar; Cao, Xihua; Su, Hong; Zhang, Xiao-kun

2000-01-01

46

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

PubMed

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

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

2014-10-01

47

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

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.

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

48

Hyaluronic acid-paclitaxel conjugate inhibits growth of human squamous cell carcinomas of the head and neck via a hyaluronic acid-mediated mechanism.  

PubMed

Chemotherapeutic regimens incorporating taxanes significantly improve outcomes for patients with squamous cell carcinomas of the head and neck (SCCHN). However, treatment with taxanes is limited by toxicities, including bone marrow suppression and peripheral neuropathies. We proposed that conjugating taxanes to targeting carrier molecules would increase antitumor efficacy and decrease toxicity. The cell surface proteoglycan, CD44, is expressed on most SCCHNs, and we hypothesized that it is an attractive candidate for targeted therapy via its natural ligand, hyaluronic acid (HA). We determined whether HA-paclitaxel conjugates were able to decrease tumor growth and improve survival in orthotopic nude mouse human SCCHN xenograft models. HA-paclitaxel concentration-dependent growth inhibition of human SCCHN cell lines OSC-19 and HN5 in vitro, very similarly to free paclitaxel treatment. Tumor cell uptake of FITC-labeled HA-paclitaxel was significantly blocked with free HA, indicating the dependence of uptake on CD44. HA-paclitaxel administered intravenously once per week for three weeks at 120 mg/kg paclitaxel equivalents, far above the paclitaxel maximum tolerated dose, exerted superior tumor growth control to that of paclitaxel in both orthotopic OSC-19-luciferase and HN5 xenograft models in vivo. Mouse survival following HA-paclitaxel administration was prolonged compared with that of controls in mice implanted with either of these xenografts. Mice treated with HA-paclitaxel displayed increased TUNEL(+) cells in tumor tissue, as well as markedly reduced microvessel density compared to those treated with free paclitaxel. No acute histopathological changes were observed in mice treated with HA-paclitaxel. Thus, we conclude that HA-paclitaxel effectively inhibits tumor growth in human SCCHN xenografts via an HA-mediated mechanism and this conjugate should be considered for further preclinical development for this disease. PMID:21903450

Galer, Chad E; Sano, Daisuke; Ghosh, Sukhen C; Hah, Jeong H; Auzenne, Edmund; Hamir, Amirali N; Myers, Jeffrey N; Klostergaard, Jim

2011-11-01

49

Social stress promotes and ?-aminobutyric acid inhibits tumor growth in mouse models of non small cell lung cancer  

PubMed Central

Psychological distress is associated with increased lung cancer incidence and mortality. We have shown that non small cell lung cancer (NSCLC) cells in vitro are stimulated by the cAMP-dependent activation of CREB and ERK downstream of beta-adrenergic receptors and that this pathway is inhibited by the neurotransmitter ?-aminobutyric acid (GABA). Because the stress neurotransmitters noradrenalin and adrenaline are beta-adrenergic agonists, the current study has tested the hypothesis that social stress stimulates NSCLC growth in vivo and that GABA inhibits this effect. Social stress was induced in mice carrying xenografts from two NSCLC cell lines in the presence and absence of treatment with GABA. Xenograft sizes were measured after 30 days. Noradrenalin, adrenalin, cortisol, GABA and cAMP were measured in blood and tumor tissues by immunoassays. Expression of nicotinic receptors in the xenografts was assessed by real-time PCR and Western blotting. Protein expression of p-CREB, CREB, p-ERK, ERK and glutamate decarboxylase (GAD) 65 and 67 were determined by Western blotting. Xenograft sizes in stress-exposed mice were significantly increased. Nicotinic acetylcholine receptor (nAChR) subunits ?3, ?4, ?5, and ?7 in xenograft tissues showed posttranscriptional induction. Noradrenalin, adrenalin and cortisol were elevated in serum and xenograft tissue while GABA was suppressed. Levels of cAMP, p-CREB and p-ERK were increased while GAD 65 and GAD 67 were suppressed in tumor tissue. Treatment with GABA reversed the effects of stress. Our findings suggest that social stress stimulates NSCLC by increasing nAChR-mediated stress neurotransmitter signaling and that GABA is a promising novel agent for NSCLC intervention. PMID:21955519

Al-Wadei, Hussein A. N.; Plummer, Howard K.; Ullah, Mohammad F.; Unger, Benjamin; Brody, Joel R.; Schuller, Hildegard M.

2012-01-01

50

Upregulation of SOX9 inhibits the growth of human and mouse melanomas and restores their sensitivity to retinoic acid.  

PubMed

Treatments for primary and metastatic melanomas are rarely effective. Even therapeutics such as retinoic acid (RA) that are successfully used to treat several other forms of cancer are ineffective. Recent evidence indicates that the antiproliferative effects of RA are mediated by the transcription factor SOX9 in human cancer cell lines. As we have previously shown that SOX9 is expressed in normal melanocytes, here we investigated SOX9 expression and function in human melanomas. Although SOX9 was expressed in normal human skin, it was increasingly downregulated as melanocytes progressed to the premalignant and then the malignant and metastatic states. Overexpression of SOX9 in both human and mouse melanoma cell lines induced cell cycle arrest by increasing p21 transcription and restored sensitivity to RA by downregulating expression of PRAME, a melanoma antigen. Furthermore, SOX9 overexpression in melanoma cell lines inhibited tumorigenicity both in mice and in a human ex vivo model of melanoma. Treatment of melanoma cell lines with PGD2 increased SOX9 expression and restored sensitivity to RA. Thus, combined treatment with PGD2 and RA substantially decreased tumor growth in human ex vivo and mouse in vivo models of melanoma. The results of our experiments targeting SOX9 provide insight into the pathophysiology of melanoma. Further, the effects of SOX9 on melanoma cell proliferation and RA sensitivity suggest the encouraging possibility of a noncytotoxic approach to the treatment of melanoma. PMID:19273910

Passeron, Thierry; Valencia, Julio C; Namiki, Takeshi; Vieira, Wilfred D; Passeron, Hélène; Miyamura, Yoshinori; Hearing, Vincent J

2009-04-01

51

Deoxycholic acid inhibits the growth of BGC-823 gastric carcinoma cells via a p53?mediated pathway.  

PubMed

The aim of the present study was to investigate the effects of deoxycholic acid (DCA) on BGC?823 human gastric carcinoma cells and to explore the possible mechanisms underlying any such effects. Cell proliferation was detected using a 3?(4,5?Dimethylthiazol?2?yl)?2,5?diphenyl tetrazolium bromide assay, cell morphology was observed by inverted microscopy, and cell cycle progression and the mitochondrial membrane potential were analyzed using flow cytometry. The expression of Bcl?2, Bax, p53, Cyclin D1 and cyclin?dependent kinase (CDK)2 proteins in BGC?823 cells was analyzed with western blotting. The results demonstrated that DCA significantly inhibited cell growth, and that the cell cycle was arrested at the G1 phase. DCA was also shown to induce BGC?823 cell apoptosis, which was associated with the collapse of the mitochondrial membrane potential. The mitochondria?dependent pathway was activated via an increase in the ratio of Bax:Bcl?2 in BGC?823 cells. In addition, the expression of p53, cyclin D1 and CDK2 was altered following DCA treatment. These results suggest that DCA induces apoptosis in gastric carcinoma cells through activation of an intrinsic mitochondrial?dependent pathway, in which p53 is involved. PMID:25434397

Yang, Hai-Bo; Song, Wei; Cheng, Mei-Die; Fan, Hai-Fang; Gu, Xu; Qiao, Ying; Lu, Xin; Yu, Rui-He; Chen, Lan-Ying

2014-11-26

52

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

PubMed Central

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

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

2014-01-01

53

Elucidation of the mechanism of lactic acid growth inhibition and production in batch cultures of Lactobacillus rhamnosus  

Microsoft Academic Search

Batch cultures of Lactobacillus rhamnosus were carried out at different pH values in order to study the limitation of growth and lactic acid production by the hydrogen\\u000a ion, non-dissociated lactic acid and internal lactate concentrations. The effect of pH between 5 and 6.8 was studied at non-limiting\\u000a concentrations of glucose; this is more significant for the lactic acid fermentation rate

L. M. D. Gonçalves; A. Ramos; J. S. Almeida; A. M. R. B. Xavier; M. J. T. Carrondo

1997-01-01

54

Ursolic acid-induced AMP-activated protein kinase (AMPK) activation contributes to growth inhibition and apoptosis in human bladder cancer T24 cells.  

PubMed

Ursolic acid (UA) has shown the anti-tumor properties against a number of human cancers both in vivo and in vitro, however, its effect in bladder cancer and the corresponding mechanisms of action remain largely unknown. Here we found that UA dose-dependently induced growth inhibition and apoptosis in human bladder cancer T24 cells, and activation of AMP-activated protein kinase (AMPK) may contribute to the process. Our Western-blot results demonstrated a significant AMPK activation after UA treatment in T24 cells. Notably, knockdown of AMPK? by the targeted shRNA largely inhibited UA-induced T24 cell growth inhibition and apoptosis, while an AMPK activator 5-aminoimidazole-4-carboxamide-1-?-D-ribofuranoside (AICAR) or a constitutively active form of AMPK mimic UA's effect. We found the ceramide level was increased after UA treatment in T24 cells, and UA-induced AMPK activation and T24 cell apoptosis were inhibited by ceramide synthase inhibitor fumonisin B1, and was enhanced by exogenously adding cell permeable short-chain ceramide (C6), suggesting that ceramide might serve as an upstream signal for AMPK activation. Further, activation of AMPK by UA promoted c-Jun N-terminal kinase (JNK) activation, but inhibited mTOR complex 1 (mTORC1) signaling to cause survivin down-regulation. Our study suggests that activation of AMPK by UA contributes to growth inhibition and apoptosis in human bladder cancer cells. PMID:22387548

Zheng, Qing-you; Jin, Feng-suo; Yao, Chen; Zhang, Tong; Zhang, Guo-hui; Ai, Xing

2012-03-23

55

Growth Inhibition by Caffeic Acid, One of the Phenolic Constituents of Honey, in HCT 15 Colon Cancer Cells  

PubMed Central

Previous work from our laboratory showed that the mechanism of crude-honey induced apoptosis in colon cancer cells. Since phenolic constituents of honey were attributed to its apoptosis-inducing ability, we studied caffeic acid, one of the phenolic constituents of honey, induced effect on colon cancer cells. Antiproliferative effect of caffeic acid was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. MTT assay signified the antiproliferative nature of caffeic acid against the HCT 15 colon cancer cells. A time-dependent inhibition of colony formation was evident with caffeic acid treatment. Cell-cycle analysis of caffeic acid- (CA-) treated cells indicated increasing accumulation of cells at sub-G1 phase. Photomicrograph images of treated cells showed membrane blebbing and cell shrinkage. Yo-pro-1 staining of caffeic-acid-treated cells confirmed apoptosis in dose- and time-dependent manner. Increasing ROS generation and reduction in the mitochondrial membrane potential were also accompanied in the caffeic acid-induced apoptosis. This work will promote caffeic acid as a likely candidate in the chemoprevention of colon cancer. PMID:22649289

Jaganathan, Saravana Kumar

2012-01-01

56

Mead acid inhibits the growth of KPL-1 human breast cancer cells in vitro and in vivo.  

PubMed

The effects of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of breast cancer cell growth and metastasis were examined in vitro and in vivo by using the KPL-1 human breast cancer cell line. MA suppressed KPL-1 cell growth in culture with an IC50 value of 214.2 µM (65.7 µg/ml) for 72 h, and MA significantly suppressed transplanted KPL-1 tumor growth (tumor volume and tumor weight: 872±103 mm3 and 1,000±116 mg vs. 376±66 mm3 and 517±84 mg) and regional (axillary) lymph node metastasis (67%, 10/15 vs. 10%, 1/10) in female athymic mice fed an MA-rich diet for 8 weeks. Tumor suppression was due to the suppression of cell proliferation. In ELISA, although vascular endothelial growth factor (VEGF) levels were unchanged, VEGF receptor (VEGFR)1 and VEGFR2 levels were significantly decreased after treatment with a 214.2-µM dose of MA for 72 h; E-cadherin levels were unchanged. As VEGF, VEGFR1 and VEGFR2 expression was co-localized in KPL-1 cells, the mechanism leading to cell growth suppression was VEGF signaling directly to KPL-1 cells by an autocrine process. In contrast, MA did not influence angiogenesis. The mechanisms of action were through VEGF signaling directly to cancer cells. PMID:25109488

Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Hamazaki, Kei; Emoto, Yuko; Yuri, Takashi; Yuki, Michiko; Shikata, Nobuaki; Kawashima, Hiroshi; Tsubura, Airo

2014-10-01

57

Ursolic acid inhibited growth of hepatocellular carcinoma HepG2 cells through AMPK?-mediated reduction of DNA methyltransferase 1.  

PubMed

Hepatocellular carcinoma (HCC), the major histological subtype of primary liver cancer, remains one of the most common malignancies worldwide. Due to the complicated pathogenesis of this malignancy, the outcome for comprehensive treatment is limited. Chinese herbal medicine (CHM) is emerging as a promising choice for its multi-targets and coordinated intervention effects against HCC. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid found in CHM, exerts anti-tumor effects and is emerging as an effective compound for cancer prevention and therapy. However, the molecular mechanisms underlying the action of UA remain largely unknown. In this study, we showed that UA inhibited the growth of HCC cells and induced apoptosis in the dose- and time-dependent fashion. Furthermore, we found that UA induced phosphorylation of AMP-activated protein kinase alpha (AMPK?) and suppressed the protein expression of DNA methyltransferase 1 (DNMT1) in the dose-dependent manner. The inhibitor of AMPK, compound C blocked, while an activator of AMPK, metformin augmented the effect of UA on DNMT1 expression. In addition, UA suppressed the expression of transcription factor Sp1. Conversely, overexpression of Sp1 reversed the effect of UA on DNMT1 expression and cell growth. Collectively, our results show for the first time that UA inhibits growth of HCC through AMPK?-mediated inhibition of Sp1; this in turn results in inhibition of DNMT1. This study reveals a potential novel mechanism by which UA controls growth of HCC cells and suggests that DNMT1 could be novel target for HCC chemoprevention and treatment. PMID:25547067

Yie, Yinyi; Zhao, Shunyu; Tang, Qin; Zheng, Fang; Wu, Jingjing; Yang, LiJuan; Deng, ShiGuan; Hann, Swei Sunny

2015-04-01

58

Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer  

SciTech Connect

Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2?-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E{sub 2} (PGE{sub 2}) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B{sub 4} (LTB{sub 4}). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser{sup 241}), phospho-Akt (Thr{sup 308}), phospho-Bad (Ser{sup 136}), and Bcl-x{sub L} expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE{sub 2}, LTB{sub 4} and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr{sup 308}). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. - Highlights: • Isoliquiritigenin induces growth inhibition and apoptosis in human breast cancer. • The proapoptotic action of isoliquiritigenin has been studied in vitro and in vivo. • Arachidonic acid metabolic network mediates isoliquiritigenin-induced apoptosis. • PI3K/Akt deactivation is asssociated with isoliquiritigenin-induced apoptosis. • Isoliquiritigenin may be a multi-target drug in the treatment of breast cancer.

Li, Ying; Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Wang, Yuzhong [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079 (China); Zheng, Hao; Yu, Wei; Chai, Hongyan [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390,USA (United States); Guo, Austin M. [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Yue, Jiang; Peng, Renxiu [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

2013-10-01

59

Short-Chain Fatty Acids Inhibit Growth Hormone and Prolactin Gene Transcription via cAMP/PKA/CREB Signaling Pathway in Dairy Cow Anterior Pituitary Cells  

PubMed Central

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

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

60

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

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

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

2015-02-01

61

Methylseleninic acid (MSA) inhibits 17?-estradiol-induced cell growth in breast cancer T47D cells via enhancement of the antioxidative thioredoxin/ thioredoxin reductase system.  

PubMed

The purpose of this study was to clarify the cell growth inhibitory mechanism of human breast cancer cells caused by selenium (Se) compounds. In the presence of 17?-estradiol (E(2)) at physiological concentrations, growth of estrogen receptor ? (ER?)-positive T47D cells was markedly inhibited by 1 × 10(-6) mol/L methylseleninic acid (MSA) with no Se related toxicity.Under conditions where cell growth was inhibited, MSA decreased ER? mRNA levels and subsequent protein levels; further decreasing expression of estrogen-responsive finger protein (Efp) which is a target gene product of ER? and promotes G2/M progression of the cell cycle. Therefore, the decline in Efp expression is presumed to be involved in G2 arrest. Coincidentally, the antioxidative thioredoxin/ thioredoxin reductase (Trx/TrxR) system in cells was enhanced by the synergistic action of E(2) and MSA. It has been reported that ROS-induced oxidative stress enhanced ER? expression. E(2) increased production of intracellular ROS in T47D cells. Meanwhile, MSA significantly decreased E(2)-induced ROS accumulation. From these results, activation of the Trx/TrxR system induced by the coexistence of MSA and E(2) suppresses oxidative stress and decreases expression of ER?, and finally induces the growth arrest of T47D cells through disruption of ER? signaling. PMID:22975630

Okuno, Tomofumi; Miura, Kiyoshi; Sakazaki, Fumitoshi; Nakamuro, Katsuhiko; Ueno, Hitoshi

2012-01-01

62

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

PubMed

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

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

2012-01-01

63

Boswellic acid inhibits growth and metastasis of human colorectal cancer in orthotopic mouse model by downregulating inflammatory, proliferative, invasive and angiogenic biomarkers.  

PubMed

Numerous cancer therapeutics were originally identified from natural products used in traditional medicine. One such agent is acetyl-11-keto-beta-boswellic acid (AKBA), derived from the gum resin of the Boswellia serrata known as Salai guggal or Indian frankincense. Traditionally, it has been used in Ayurvedic medicine to treat proinflammatory conditions. In this report, we hypothesized that AKBA can affect the growth and metastasis of colorectal cancer (CRC) in orthotopically implanted tumors in nude mice. We found that the oral administration of AKBA (50-200 mg/kg) dose-dependently inhibited the growth of CRC tumors in mice, resulting in decrease in tumor volumes than those seen in vehicle-treated mice without significant decreases in body weight. In addition, we observed that AKBA was highly effective in suppressing ascites and distant metastasis to the liver, lungs and spleen in orthotopically implanted tumors in nude mice. When examined for the mechanism, we found that markers of tumor proliferation index Ki-67 and the microvessel density cluster of differentiation (CD31) were significantly downregulated by AKBA treatment. We also found that AKBA significantly suppressed nuclear factor-?B (NF-?B) activation in the tumor tissue and expression of proinflammatory (cyclooxygenase-2), tumor survival (bcl-2, bcl-xL, inhibitor of apoptosis (IAP-1) and survivin), proliferative (cyclin D1), invasive (intercellular adhesion molecule 1 and matrix metalloproteinase-9) and angiogenic C-X-C (CXC) receptor 4 and vascular endothelial growth factor) biomarkers. When examined for serum and tissue levels of AKBA, a dose-dependent increase in the levels of the drug was detected, indicating its bioavailability. Thus, our findings suggest that this boswellic acid analog can inhibit the growth and metastasis of human CRC in vivo through downregulation of cancer-associated biomarkers. PMID:21702037

Yadav, Vivek R; Prasad, Sahdeo; Sung, Bokyung; Gelovani, Juri G; Guha, Sushovan; Krishnan, Sunil; Aggarwal, Bharat B

2012-05-01

64

Acid precipitation and food quality: Inhibition of growth and survival in black ducks and mallards by dietary aluminum, calcium and phosphorus  

USGS Publications Warehouse

In areas impacted by acid precipitation, water chemistry of acidic ponds and streams often changes, resulting in increased mobilization of aluminum and decreased concentration of calcium carbonate. Aluminum binds with phosphorus and inhibits its uptake by organisms. Thus, invertebrate food organisms used by waterfowl may have inadequate Ca and P or elevated Al for normal growth and development. Acid rain and its effects may be one of the factors negatively impacting American black ducks (Anas rubripes) in eastern North America. One-day old mallards (A. platyrhynchos) and black ducks were placed on one of three Ca:P regimens: low:low (LL), normal:normal (NN), and low:high (LH) with each regimen divided further into three or four Al levels for 10 weeks. Forty-five % of the black ducks died on nine different diets whereas only 28% of the mallards died on three different diets. Mortality was significantly related to diet in both species. Growth rates for body weight, culmens, wings, and tarsi of both species on control diets exceeded those on many treatment diets but the differences were less apparent for mallards than for black ducks. Differences among treatments were due to both Ca:P and Al levels.

Sparling, D.W.

1990-01-01

65

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

SciTech Connect

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.

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

66

Caffeic Acid Derivatives Inhibit the Growth of Colon Cancer: Involvement of the PI3-K/Akt and AMPK Signaling Pathways  

PubMed Central

Background The aberrant regulation of phosphatidylinositide 3-kinases (PI3-K)/Akt, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (m-TOR) signaling pathways in cancer has prompted significant interest in the suppression of these pathways to treat cancer. Caffeic acid (CA) has been reported to possess important anti-inflammatory actions. However, the molecular mechanisms by which CA derivatives including caffeic acid phenethyl ester (CAPE) and caffeic acid phenylpropyl ester (CAPPE), exert inhibitory effects on the proliferation of human colorectal cancer (CRC) cells have yet to be elucidated. Methodology/Principal Findings CAPE and CAPPE were evaluated for their ability to modulate these signaling pathways and suppress the proliferation of CRC cells both in vitro and in vivo. Anti-cancer effects of these CA derivatives were measured by using proliferation assays, cell cycle analysis, western blotting assay, reporter gene assay and immunohistochemical (IHC) staining assays both in vitro and in vivo. This study demonstrates that CAPE and CAPPE exhibit a dose-dependent inhibition of proliferation and survival of CRC cells through the induction of G0/G1 cell cycle arrest and augmentation of apoptotic pathways. Consumption of CAPE and CAPPE significantly inhibited the growth of colorectal tumors in a mouse xenograft model. The mechanisms of action included a modulation of PI3-K/Akt, AMPK and m-TOR signaling cascades both in vitro and in vivo. In conclusion, the results demonstrate novel anti-cancer mechanisms of CA derivatives against the growth of human CRC cells. Conclusions CA derivatives are potent anti-cancer agents that augment AMPK activation and promote apoptosis in human CRC cells. The structure of CA derivatives can be used for the rational design of novel inhibitors that target human CRC cells. PMID:24960186

Kuo, Yueh-Hsiung; Pai, Man-Hui; Chiu, Hsi-Lin; Rodriguez, Raymond L.; Tang, Feng-Yao

2014-01-01

67

Boswellic Acid Inhibits Growth and Metastasis of Human Colorectal Cancer in Orthotopic Mouse Model By Downregulating Inflammatory, Proliferative, Invasive, and Angiogenic Biomarkers  

PubMed Central

Numerous cancer therapeutics were originally identified from natural products used in traditional medicine. One such agent is acetyl-11-keto-beta-boswellic acid (AKBA), derived from the gum resin of the Boswellia serrata known as Salai guggal or Indian frankincense. Traditionally it has been used in Ayurvedic medicine to treat proinflammatory conditions. In the present report, we hypothesized that AKBA can affect the growth and metastasis of colorectal cancer (CRC) in orthotopically-implanted tumors in nude mice. We found that the oral administration of AKBA (50-200 mg/kg) dose-dependently inhibited the growth of CRC tumors in mice, resulting in decrease in tumor volumes than those seen in vehicle-treated mice without significant decreases in body weight. In addition, we observed that AKBA was highly effective in suppressing ascites and distant metastasis to the liver, lungs, and spleen in orthotopically-implanted tumors in nude mice. When examined for the mechanism, we found that markers of tumor proliferation index Ki-67 and the microvessel density CD31; were significantly downregulated by AKBA treatment. We also found that AKBA significantly suppressed NF-?B activation in the tumor tissue and expression of pro-inflammatory (COX2), tumor survival (bcl-2, bcl-xL, IAP-1, survivin), proliferative (cyclin D1), invasive (ICAM-1, MMP-9) and angiogenic (CXCR4 and VEGF) biomarkers. When examined for serum and tissue levels of AKBA, a dose-dependent increase in the levels of the drug was detected, indicating its bioavailability. Thus, our findings suggest that this boswellic acid analogue can inhibit the growth and metastasis of human CRC in vivo through downregulation of cancer-associated biomarkers. PMID:21702037

Yadav, Vivek R.; Prasad, Sahdeo; Sung, Bokyung; Gelovani, Juri G.; Guha, Sushovan; Krishnan, Sunil; Aggarwal, Bharat B.

2011-01-01

68

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 Central

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 appears 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, -011, -013 and -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 to the single treatment regimens. A half dose of daily Sal-B (40mg/kg/day) and celecoxib (2.5mg/kg/day) significantly inhibited JHU-013 xenograft growth, relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was not only 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 of celecoxib hold potential as a new preventive strategy in targeting inflammatory associated tumor development. PMID:20501859

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

2010-01-01

69

tetra-O-methylnordihydroguaiaretic acid inhibits melanoma in vivo.  

PubMed

tetra-O-methylnordihydroguaiaretic acid is a derivative of a naturally-occurring lignan, nordihydroguaiaretic acid, that has previously been shown to inhibit various cancer types in vitro and in vivo. Additionally, nordihydroguaiaretic acid has been shown to have nephrotoxic effects in the rat. Here we show that tetra-O-methylnordihydroguaiaretic acid inhibits the growth of a number of tumor cell lines in vitro by inducing apoptosis in a non-schedule-dependent manner. Further, this compound inhibits the synthesis of DNA by melanoma cells and causes cell cycle arrest in G0/G1 and G2/M phases of the cell cycle. tetra-O-Methylnordihydroguaiaretic acid also inhibits the growth of both murine and human melanomas and human colon cancer in vivo without apparent hepatic or renal toxicity. PMID:11485827

Lambert, J D; Meyers, R O; Timmermann, B N; Dorr, R T

2001-09-28

70

Antisense Growth Inhibition of Methicillin-Resistant Staphylococcus aureus by Locked Nucleic Acid Conjugated with Cell-Penetrating Peptide as a Novel FtsZ Inhibitor.  

PubMed

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

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

71

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

PubMed

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

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

2014-11-16

72

High concentrations of L-ascorbic acid specifically inhibit the growth of human leukemic cells via downregulation of HIF-1? transcription.  

PubMed

We examined the antileukemic effects of high concentrations of L-ascorbic acid (high AA) on human leukemic cells. In vitro, high AA markedly induced apoptosis in various leukemic cell lines by generating hydrogen peroxide (H2O2) but not in normal hematopoietic stem/progenitor cells. High AA significantly repressed leukemic cell proliferation as well as neoangiogenesis in immunodeficient mice. We then noted that in leukemic cells, HIF-1? transcription was strongly suppressed by high AA and correlated with the transcription of VEGF. Our data indicate that exposure to high AA markedly increased the intracellular AA content of leukemic cells and inhibited the nuclear translocation of NF-?B, which mediates expression of HIF-1?. We next generated K562 cells that overexpressed HIF-1? (K562-HIF1? cells) and assessed the mechanistic relationship between inhibition of HIF-1? transcription and the antileukemic effect of high AA. The ability of high AA to induce apoptosis was significantly lower in K562-HIF1? cells than in K562 cells in vitro. We found that expression of HIF-1?-regulated antiapoptotic proteins of the Bcl-2 family, such as Mcl-1, Bcl-xL, and Bcl-2, was significantly suppressed by high AA in K562 cells, but was sustained at higher levels in K562-HIF1? cells, regardless of high AA exposure. Moreover, repression of cell proliferation and neoangiogenesis by high AA was completely abrogated in mice receiving transplants of K562-HIF1? cells. These results indicate that, along with H2O2 generation, downregulation of HIF-1? transcription plays a crucial role in growth inhibition of human leukemic cells by high AA. PMID:23626851

Kawada, Hiroshi; Kaneko, Mitsuyo; Sawanobori, Masakazu; Uno, Tomoko; Matsuzawa, Hideyuki; Nakamura, Yoshihiko; Matsushita, Hiromichi; Ando, Kiyoshi

2013-01-01

73

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

PubMed Central

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

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

74

Inhibition of gene expression and growth by antisense peptide nucleic acids in a multiresistant beta-lactamase-producing Klebsiella pneumoniae strain.  

PubMed

Klebsiella pneumoniae causes common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance. The emergence and spread of beta-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)(3)K peptide and investigated whether they could mediate gene-specific antisense effects in K. pneumoniae. No outer membrane permeabilization was observed with antisense PNAs when used alone. Antisense peptide-PNAs targeted at two essential genes, gyrA and ompA, were found to be growth inhibitory at concentrations of 20 muM and 40 muM, respectively. Mismatched antisense peptide-PNAs with sequence variations of the gyrA and ompA genes when used as controls were not growth inhibitory. Bactericidal effects exerted by peptide-anti-gyrA PNA and peptide-anti-ompA PNA on cells were observed within 6 h of treatment. The antisense peptide-PNAs specifically inhibited expression of DNA gyrase subunit A and OmpA from the respective targeted genes in a dose-dependent manner. Both antisense peptide-PNAs cured IMR90 cell cultures that were infected with K. pneumoniae (10(4) CFU) in a dose-dependent manner without any noticeable toxicity to the human cells. PMID:17158940

Kurupati, Prathiba; Tan, Kevin Shyong Wei; Kumarasinghe, Gamini; Poh, Chit Laa

2007-03-01

75

STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION  

PubMed Central

Somewhat discordant results which have been reported by others who have investigated the property of the whole blood of resistant animals to cause inhibition of growth or death of pneumococci have led us to investigate this matter and to develop a new technique in which the conditions as they are present in the animal body are more nearly imitated. The observations already made have rendered it probable that phagocytosis plays some rôle in any destructive power for pneumococcus which whole blood possesses. We have, therefore, employed mixtures of serum and leucocytes in our tests, since when blood is coagulated the conditions become highly artificial. Furthermore, in order to imitate more nearly the conditions in the circulating blood the mixtures have been constantly, though gently, agitated. For this purpose a specially devised apparatus has been employed. The mixtures of serum and leucocytes have been inoculated with varying numbers of pneumococci in the active growth phase and after varying intervals of time the tubes containing the mixtures of serum, leucocytes, and bacteria have been opened, examined microscopically, and cultures made. Employing this technique it has been found that the growth of pneumococci having low virulence for cats is markedly inhibited in mixtures of cat serum and cat leucocytes. It was impossible to recover pneumococci from the tubes showing no apparent growth, either when the contents were transplanted into various kinds of culture media, or when the contents were injected into mice of a variety highly susceptible to pneumococcus infection. 10,000 times the number of pneumococci sufficient ordinarily to kill a mouse failed to do so after a 24 hour sojourn in the cat serum-leucocyte mixture. Mixtures of dog serum and leucocytes exert a similar action. The serum and leucocytes of animals susceptible to pneumococcus infection (rabbits and guinea pigs,) on the other hand, failed to injure pneumococci even in extremely small quantities. These results indicate that the blood of resistant animals, at least of the dog and cat, possesses destructive properties for pneumococci, and that this destructive power is not possessed by the blood of certain susceptible animals. The experiments suggest that natural immunity depends chiefly, if not entirely, upon this property. The leucocytes play an active part in this process, but whether the destruction of the pneumococci occurs entirely within the leucocytes or not is not determined. That the serum also plays a part is shown by the fact that when the serum of resistant animals was inactivated before being used in the serum-leucocyte mixture, the growth of even very small numbers of pneumococci was not prevented. Further experiments with cat serum and leucocytes were carried out to determine the optimum rate and time of agitation, the amount of serum and leucocytes required, and also the period of incubation necessary for the inhibition of growth and death of the pneumococci to occur. PMID:19868840

Robertson, Oswald H.; Sia, Richard H. P.

1924-01-01

76

Predictive model for Clostridium perfringens growth in roast beef during cooling and inhibition of spore germination and outgrowth by organic acid salts.  

PubMed

Spores of foodborne pathogens can survive traditional thermal processing schedules used in the manufacturing of processed meat products. Heat-activated spores can germinate and grow to hazardous levels when these products are improperly chilled. Germination and outgrowth of Clostridium perfringens spores in roast beef during chilling was studied following simulated cooling schedules normally used in the processed-meat industry. Inhibitory effects of organic acid salts on germination and outgrowth of C. perfringens spores during chilling and the survival of vegetative cells and spores under abusive refrigerated storage was also evaluated. Beef top rounds were formulated to contain a marinade (finished product concentrations: 1% salt, 0.2% potassium tetrapyrophosphate, and 0.2% starch) and then ground and mixed with antimicrobials (sodium lactate and sodium lactate plus 2.5% sodium diacetate and buffered sodium citrate and buffered sodium citrate plus 1.3% sodium diacetate). The ground product was inoculated with a three-strain cocktail of C. perfringens spores (NCTC 8238, NCTC 8239, and ATCC 10388), mixed, vacuum packaged, heat shocked for 20 min at 75 degrees C, and chilled exponentially from 54.5 to 7.2 degrees C in 9, 12, 15, 18, or 21 h. C. perfringens populations (total and spore) were enumerated after heat shock, during chilling, and during storage for up to 60 days at 10 degrees C using tryptose-sulfite-cycloserine agar. C. perfringens spores were able to germinate and grow in roast beef (control, without any antimicrobials) from an initial population of ca. 3.1 log CFU/g by 2.00, 3.44, 4.04, 4.86, and 5.72 log CFU/g after 9, 12, 15, 18, and 21 h of exponential chilling. A predictive model was developed to describe sigmoidal C. perfringens growth curves during cooling of roast beef from 54.5 to 7.2 degrees C within 9, 12, 15, 18, and 21 h. Addition of antimicrobials prevented germination and outgrowth of C. perfringens regardless of the chill times. C. perfringens spores could be recovered from samples containing organic acid salts that were stored up to 60 days at 10 degrees C. Extension of chilling time to > or =9 h resulted in >1 log CFU/g growth of C. perfringens under anaerobic conditions in roast beef. Organic acid salts inhibited outgrowth of C. perfringens spores during chilling of roast beef when extended chill rates were followed. Although C. perfringens spore germination is inhibited by the antimicrobials, this inhibition may represent a hazard when such products are incorporated into new products, such as soups and chili, that do not contain these antimicrobials, thus allowing spore germination and outgrowth under conditions of temperature abuse. PMID:16355831

Sánchez-Plata, Marcos X; Amézquita, Alejandro; Blankenship, Erin; Burson, Dennis E; Juneja, Vijay; Thippareddi, Harshavardhan

2005-12-01

77

Targeting delivery of etoposide to inhibit the growth of human glioblastoma multiforme using lactoferrin- and folic acid-grafted poly(lactide-co-glycolide) nanoparticles.  

PubMed

Lactoferrin (Lf) and folic acid (FA) were crosslinked on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for transporting etoposide across the blood-brain barrier (BBB) and treating human brain malignant glioblastoma. Lf- and FA-grafted PLGA NPs (Lf/FA/PLGA NPs) were employed to permeate the monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes and to inhibit the multiplication of U87MG cells. Lf/FA/PLGA NPs showed a satisfactory entrapment efficiency of etoposide and characteristics of sustained drug release. When compared with PLGA NPs, the permeability coefficient for etoposide across the BBB using Lf/FA/PLGA NPs increased about twofold. The antiproliferative efficacy against the growth of U87MG cells was in the following order: Lf/FA/PLGA NPs>FA/PLGA NPs>PLGA NPs>free etoposide solution. In addition, the targeting ability of Lf/FA/PLGA NPs was evidenced by immunostaining of Lf receptor on HBMECs and folate receptor on U87MG cells during endocytosis. Lf/FA/PLGA NPs with loaded etoposide can be a promising anticancer pharmacotherapy to enhance the delivery of etoposide to malignant brain tumors for preclinical trials. PMID:25560309

Kuo, Yung-Chih; Chen, Yu-Chun

2015-02-01

78

Cell Growth Inhibition by Okadaic Acid Involves Gut-Enriched Kruppel-like Factor-Mediated Enhanced Expression of c-Myc  

Microsoft Academic Search

Human breast cancer (HBC) cell growth suppression by okadaic acid (OA) was previously found to involve elevated expression of oncogenes c-myc and c-fos and apoptosis. Since, c-Myc influences diverse pathways of cell growth, we hypoth- esized that elevated levels of c-Myc are involved in HBC growth suppression. Here, we investigated whether induction of c-Myc by OA or protein synthesis inhibitor

Liyue Zhang

79

Growth inhibition of Tax-activated human Jurkat leukemia T cells by all-trans retinoic acid requires JNK-1 inhibition.  

PubMed

Retinoids, including vitamin A (retinol) and its analogues, are critical for a variety of biological functions. In this study, we report that all-trans retinoic acid (ATRA) decreases Jun N-terminal kinase 1 (JNK-1) activity, antagonizing the effect of the Tax protein in Jurkat leukemia T cells transiently transfected for expressing the Tax protein. The Tax protein is one of the products of the human T-cell leukemia virus type 1 (HTLV-1) which is the etiologic agent of adult T-cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. The decrease in JNK-1 activity was followed by a marked decrease in the expression of interleukin (IL)-2 and a weak increase in interferon (IFN)-? in Jurkat cells treated with ATRA in a dose-dependent manner, suggesting a correlation between the expression of JNK-1 and the activity of the Tax protein. However, the expression levels of IL-4 and IL-10 were enhanced in cells transfected with Tax, compared with the levels in untransfected cells, but the expression levels were not affected following ATRA treatment. In transfection studies using a luciferase reporter construct expressing the IL-2 promoter or a tandem repeat of AP-1 or NF-?B, the inhibitory effect of ATRA on the IL-2 promoter and AP-1 construct was confirmed at the transcriptional level. However, the inhibitory effect in the NF-?B reporter construct was only marginal. In addition, our data demonstrated that JNK-1 is constitutively activated in Jurkat leukemia T cells expressing the Tax protein, suggesting that JNK-1 is required for Tax-induced proliferation of Jurkat leukemia cells. PMID:23129057

Parra, Eduardo; Gutiérrez, Luis

2013-01-01

80

Ascorbic acid inhibits the migration of walker 256 carcinosarcoma cells  

Microsoft Academic Search

The results of several experimental studies have shown that ascorbic acid inhibits tumor growth and metastasis. Ascorbic acid\\u000a is an antioxidant that acts as a scavenger for a wide range of reactive oxygen species (ROS). Both tumour metastasis and cell\\u000a migration have been correlated with the intracellular ROS level, so it was postulated that the inhibitory effect of ascorbic\\u000a acid

Ewa Wybieralska; Monika Koza; Jolanta Sroka; Jaros?aw Czy?; Zbigniew Madeja

2008-01-01

81

Inhibition and Facilitation of Nucleic Acid Amplification  

Microsoft Academic Search

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

IAN G. WILSON

1997-01-01

82

Growth-inhibiting conditions slow growth plate senescence.  

PubMed

The mammalian growth plate undergoes programmed senescence during juvenile life, causing skeletal growth to slow with age. We previously found that hypothyroidism in rats slowed both growth plate chondrocyte proliferation and growth plate senescence, suggesting that senescence is not dependent on age per se but rather on chondrocyte proliferation. However, one alternative explanation is that the observed slowing of growth plate senescence is a specific consequence of hypothyroidism. We reasoned that, if delayed senescence is a general consequence of growth inhibition, rather than a specific result of hypothyroidism, then senescence would also be slowed by other growth-inhibiting conditions. In this study, we therefore used tryptophan deficiency to temporarily inhibit growth in newborn rats for 4 weeks. We then allowed the animals to recover and studied the effects on growth plate senescence. We found that structural, functional, and molecular markers of growth plate senescence were delayed by prior tryptophan deficiency, indicating that the developmental program of senescence had occurred more slowly during the period of growth inhibition. Taken together with previous studies in hypothyroid rats, our findings support the hypothesis that delayed senescence is a general consequence of growth inhibition and hence that growth plate senescence is not simply a function of time per se but rather depends on growth. PMID:20974641

Forcinito, Patricia; Andrade, Anenisia C; Finkielstain, Gabriela P; Baron, Jeffrey; Nilsson, Ola; Lui, Julian C

2011-01-01

83

Growth inhibition of lettuce (Lactuca sativa L.) roots by ?-amino acids, 2-amino-3-cyclopropyl-butanoic acid and 2-amino-5-chloro-4-pentenoic acid, isolated from Amanita castanopsidis Hongo  

Microsoft Academic Search

The effect of two a-amino acids, 2-amino-3-cyclopropyl-butanoicacid (ACPBA) and 2-amino-5-chloro-4-pentenoic acid (ACPA) on the growth oflettuce (Lactuca sativa L.) roots was investigated. BothACPBA and ACPA at 10-4 significantly inhibitedgrowth of roots of light-grown seedlings, while they had no effect on hypocotylgrowth. The lengths of cortical cells in the mature region of roots that hadbeen exposed to either compound were significantly

Kazuyuki Wakabayashi; Kouichi Soga; Takayuki Hoson; Seiichiro Kamisaka; H. Yoshimura; K. Shibata

2001-01-01

84

Cyp26b1 Regulates Retinoic Acid-Dependent Signals in T Cells and Its Expression Is Inhibited by Transforming Growth Factor-?  

PubMed Central

Background The vitamin A metabolite, retinoic acid (RA), plays important roles in the regulation of lymphocyte properties. Dendritic cells in gut-related lymphoid organs can produce RA, thereby imprinting gut-homing specificity on T cells and enhancing transforming growth factor (TGF)-?-dependent induction of Foxp3+ regulatory T cells upon antigen presentation. In general, RA concentrations in cells and tissues are regulated by its degradation as well. However, it remained unclear if T cells could actively catabolize RA. Methodology/Principal Findings We assessed the expression of known RA-catabolizing enzymes in T cells from mouse lymphoid tissues. Antigen-experienced CD44+ T cells in gut-related lymphoid organs selectively expressed Cyp26b1, a member of the cytochrome P450 family 26. However, T cells in the spleen or skin-draining lymph nodes did not significantly express Cyp26b1. Accordingly, physiological levels of RA (1–10 nM) could induce Cyp26b1 expression in naïve T cells upon activation in vitro, but could not do so in the presence of TGF-?. Overexpression of Cyp26b1 significantly suppressed the RA effect to induce expression of the gut-homing receptor CCR9 on T cells. On the other hand, knocking down Cyp26b1 gene expression with small interfering RNA or inhibiting CYP26 enzymatic activity led to enhancement of the RA-induced CCR9 expression. Conclusions/Significance Our data demonstrate a role for CYP26B1 in regulating RA-dependent signals in activated T cells but not during TGF-?-dependent differentiation to Foxp3+ regulatory T cells. Aberrant expression of CYP26B1 may disturb T cell trafficking and differentiation in the gut and its related lymphoid organs. PMID:21249211

Takeuchi, Hajime; Yokota, Aya; Ohoka, Yoshiharu; Iwata, Makoto

2011-01-01

85

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

SciTech Connect

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.

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

86

Acidic Fibroblast Growth Factor Promotes Vascular Repair  

NASA Astrophysics Data System (ADS)

Intravascular injury to arteries can result in thickening of the intimal smooth muscle layer adjacent to the lumen by migration and proliferation of cells from the underlying medial smooth muscle layer accompanied by deposition of extracellular matrix. This pathological response, which decreases lumen diameter, might, in part, be the result of the access of smooth muscle cells to plasma and platelet-derived growth factors as a consequence of denudation of the overlying confluent monolayer of vascular endothelial cells. Injured rat carotid arteries were treated by i.v. administration of acidic fibroblast growth factor, a heparin-binding protein that is chemotactic and mitogenic for vascular endothelial cells. The growth factor treatment resulted in dose-dependent inhibition of intimal thickening with parallel promotion of endothelial regeneration over the injured area. Therefore, acidic fibroblast growth factor might be efficacious in the prevention of restenosis caused by intimal thickening following angioplasty in humans.

Bjornsson, Thorir D.; Dryjski, Maciej; Tluczek, John; Mennie, Robert; Ronan, John; Mellin, Theodore N.; Thomas, Kenneth A.

1991-10-01

87

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

PubMed Central

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

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

2014-01-01

88

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

Microsoft Academic Search

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

Otmar Spring; Achim Hager

1982-01-01

89

Inhibition of Aeromonas caviae and A. sobria by sodium choloride, citric acid, ascorbic acid, potassium sorbate and extracts of Thymus vulgaris.  

PubMed

The respective and combined effects of sodium chloride, ascorbic acid, citric acid, potassium sorbate, and Thymus vulgaris extract on the growth of Aeromonas caviae and Aeromonas sobria were investigated. Sodium chloride (3%) significantly reduced the growth and 4% NaCl inhibited growth of the tested strains. Ascorbic acid (0. 1%), potassium sorbate (0.05%), and citric acid (0.03%) slightly inhibited growth. T. vulgaris extract (0.3%) greatly reduced the growth. Various combinations of these compounds prevented growth of the tested strains. A combination of NaCl (3%) and ascorbic acid (0. 1%), citric acid (0.03%) and potassium sorbate (0.05%), or citric acid (0.03%) and ascorbic acid (0.1%) inhibited growth of A. caviae and A. sobria. In fish homogenates, the addition of ascorbic acid (0. 1%) and citric acid (0.03%) was the most effective combination tested. PMID:10957708

Abu-Ghazaleh, B M

2000-06-01

90

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

PubMed

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

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

2014-10-01

91

Two related cinnamic Acid derivatives from Brazilian honey bee propolis, baccharin and drupanin, induce growth inhibition in allografted sarcoma S-180 in mice.  

PubMed

Honey bee propolis is rich in cinnamic acid derivatives. Baccharin and drupanin from Brazilian honey bee propolis are cinnamic acid derivatives that contain prenyl moieties. We previously isolated these two compounds and demonstrated that they induce an apoptotic event in several tumor cell lines. In this study, we examined the tumoricidal activity of baccharin and drupanin in mice allografted with sarcoma S-180 and also studied the genotoxic effects on normal splenocytes using the alkaline single cell gel (comet) assay. We found that both baccharin and drupanin effectively suppressed growth of the tumor. Furthermore, these compounds induced a significant genotoxic effect on the tumor cells in comparison with normal splenocytes. Thus, baccharin and drupanin are potent tumor suppressive components of honeybee propolis. PMID:15930739

Mishima, Satoshi; Ono, Yosuke; Araki, Yoko; Akao, Yukihiro; Nozawa, Yoshinori

2005-06-01

92

Plant pathology Growth inhibition of Agaricus bisporus  

E-print Network

Plant pathology Growth inhibition of Agaricus bisporus and associated thermophilic species Agaricus bisporus and 3 isolates of thermophilic fungi active in mushroom composting. At concentrations compost I fungicide residue I Agaricus bisporus I Torula thermophila I Humicola grisea var ther- moidea

Paris-Sud XI, Université de

93

GROWTH INHIBITION BY SUBSTANCES IN LIVER  

PubMed Central

Certain tissue constituents inhibitory to cell growth, extracted from liver, are described. The findings indicate that inhibitory material is adsorbed to colloids in the native state and is freed from them by alcohol extraction. One inhibitor, ethanolamine, has been isolated. This substance differs in its biological properties from the bulk of the inhibitory material present in liver. Progress in purification of other inhibitors is described, and it is shown that inhibition by these extracts is not correlated with surface activity or with the presence of pigmented constituents. The inhibitors have common properties which suggest that they are of physiological significance in the regulation of growth: action over a wide range of concentrations at which other cell functions are undamaged; reversibility of action; presence in adult liver in concentrations near those which inhibit growth in vitro, while in embryo liver they are found only in much lower concentrations. PMID:19870972

Brues, Austin M.; Subbarow, Y.; Jackson, Elizabeth B.; Aub, Joseph C.

1940-01-01

94

Phytic Acid Inhibits Lipid Peroxidation In Vitro  

PubMed Central

Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation under in vitro and in vivo conditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100??M and 500??M effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II)/ascorbate. The observed inhibitory effect of PA on Fe(II)/ascorbate-induced lipid peroxidation was lower (10–20%) compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II)/ascorbate-induced peroxidation. In the absence of Fe(II)/ascorbate, PA at 100??M and 500??M significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100??M and 500??M) significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products. PMID:24260736

W?glarz, Ludmi?a; Dzier?ewicz, Zofia

2013-01-01

95

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

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

Bayan M. Abu-Ghazaleh

2006-01-01

96

Cimetidine inhibits angiogenesis and suppresses tumor growth.  

PubMed

Cimetidine, a histamine type-2 receptor antagonist, has been reported to improve survival of patients with cancers. However, the exact mechanisms by which cimetidine suppresses development of cancers remain to be elucidated. Solid tumors require neovascularization for their growth. Here, we investigated the effects of cimetidine on tumor growth and angiogenesis. Syngeneic colon cancer cells, CMT93 cells, were inoculated into the subcutaneous space of C57BL/6 mice. Mice were treated with either saline or cimetidine. Tumor size was measured everyday and angiogenesis was evaluated histologically. Cimetidine markedly suppressed tumor growth with reduced neovascularization in the tumor. Cimetidine had no effect on proliferation of CMT93 cells in vitro. Vascular endothelial growth factor production by cancer cells was not affected by cimetidine, while vascular-like tube formation by endothelial cells in vitro was significantly impaired in the presence of cimetidine. Our findings suggest that cimetidine suppresses tumor growth, at least in part, by inhibiting tumor-associated angiogenesis. PMID:15740937

Natori, Takeshi; Sata, Masataka; Nagai, Ryozo; Makuuchi, Masatoshi

2005-01-01

97

Bacterial contact-dependent growth inhibition (CDI)  

PubMed Central

Bacteria cooperate to form multicellular communities and compete against one another for environmental resources. Here, we review recent advances in our understanding of bacterial competition mediated by contact-dependent growth inhibition (CDI) systems. Different CDI+ bacteria deploy a variety of toxins to inhibit neighboring cells and protect themselves from autoinhibition by producing specific immunity proteins. The genes encoding CDI toxin–immunity pairs appear to be exchanged between cdi loci and are often associated with other toxin-delivery systems in diverse bacteria. CDI also appears to facilitate cooperative behavior between kin, suggesting that these systems may have other roles beyond competition. PMID:23473845

Ruhe, Zachary C.; Low, David A.; Hayes, Christopher S.

2013-01-01

98

Bacterial contact-dependent growth inhibition.  

PubMed

Bacteria cooperate to form multicellular communities and compete against one another for environmental resources. Here, we review recent advances in the understanding of bacterial competition mediated by contact-dependent growth inhibition (CDI) systems. Different CDI+ bacteria deploy a variety of toxins to inhibit neighboring cells and protect themselves from autoinhibition by producing specific immunity proteins. The genes encoding CDI toxin-immunity protein pairs appear to be exchanged between cdi loci and are often associated with other toxin-delivery systems in diverse bacterial species. CDI also appears to facilitate cooperative behavior between kin, suggesting that these systems may have other roles beyond competition. PMID:23473845

Ruhe, Zachary C; Low, David A; Hayes, Christopher S

2013-05-01

99

Menaquinone Analogs Inhibit Growth of Bacterial Pathogens  

PubMed Central

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

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

100

Ormeloxifene efficiently inhibits ovarian cancer growth.  

PubMed

Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials. Therefore, we examined whether ormeloxifene (ORM), a non-steroidal Selective Estrogen Receptor Modulator (SERM) currently used for contraception, is therapeutically effective at inhibiting ovarian cancer growth. We report that ORM treatment inhibits cell growth and induces apoptosis in ovarian cancer cell lines, including cell lines resistant to cisplatin. Furthermore, ORM treatment decreases Akt phosphorylation, increases p53 phosphorylation, and modulates the expression and localization patterns of p27, cyclin E, cyclin D1, and CDK2. In a pre-clinical xenograft mouse ORM treatment significantly reduces tumorigenesis and metastasis. These results indicate that ORM effectively inhibits the growth of cisplatin resistant ovarian cancer cells. ORM is currently in human use and has an established record of patient safety. Our encouraging in vitro and pre-clinical in vivo findings indicate that ORM is a promising candidate for the treatment of ovarian cancer. PMID:25306892

Maher, Diane M; Khan, Sheema; Nordquist, Jordan L; Ebeling, Mara C; Bauer, Nichole A; Kopel, Lucas; Singh, Man Mohan; Halaweish, Fathi; Bell, Maria C; Jaggi, Meena; Chauhan, Subhash C

2015-01-28

101

Boswellic acid inhibits expression of acid sphingomyelinase in intestinal cells  

PubMed Central

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 boswellic acid, on acid SMase activity and expression in intestinal cells. Both transformed Caco-2 cells and non-transformed Int407 cells were incubated with AKBA. After incubation, the change of acid SMase activity was assayed biochemically, the enzyme protein was examined by Western blot, and acid SMase mRNA was quantified by qPCR. Results We found that AKBA decreased acid SMase activity in both intestinal cell lines in dose and time dependent manners without affecting the secretion of the enzyme to the cell culture medium. The effect of AKBA was more effective in the fetal bovine serum-free culture medium. Among different types of boswellic acid, AKBA was the most potent one. The inhibitory effect on acid SMase activity occurred only in the intact cells but not in cell-free extract in the test tubes. At low concentration, AKBA only decreased the acid SMase activity but not the quantity of the enzyme protein. However, at high concentration, AKBA decreased both the mass of acid SMase protein and the mRNA levels of acid SMase in the cells, as demonstrated by Western blot and qPCR, respectively. Under the concentrations decreasing acid SMase activity, AKBA significantly inhibited cell proliferation. Conclusion We identified a novel inhibitory effect of boswellic acids on acid SMase expression, which may have implications in human diseases and health. PMID:19951413

2009-01-01

102

Gambogic acid suppresses hypoxia-induced hypoxia-inducible factor-1?/vascular endothelial growth factor expression via inhibiting phosphatidylinositol 3-kinase/Akt/mammalian target protein of rapamycin pathway in multiple myeloma cells.  

PubMed

In multiple myeloma (MM), the hypoxic environment is an important factor causing tumor angiogenesis, which is strongly correlated to disease progression and unfavorable outcome by activating the key transcription factor, hypoxia-inducible factor-1? (HIF-1?). Gambogic acid (GA) is the major active ingredient of gamboge, which has been shown to possess antitumor effect by in vitro and in vivo study. However, the underlying molecular mechanism of whether GA inhibits tumor angiogenesis remains poorly understood. In this study, we investigated the effects of GA on expression of HIF-1?, and its downstream target gene vascular endothelial growth factor (VEGF) in human MM U266 cells. We found that hypoxia induced increase in the level of HIF-1? subunit protein and activated the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target protein of rapamycin (mTOR) pathway. Moreover, the treatment with GA markedly decreased HIF-1? and VEGF expression under hypoxic conditions. Mechanistic studies exhibited that GA inhibited the production of HIF-1? by reducing phosphorylation of Akt and mTOR in U266 cells. Furthermore, in vivo study revealed that intravenous injection of GA once every other day for 2 weeks could suppress tumor volumes by antiangiogenesis activity. Taken together, our results identify that GA suppresses hypoxia-activated pathways that are linked to MM progression, at least partly, by the inhibition of the PI3K/Akt/mTOR signaling pathway. Therefore, GA may be a new potent therapeutic agent against human MM cells. PMID:24890366

Wang, Fei; Zhang, Wei; Guo, Liting; Bao, Wen; Jin, Nan; Liu, Ran; Liu, Ping; Wang, Yonghui; Guo, Qinglong; Chen, Baoan

2014-08-01

103

SPLUNC1 is associated with nasopharyngeal carcinoma prognosis and plays an important role in all-trans-retinoic acid-induced growth inhibition and differentiation in nasopharyngeal cancer cells.  

PubMed

Human SPLUNC1 can suppress nasopharyngeal carcinoma (NPC) tumor formation; however, the correlation between SPLUNC1expression and NPC patient prognosis has not been reported. In the present study, we used a large-scale sample of 1015 tissue cores to detect SPLUNC1 expression and its association with patient prognosis. SPLUNC1 expression was reduced in NPC samples compared to nontumor nasopharyngeal epithelium tissues. Positive expression of SPLUNC1 in NPC predicted a better prognosis (disease-free survival, P = 0.034; overall survival, P = 0.048). Cox's proportional hazards model revealed that SPLUNC1 could be a significant prognostic factor affecting disease-free survival (P = 0.027). A cDNA micro-array analyzed by significant analysis of micro-array (SAM) and ingenuity pathway analysis (IPA) revealed that an indirect interaction existed between SPLUNC1 and retinoic acid (RA) in the cancer regulatory network. To further investigate the molecular mechanisms involved, we utilized several bioinformatics tools and identified 12 retinoid X receptors heterodimer binding sites in the promoter region of the SPLUNC1 gene. The transcriptional activity of the SPLUNC1 promoter was up-regulated significantly by all-trans-retinoic acid (ATRA). SPLUNC1 and retinoic acid receptor expression were induced significantly by ATRA, and removal of ATRA led to a progressive loss of SPLUNC1 and retinoic acid receptor expression. ATRA inhibited proliferation and induced the differentiation of NPC cells. Interestingly, over-expression of SPLUNC1 sensitized NPC cells to ATRA, whereas knockdown of SPLUNC1 in HNE1 cells increased cell viability. Under SPLUNC1 knockdown conditions, differentiation was reversed by ATRA treatment. We concluded that SPLUNC1 could potentially predict prognosis for NPC patients and play an important role in ATRA-induced growth inhibition and differentiation in NPC cells. PMID:25161098

Zhang, Wenling; Zeng, Zhaoyang; Wei, Fang; Chen, Pan; Schmitt, David C; Fan, Songqing; Guo, Xiaofang; Liang, Fang; Shi, Lei; Liu, Zixin; Zhang, Zuping; Xiang, Bo; Zhou, Ming; Huang, Donghai; Tang, Ke; Li, Xiaoling; Xiong, Wei; Tan, Ming; Li, Guiyuan; Li, Xiayu

2014-11-01

104

Selenium nanoparticles inhibit Staphylococcus aureus growth  

PubMed Central

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

Tran, Phong A; Webster, Thomas J

2011-01-01

105

Decreased growth-induced water potential: A primary cause of growth inhibition at low water potentials  

Microsoft Academic Search

Cell enlargement depends on a growth-induced difference in water potential to move water into the cells. Water deficits decrease this potential difference and inhibit growth. To investigate whether the decrease causes the growth inhibition, pressure was applied to the roots of soybean seedlings and the growth and potential difference were monitored in the stems. In water-limited plants, the inhibited stem

Hiroshi Nonami; Yajun Wu; J. S. Boyer

1997-01-01

106

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

NASA Technical Reports Server (NTRS)

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.

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

1991-01-01

107

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

PubMed Central

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

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

108

Synthesis and proteasome inhibition of lithocholic acid derivatives.  

PubMed

A new class of proteasome inhibitors was synthesized using lithocholic acid as a scaffold. Modification at the C-3 position of lithocholic acid with a series of acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic acid hemiester derivative (13) displayed the most potent proteasome inhibition with IC(50) = 1.9 ?M. Enzyme kinetic analysis indicates that these lithocholic acid derivatives are noncompetitive inhibitors of the proteasome. PMID:21388808

Dang, Zhao; Lin, Andrew; Ho, Phong; Soroka, Dominique; Lee, Kuo-Hsiung; Huang, Li; Chen, Chin-Ho

2011-04-01

109

Synthesis and proteasome inhibition of lithocholic acid derivatives  

PubMed Central

A new class of proteasome inhibitors was synthesized using lithocholic acid as a scaffold. Modification at the C-3 position of lithocholic acid with a series of acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic acid hemiester derivative (13) displayed the most potent proteasome inhibition with IC50 = 1.9 ?M. Enzyme kinetic analysis indicates that these lithocholic acid derivatives are non-competitive inhibitors of the proteasome. PMID:21388808

Dang, Zhao; Lin, Andrew; Ho, Phong; Soroka, Dominique; Lee, Kuo-Hsiung; Huang, Li; Chen, Chin-Ho

2011-01-01

110

5-Aminolevulinic acid-induced protoporphyrin IX with multi-dose ionizing irradiation enhances host antitumor response and strongly inhibits tumor growth in experimental glioma in vivo.  

PubMed

Ionizing irradiation is a well?established therapeutic modality for malignant gliomas. Due to its high cellular uptake, 5?aminolevulinic acid (ALA) is used for fluorescence?guided resection of malignant gliomas. We have previously shown that 5?ALA sensitizes glioma cells to irradiation in vitro. The aim of the present study was to assess whether 5?ALA acts as a radiosensitizer in experimental glioma in vivo. Rats were subcutaneously injected with 9L gliosarcoma cells and administered 5?ALA. The accumulation of 5?ALA?induced protoporphyrin IX was confirmed by high?performance liquid chromatography (HPLC) analysis. Subcutaneous (s.c.) tumors were subsequently irradiated with 2 Gy/day for five consecutive days. In the experimental glioma model, high?performance liquid chromatography analysis revealed a high level of accumulation of 5?ALA?induced protoporphyrin IX in s.c. tumors 3 h after 5?ALA administration. Multi?dose ionizing irradiation induced greater inhibition of tumor growth in rats that were administered 5?ALA than in the non?5?ALA?treated animals. Immunohistochemical analysis of the s.c. tumors revealed that numerous ionized calcium?binding adapter molecule 1 (Iba1)?positive macrophages gathered at the surface of and within the s.c. tumors following multi?dose ionizing irradiation in combination with 5?ALA administration. By contrast, the s.c. tumors in the control group scarcely showed aggregation of Iba1?positive macrophages. These results suggested that multi?dose ionizing irradiation with 5?ALA induced not only a direct cytotoxic effect but also enhanced the host antitumor immune response and thus caused high inhibition of tumor growth in experimental glioma. PMID:25420581

Yamamoto, Junkoh; Ogura, Shun-Ichiro; Shimajiri, Shohei; Nakano, Yoshiteru; Akiba, Daisuke; Kitagawa, Takehiro; Ueta, Kunihiro; Tanaka, Tohru; Nishizawa, Shigeru

2015-03-01

111

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

Microsoft Academic Search

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

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

2000-01-01

112

Inhibition of Aluminum Oxyhydroxide Precipitation with Citric Acid  

SciTech Connect

Citric acid has been shown to act as an agent for increasing the solubility of aluminum oxyhydroxides in aqueous solutions of high (>2.47 mol/mol) hydroxide-to-aluminum ratios. Conversely, citric acid also colloidally stabilizes particles in aqueous suspensions of aluminum-containing particles. Solutions of aluminum chloride, with and without citric acid added, were titrated with NaO(aq). The presence and size of particles were determined using quasi-elastic light scattering. In solutions that contained no citric acid, particles formed instantaneously when NaOH(aq) was added but these were observed to rapidly diminish in size, disappearing at OH/Al ratios below 2.5 mol/mol. When the OH/Al ratio was raised beyond 2.5 by addingmoreNaOH(aq), suspensions of colloidally stable particles formed. Large polycations containing 13 aluminum atoms were detected by 27Al solution NMR in citric-acid-free solutions with OH/Al ratios slightly lower than 2.5. In comparison, adding citric acid to solutions of aluminum chloride inhibited the formation of large aluminum-containing polycations. The absence of the polycations prevents or retards the subsequent formation of particles, indicating that the polycations, when present, act as seeds to the formation of new particles. Particles did not form in solutions with a citric acid/aluminum ratio of 0.8 until sufficient NaOH(aq) was added to raise the OH/Al ratio to 3.29. By comparison, lower amounts of citric acid did not prevent particles from forming but did retard the rate of growth.

Dabbs, Daniel M.; Ramachandran, Usha; Lu, Sang; Liu, Jun; Wang, Li Q.; Aksay, Ilhan A.

2005-12-06

113

Contact-dependent inhibition of growth in Escherichia coli.  

PubMed

Bacteria have developed mechanisms to communicate and compete with each other for limited environmental resources. We found that certain Escherichia coli, including uropathogenic strains, contained a bacterial growth-inhibition system that uses direct cell-to-cell contact. Inhibition was conditional, dependent upon the growth state of the inhibitory cell and the pili expression state of the target cell. Both a large cell-surface protein designated Contact-dependent inhibitor A (CdiA) and two-partner secretion family member CdiB were required for growth inhibition. The CdiAB system may function to regulate the growth of specific cells within a differentiated bacterial population. PMID:16109881

Aoki, Stephanie K; Pamma, Rupinderjit; Hernday, Aaron D; Bickham, Jessica E; Braaten, Bruce A; Low, David A

2005-08-19

114

2,3-Dihydroxybenzoic acid electrospun into poly(D,L-lactide) (PDLLA)/poly(ethylene oxide) (PEO) nanofibers inhibited the growth of Gram-positive and Gram-negative bacteria.  

PubMed

Widespread emergence of antibiotic-resistant pathogens in recent years has restricted the treatment options for various infectious diseases. Investigation of alternative antimicrobial agents and therapies is thus of utmost importance. Electrospinning of 50 mg/ml 2,3-dihydroxybenzoic acid (DHBA) into 24 % (w/v) poly(D,L-lactide) (PDLLA) and poly(ethylene oxide) (PEO) (1:1) produced nanofibers with an average diameter of 401 ± 122 nm. DHBA released from the nanofibers (315 ± 0.04 µg/ml within 2 h) inhibited the growth of Pseudomonas aeruginosa Xen 5, Klebsiella pneumoniae Xen 39, Escherichia coli Xen 14, Salmonella typhimurium Xen 26, and Staphylococcus aureus strains Xen 30, Xen 31, and Xen 36. The reason for the rapid diffusion of DHBA from PEO:PDLLA may be due to formation of hydrogen bonds between the hydroxyl groups of DHBA and the C=O groups of the PDLLA. DHBA formed a strong interaction with PDLLA and increased the thermal stability of the nanofiber mesh. The DHBA-containing nanofibers were non-hemolytic, suggesting that they may be incorporated in the development of a wound dressing. PMID:24934995

Ahire, Jayesh J; Neppalli, Ramesh; Heunis, Tiaan D J; van Reenen, Albert J; Dicks, Leon M T

2014-11-01

115

Accumulation of Polyhydroxyalkanoic Acid Containing Large Amounts of Unsaturated Monomers in Pseudomonas fluorescens BM07 Utilizing Saccharides and Its Inhibition by 2-Bromooctanoic Acid  

PubMed Central

A psychrotrophic bacterium, Pseudomonas fluorescens BM07, which is able to accumulate polyhydroxyalkanoic acid (PHA) containing large amounts of 3-hydroxy-cis-5-dodecenoate unit up to 35 mol% in the cell from unrelated substrates such as fructose, succinate, etc., was isolated from an activated sludge in a municipal wastewater treatment plant. When it was grown on heptanoic acid (C7) to hexadecanoic acid (C16) as the sole carbon source, the monomer compositional characteristics of the synthesized PHA were similar to those observed in other fluorescent pseudomonads belonging to rRNA homology group I. However, growth on stearic acid (C18) led to no PHA accumulation, but instead free stearic acid was stored in the cell. The existence of the linkage between fatty acid de novo synthesis and PHA synthesis was confirmed by using inhibitors such as acrylic acid and two other compounds, 2-bromooctanoic acid and 4-pentenoic acid, which are known to inhibit ?-oxidation enzymes in animal cells. Acrylic acid completely inhibited PHA synthesis at a concentration of 4 mM in 40 mM octanoate-grown cells, but no inhibition of PHA synthesis occurred in 70 mM fructose-grown cells in the presence of 1 to 5 mM acrylic acid. 2-Bromooctanoic acid and 4-pentenoic acid were found to much inhibit PHA synthesis much more strongly in fructose-grown cells than in octanoate-grown cells over concentrations ranging from 1 to 5 mM. However, 2-bromooctanoic acid and 4-pentenoic acid did not inhibit cell growth at all in the fructose media. Especially, with the cells grown on fructose, 2-bromooctanoic acid exhibited a steep rise in the percent PHA synthesis inhibition over a small range of concentrations below 100 ?M, a finding indicative of a very specific inhibition, whereas 4-pentenoic acid showed a broad, featureless concentration dependence, suggesting a rather nonspecific inhibition. The apparent inhibition constant Ki (the concentration for 50% inhibition of PHA synthesis) for 2-bromooctanoic acid was determined to be 60 ?M, assuming a single-site binding of the inhibitor at a specific inhibition site. Thus, it seems likely that a coenzyme A thioester derivative of 2-bromooctanoic acid specifically inhibits an enzyme linking the two pathways, fatty acid de novo synthesis and PHA synthesis. We suggest that 2-bromooctanoic acid can substitute for the far more expensive (2,000 times) and cell-growth-inhibiting PHA synthesis inhibitor, cerulenin. PMID:11679314

Lee, Ho-Joo; Choi, Mun Hwan; Kim, Tae-Un; Yoon, Sung Chul

2001-01-01

116

FTY720 inhibits tumor growth and angiogenesis.  

PubMed

De novo malignancies and recurrence of tumors are some of the biggest threats to allograft recipients subjected to chronic immunosuppression. FTY720, a synthetic myriocin analogue, is an immunosuppressant that induces apoptosis of activated lymphocytes and prevents infiltration of lymphocytes into allografts, thereby prolonging allograft survival in a dose-dependent manner. Additionally, FTY720 was shown to prevent tumor growth and metastasis. Therefore, we examined the effect of FTY720 on angiogenesis in a HUVEC spheroid model. To substantiate our in vitro findings the effect of FTY720 was also tested in C57/B16 mice subcutaneously injected with Lewis Lung Carcinoma (LLC1) cells. After establishment of a palpable tumor the animals were treated daily with either saline or 1, 5, or 10 mg/kg FTY720. Subsequently, the tumor size was measured, periodically. In our experiments FTY720 showed a strong antiangiogenic effect, overcoming the stimulating effect of VEGF (20 ng/mL) even at subnanomolar concentrations. In vivo, FTY720 showed a dose-dependent inhibition of subcutaneous tumors, and the tumor size of animals treated with 10 mg/kg FTY720 was less than half of the size of tumors in control animals. In conclusion, FTY-720 demonstrated a strong antiangiogenic effect in vitro and a substantial antitumor effect in vivo. Presumably, the stabilizing effect of surrounding pericytes limits the effect of FTY720 in our mouse model. Therefore, a combination of FTY720 with an mTOR inhibitor might be the most favorable immunosuppressive drug combination for allograft recipients at risk for tumor development. PMID:15808563

Schmid, G; Guba, M; Papyan, A; Ischenko, I; Brückel, M; Bruns, C J; Jauch, K-W; Graeb, C

2005-01-01

117

Combination of a potent 20-epi-vitamin D3 analogue (KH 1060) with 9-cis-retinoic acid irreversibly inhibits clonal growth, decreases bcl-2 expression, and induces apoptosis in HL-60 leukemic cells.  

PubMed

All-trans retinoic acid (RA) is the first highly effective differentiation-inducing agent for remission induction in patients with acute promyelocytic leukemia. However, remissions are short-lived because the treatment fails to induce complete differentiation and fails to eradicate the malignant clone. To eliminate rapidly the malignant clone, in analogy with aggressive chemotherapy, the combination of potent differentiation- and apoptosis-inducing drugs working through different receptors and signal pathways may be useful. The active form of vitamin D3 (1,25-dihydroxyvitamin D3; 1,25(OH)2D3) inhibits proliferation and induces differentiation of myeloid leukemic cells. The 9-cis-RA, unlike all-trans-RA which binds only retinoic acid receptors, is a high affinity ligand for both retinoic acid receptors and retinoid X receptors. The aim of this study was to evaluate the therapeutic potential of combining a vitamin D(3) analogue, 20-epi-22-oxa-24a,26a,27a-tri-homo-1alpha,25(OH) 2D, (KH 1060), which belongs to the family of potent 20-epi-1,25(OH),D3 analogues, with 9-cis-RA by assessing their effects on the proliferation, differentiation, and apoptosis of the human leukemia cell line HL-60 in vitro. Our data show that KH 1060 alone is a very potent inhibitor of clonal proliferation of HL-60, but this effect is reversible, and that 9-cis-RA alone is a weak inhibitor of clonal proliferation of HL-60 cells. In contrast, the combination of KH 1060 and 9-cis-RA synergistically and irreversibly inhibited the clonal proliferation of HL-60 cells and induced apoptosis, as detected by morphological changes and DNA fragmentation. This combination also affected the expression of apoptosis-related genes. The bcl-2 protein became nearly undetectable, and expression of bax protein increased slightly (the bax:bcl-2 ratio was 14-fold higher than in untreated cells). Differentiation of treated HL-60 cells was assessed by their ability to produce superoxide, as measured by reduction of nitro blue tetrazolium, positive staining for alpha-naphthyl acetate esterase, phagocytosis, morphology, and analysis of membrane-bound differentiation markers with two-color immunofluorescence. Treatment with the combination of KH 1060 and 9-cis-RA was a potent inducer of differentiation of HL-60, with the cells developing a myelomonocytic phenotype. In summary, our data demonstrate that the combination of both KH 1060 and 9-cis-RA irreversibly and synergistically inhibited clonal growth, induced differentiation and apoptosis of HL-60 cells concomitantly with a very marked decreased expression of bcl-2, and increased the bax:bcl-2 ratio. This drug combination may have important therapeutic significance. PMID:8758928

Elstner, E; Linker-Israeli, M; Umiel, T; Le, J; Grillier, I; Said, J; Shintaku, I P; Krajewski, S; Reed, J C; Binderup, L; Koeffler, H P

1996-08-01

118

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

PubMed Central

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

2013-01-01

119

Novel Approaches to Inhibition of Gastric Acid Secretion  

PubMed Central

The gastric H,K-adenosine triphosphatase (ATPase) is the primary target for treatment of acid-related diseases. Proton pump inhibitors (PPIs) are weak bases composed of two moieties, a substituted pyridine with a primary pKa of about 4.0 that allows selective accumulation in the secretory canaliculus of the parietal cell, and a benzimidazole with a second pKa of about 1.0. Protonation of this benzimidazole activates these prodrugs, converting them to sulfenic acids and/or sulfenamides that react covalently with one or more cysteines accessible from the luminal surface of the ATPase. The maximal pharmacodynamic effect of PPIs as a group relies on cyclic adenosine monophosphate–driven H,K-ATPase translocation from the cytoplasm to the canalicular membrane of the parietal cell. At present, this effect can only be achieved with protein meal stimulation. Because of covalent binding, inhibitory effects last much longer than their plasma half-life. However, the short dwell-time of the drug in the blood and the requirement for acid activation impair their efficacy in acid suppression, particularly at night. All PPIs give excellent healing of peptic ulcer and produce good, but less than satisfactory, results in reflux esophagitis. PPIs combined with antibiotics eradicate Helicobacter pylori, but success has fallen to less than 80%. Longer dwell-time PPIs promise to improve acid suppression and hence clinical outcome. Potassium-competitive acid blockers (P-CABs) are another class of ATPase inhibitors, and at least one is in development. The P-CAB under development has a long duration of action even though its binding is not covalent. PPIs with a longer dwell time or P-CABs with long duration promise to address unmet clinical needs arising from an inability to inhibit nighttime acid secretion, with continued symptoms, delayed healing, and growth suppression of H. pylori reducing susceptibility to clarithromycin and amoxicillin. Thus, novel and more effective suppression of acid secretion would benefit those who suffer from acid-related morbidity, continuing esophageal damage and pain, nonsteroidal anti-inflammatory drug–induced ulcers, and nonresponders to H. pylori eradication. PMID:20924727

Shin, Jai Moo; Hunt, Richard

2010-01-01

120

Novel approaches to inhibition of gastric acid secretion.  

PubMed

The gastric H,K-adenosine triphosphatase (ATPase) is the primary target for treatment of acid-related diseases. Proton pump inhibitors (PPIs) are weak bases composed of two moieties, a substituted pyridine with a primary pK(a) of about 4.0 that allows selective accumulation in the secretory canaliculus of the parietal cell, and a benzimidazole with a second pK(a) of about 1.0. Protonation of this benzimidazole activates these prodrugs, converting them to sulfenic acids and/or sulfenamides that react covalently with one or more cysteines accessible from the luminal surface of the ATPase. The maximal pharmacodynamic effect of PPIs as a group relies on cyclic adenosine monophosphate-driven H,K-ATPase translocation from the cytoplasm to the canalicular membrane of the parietal cell. At present, this effect can only be achieved with protein meal stimulation. Because of covalent binding, inhibitory effects last much longer than their plasma half-life. However, the short dwell-time of the drug in the blood and the requirement for acid activation impair their efficacy in acid suppression, particularly at night. All PPIs give excellent healing of peptic ulcer and produce good, but less than satisfactory, results in reflux esophagitis. PPIs combined with antibiotics eradicate Helicobacter pylori, but success has fallen to less than 80%. Longer dwell-time PPIs promise to improve acid suppression and hence clinical outcome. Potassium-competitive acid blockers (P-CABs) are another class of ATPase inhibitors, and at least one is in development. The P-CAB under development has a long duration of action even though its binding is not covalent. PPIs with a longer dwell time or P-CABs with long duration promise to address unmet clinical needs arising from an inability to inhibit nighttime acid secretion, with continued symptoms, delayed healing, and growth suppression of H. pylori reducing susceptibility to clarithromycin and amoxicillin. Thus, novel and more effective suppression of acid secretion would benefit those who suffer from acid-related morbidity, continuing esophageal damage and pain, nonsteroidal anti-inflammatory drug-induced ulcers, and nonresponders to H. pylori eradication. PMID:20924727

Sachs, George; Shin, Jai Moo; Hunt, Richard

2010-12-01

121

Growth inhibition of human gastrointestinal cancer cells by cyclosporin A.  

PubMed

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

Piontek, M; Porschen, R

1994-01-01

122

Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro  

Microsoft Academic Search

We report here that glycyrrhizic acid (GL), a component of licorice root (Glycyrrhiza radix), is active against EBV replication in superinfected Raji cells in a dose-dependent fashion. The IC50 values for viral inhibition and cell growth were 0.04 and 4.8mM, respectively. The selectivity index (ratio of IC50 for cell growth to IC50 for viral DNA synthesis) was 120. Time of

Jung-Chung Lin

2003-01-01

123

Calcium ion involvement in growth inhibition of mechanically stressed soybean (Glycine max) seedlings  

NASA Technical Reports Server (NTRS)

A 40-50% reduction in soybean [Glycine max (L.) Merr. cv. Century 84] hypocotyl elongation occurred 24 h after application of mechanical stress. Exogenous Ca2+ at 10 mM inhibited growth by 28% if applied with the Ca2+ ionophore A23187 to the zone of maximum hypocotyl elongation. La3+ was even more inhibitory than Ca2+, especially above 5 mM. Treatment with ethyleneglycol-bis-(beta-aminoethylether)-N, N, N', N'-tetraacetic acid (EGTA) alone had no effect on growth of non-stressed seedlings at the concentrations used but negated stress-induced growth reduction by 36% at 4 mM when compared to non-treated, stressed controls. Treatment with EDTA was ineffective in negating stress-induced growth inhibition. Calmodulin antagonists calmidazolium, chlorpromazine, and 48/80 also negated stress-induced growth reduction by 23, 50, and 35%, respectively.

Jones, R. S.; Mitchell, C. A.

1989-01-01

124

Timing of growth inhibition following shoot inversion in Pharbitis nil  

NASA Technical Reports Server (NTRS)

Shoot inversion in Pharbitis nil results in the enhancement of ethylene production and in the inhibition of elongation in the growth zone of the inverted shoot. The initial increase in ethylene production previously was detected within 2 to 2.75 hours after inversion. In the present study, the initial inhibition of shoot elongation was detected within 1.5 to 4 hours with a weighted mean of 2.4 hours. Ethylene treatment of upright shoots inhibited elongation in 1.5 hours. A cause and effect relationship between shoot inversion-enhanced ethylene production and inhibition of elongation cannot be excluded.

Abdel-Rahman, A. M.; Cline, M. G.

1989-01-01

125

Root growth inhibition by NH4 in Arabidopsis is mediated  

E-print Network

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

Kronzucker, Herbert J.

126

Inhibition of rate of tumor growth by creatine and cyclocreatine.  

PubMed

Growth rate inhibition of subcutaneously implanted tumors results from feeding rats and athymic nude mice diets containing 1% cyclocreatine or 1%, 2%, 5%, or 10% creatine. The tumors studied included rat mammary tumors (Ac33tc in Lewis female rats and 13762A in Fischer 344 female rats), rat sarcoma MCI in Lewis male rats, and tumors resulting from the injection of two human neuroblastoma cell lines, IMR-5 and CHP-134, in athymic nude mice. Inhibition was observed regardless of the time experimental diets were administered, either at the time of tumor implantation or after the appearance of palpable tumors. For mammary tumor Ac33tc, the growth inhibition during 24 days after the implantation was approximately 50% for both 1% cyclocreatine and 1% creatine, and inhibition increased as creatine was increased from 2% to 10% of the diet. For the other rat mammary tumor (13762A), there was approximately 35% inhibition by both 1% cyclocreatine and 2% creatine. In the case of the MCI sarcoma, the inhibitory effect appeared more pronounced at earlier periods of growth, ranging from 26% to 41% for 1% cyclocreatine and from 30% to 53% for 1% creatine; there was no significant difference in growth rate between the tumors in the rats fed 1% and 5% creatine. The growth rate of tumors in athymic nude mice, produced by implantation of the human neuroblastoma IMR-5 cell line, appeared somewhat more effectively inhibited by 1% cyclocreatine than by 1% creatine, and 5% creatine feeding was most effective. For the CHP-134 cell line, 33% inhibition was observed for the 1% cyclocreatine diet and 71% for the 5% creatine diet. In several experiments, a delay in appearance of tumors was observed in animals on the experimental diets. In occasional experiments, neither additive inhibited tumor growth rate for the rat tumors or the athymic mouse tumors. PMID:8475072

Miller, E E; Evans, A E; Cohn, M

1993-04-15

127

Inhibition of stem growth and gibberellin production in Agrostemma githago L. by the growth retardant tetcyclacis.  

PubMed

The effects of the new growth retardant tetcyclacis (TCY) on stem growth and endogenous gibberellin (GA) levels were investigated in the long-day rosette plant Agrostemma githago. Application of TCY (10 ml of a 5·10(-5)M solution daily) to the soil suppressed stem elongation in Agrostemma grown under long-day conditions. A total of 10 ?g GA1 (1 ?g applied on alternate days) per plant overcame the growth retardation caused by TCY.Control plants and plants treated with TCY were analyzed for endogenous GAs after exposure to nine long days. The acidic extracts were fractionated by high-performance liquid chromatography. Part of each fraction was tested in the d-5 maize bioassay, while the remainder was analyzed by combined gas chromatography-selected ion monitoring. The bioassay results indicated that the GA content of plants treated with TCY was much lower than that of untreated plants. The data obtained by gas chromatography-selected ion monitoring confirmed that the levels of seven GAs present in Agrostemma were much reduced in TCY-treated plants when compared with the levels in control plants: GA53 (13%), GA44 (0%), GA19 (1%), GA17 (33%), GA20 (15%), GA1 (4%), and epi-GA1 (13%). These results provide evidence that TCY inhibits stem growth in Agrostemma by blocking GA biosynthesis and thus lowering the levels of endogenous GAs. PMID:24241444

Zeevaart, J A

1985-10-01

128

Transcriptional profile of maize roots under acid soil growth  

PubMed Central

Background Aluminum (Al) toxicity is one of the most important yield-limiting factors of many crops worldwide. The primary symptom of Al toxicity syndrome is the inhibition of root growth leading to poor water and nutrient absorption. Al tolerance has been extensively studied using hydroponic experiments. However, unlike soil conditions, this method does not address all of the components that are necessary for proper root growth and development. In the present study, we grew two maize genotypes with contrasting tolerance to Al in soil containing toxic levels of Al and then compared their transcriptomic responses. Results When grown in acid soil containing toxic levels of Al, the Al-sensitive genotype (S1587-17) showed greater root growth inhibition, more Al accumulation and more callose deposition in root tips than did the tolerant genotype (Cat100-6). Transcriptome profiling showed a higher number of genes differentially expressed in S1587-17 grown in acid soil, probably due to secondary effects of Al toxicity. Genes involved in the biosynthesis of organic acids, which are frequently associated with an Al tolerance response, were not differentially regulated in both genotypes after acid soil exposure. However, genes related to the biosynthesis of auxin, ethylene and lignin were up-regulated in the Al-sensitive genotype, indicating that these pathways might be associated with root growth inhibition. By comparing the two maize lines, we were able to discover genes up-regulated only in the Al-tolerant line that also presented higher absolute levels than those observed in the Al-sensitive line. These genes encoded a lipase hydrolase, a retinol dehydrogenase, a glycine-rich protein, a member of the WRKY transcriptional family and two unknown proteins. Conclusions This work provides the first characterization of the physiological and transcriptional responses of maize roots when grown in acid soil containing toxic levels of Al. The transcriptome profiles highlighted several pathways that are related to Al toxicity and tolerance during growth in acid soil. We found several genes that were not found in previous studies using hydroponic experiments, increasing our understanding of plant responses to acid soil. The use of two germplasms with markedly different Al tolerances allowed the identification of genes that are a valuable tool for assessing the mechanisms of Al tolerance in maize in acid soil. PMID:20828383

2010-01-01

129

Inhibition of Aluminum Oxyhydroxide Precipitation with Citric Acid  

E-print Network

Inhibition of Aluminum Oxyhydroxide Precipitation with Citric Acid Daniel M. Dabbs, Usha as an agent for increasing the solubility of aluminum oxyhydroxides in aqueous solutions of high (>2.47 mol/mol) hydroxide-to-aluminum ratios. Conversely, citric acid also colloidally stabilizes particles in aqueous

Aksay, Ilhan A.

130

Acid inhibition of CRA`s: A review  

SciTech Connect

This paper will review the brief history in the literature of the inhibition of corrosion resistant alloys (CRA`s) in acidic stimulation fluids. This review primarily discusses the problems associated with inhibiting 13% Cr and 22% Cr duplex steels in hydrochloric (HCI) and hydrochloric-hydrofluoric (HCl-HF) acid systems using low alloy inhibitors and the successes achieved using high alloy inhibitors. Other areas briefly discussed are the repassivation of 13% Cr and 22% Cr, effect on nickel-based alloys and use of organic acids.

Walker, M.L.; Cassidy, J.M.; Lancaster, K.R.; McCoy, T.H. [Halliburton Energy Services, Duncan, OK (United States)

1994-12-31

131

Sugar fatty acid esters inhibit biofilm formation by food-borne pathogenic bacteria  

PubMed Central

Effects of food additives on biofilm formation by food-borne pathogenic bacteria were investigated. Thirty-three potential food additives and 3 related compounds were added to the culture medium at concentrations from 0.001 to 0.1% (w/w), followed by inoculation and cultivation of five biofilm-forming bacterial strains for the evaluation of biofilm formation. Among the tested food additives, 21 showed inhibitory effects of biofilm formation by Staphylococcus aureus and Escherichia coli, and in particular, sugar fatty acid esters showed significant anti-biofilm activity. Sugar fatty acid esters with long chain fatty acid residues (C14-16) exerted their inhibitory effect at the concentration of 0.001%(w/w), but bacterial growth was not affected at this low concentration. Activities of the sugar fatty acid esters positively correlated with the increase of the chain length of the fatty acid residues. Sugar fatty acid esters inhibited the initial attachment of the Staphylococcus aureus cells to the abiotic surface. Sugar fatty acid esters with long chain fatty acid residues (C14-16) also inhibited biofilm formation by Streptococcus mutans and Listeria monocytogenes at 0.01%(w/w), while the inhibition of biofilm formation by Pseudomonas aeruginosa required the addition of a far higher concentration (0.1%(w/w)) of the sugar fatty acid esters. PMID:20089325

Furukawa, Soichi; Akiyoshi, Yuko; O’Toole, George A.; Ogihara, Hirokazu; Morinaga, Yasushi

2010-01-01

132

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

PubMed

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

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

2015-02-01

133

Oligodendrocytes Arrest Neurite Growth by Contact Inhibition  

Microsoft Academic Search

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

Christine Bandtlow; Thomas Zachleder; Martin E. Schwab

1990-01-01

134

Inhibition of prostatic cancer growth by ginsenoside Rh2.  

PubMed

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

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

2014-11-23

135

Human müllerian inhibiting substance inhibits tumor growth in vitro and in vivo.  

PubMed

Müllerian inhibiting substance (MIS) causes regression of the müllerian duct in the male fetus. Bovine MIS has been reported to inhibit the growth of some gynecological tumors. Recombinant human MIS (rhMIS) produced in transfected Chinese hamster ovary cells has been highly purified by immunoaffinity chromatography. The introduction of a salt wash prior to elution of MIS from the affinity column removes a growth-stimulating factor(s) derived from Chinese hamster ovary cells. This immunopurified rhMIS caused significant inhibition (34-59% survival) of A431 (a vulvar epidermoid carcinoma), HT-3 (a cervical carcinoma), HEC-1-A (an endometrial adenocarcinoma), NIH:OVCAR-3 (an ovarian adenocarcinoma), and OM431 (an ocular melanoma) human cell lines in colony inhibition assays. Two cell lines, Hep 3B (a hepatocellular carcinoma) and RT4 (a bladder transitional cell papilloma), were unresponsive to immunopurified rhMIS. Using an in vivo subrenal capsule assay in irradiated CD-1 mice, the growth of A431 and OM431 cells was inhibited by immunopurified rhMIS. We conclude that rhMIS inhibits the growth of certain tumor cell lines in vitro and in vivo. PMID:2009529

Chin, T W; Parry, R L; Donahoe, P K

1991-04-15

136

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

SciTech Connect

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.

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

137

Conjugated Linoleic Acid Inhibits Proliferation and Induces Apoptosis of Normal Rat Mammary Epithelial Cells in Primary Culture  

Microsoft Academic Search

The trace fatty acid conjugated linoleic acid (CLA) inhibits rat mammary carcinogenesis when fed prior to carcinogen during pubertal mammary gland development or during the promotion phase of carcinogenesis. The following studies were done to investigate possible mechanisms of these effects. Using a physiological model for growth and differentiation of normal rat mammary epithelial cell organoids (MEO) in primary culture,

Margot M. Ip; Patricia A. Masso-Welch; Suzanne F. Shoemaker; Wendy K. Shea-Eaton; Clement Ip

1999-01-01

138

Effect of pH alkaline salts of fatty acids on the inhibition of bacteria associated with poultry processing  

Technology Transfer Automated Retrieval System (TEKTRAN)

The agar diffusion assay was used to examine the effect of pH on the ability of alkaline salts of three fatty acids (FA) to inhibit growth of bacteria associated with poultry processing. FA solutions were prepared by dissolving 0.5 M concentrations of caprylic, capric, or lauric acid in separate ali...

139

Growth of nitric acid hydrates on thin sulfuric acid films  

NASA Technical Reports Server (NTRS)

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.

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

1994-01-01

140

Boswellic acid inhibits expression of acid sphingomyelinase in intestinal cells  

Microsoft Academic Search

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

Yao Zhang; Rui-Dong Duan

2009-01-01

141

Inhibition of tumor-stromal interaction through HGF/Met signaling by valproic acid  

SciTech Connect

Hepatocyte growth factor (HGF), which is produced by surrounding stromal cells, including fibroblasts and endothelial cells, has been shown to be a significant factor responsible for cancer cell invasion mediated by tumor-stromal interactions. We found in this study that the anti-tumor agent valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, strongly inhibited tumor-stromal interaction. VPA inhibited HGF production in fibroblasts induced by epidermal growth factor (EGF), platelet-derived growth factor, basic fibroblast growth factor, phorbol 12-myristate 13-acetate (PMA) and prostaglandin E{sub 2} without any appreciable cytotoxic effect. Other HDAC inhibitors, including butyric acid and trichostatin A (TSA), showed similar inhibitory effects on HGF production stimulated by various inducers. Up-regulations of HGF gene expression induced by PMA and EGF were also suppressed by VPA and TSA. Furthermore, VPA significantly inhibited HGF-induced invasion of HepG2 hepatocellular carcinoma cells. VPA, however, did not affect the increases in phosphorylation of MAPK and Akt in HGF-treated HepG2 cells. These results demonstrated that VPA inhibited two critical processes of tumor-stromal interaction, induction of fibroblastic HGF production and HGF-induced invasion of HepG2 cells, and suggest that those activities serve for other anti-tumor mechanisms of VPA besides causing proliferation arrest, differentiation, and/or apoptosis of tumor cells.

Matsumoto, Yohsuke; Motoki, Takahiro [Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-naka, Okayama 700-8530 (Japan); Kubota, Satoshi; Takigawa, Masaharu [Department of Biochemistry and Molecular Dentistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Okayama 700-8525 (Japan); Tsubouchi, Hirohito [Digestive Disease and Life-style Related Disease, Health Research Human and Environmental Sciences, Kagoshima University, Graduate School of Medicine and Dental Sciences, Sakuragaoka, Kagoshima 890-8520 (Japan); Gohda, Eiichi [Department of Immunochemistry, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-naka, Okayama 700-8530 (Japan)], E-mail: gohda@pheasant.pharm.okayama-u.ac.jp

2008-02-01

142

Inhibition of Listeria innocua in hummus by a combination of nisin and citric acid.  

PubMed

The effect of nisin or citric acid or combinations of these two inhibitors on the inactivation of a cocktail of three Listeria innocua strains was investigated in a model brain heart infusion (BHI) broth and hummus (chickpea dip). In BHI broth, citric acid had a limited ability to inhibit L. innocua growth. Nisin initially reduced L. innocua concentrations by about 3 log cycles; however, L. innocua reached concentrations similar to those of the control after 5 days at 22 degrees C. In combination, the effects of 500 IU/ml nisin and 0.2% citric acid were synergistic and resulted in complete elimination of L. innocua in the BHI broth. The inhibition of L. innocua by nisin (500 or 1,000 IU/g), citric acid (0.1, 0.2, or 0.3%), or their combinations also was evaluated in hummus. Citric acid alone did not affect L. innocua growth or the aerobic bacterial plate count. A combination of 1,000 IU/g nisin and 0.3% citric acid was somewhat effective (approximately 1.5-log reduction) in controlling the concentration of L. innocua and the aerobic plate count for up to 6 days. This combination also may be useful, in addition to proper hygienic practices, for minimizing the growth of the pathogen Listeria monocytogenes in hummus. PMID:16786852

Al-Holy, M; Al-Qadiri, H; Lin, M; Rasco, B

2006-06-01

143

Multiple product inhibition and growth modeling of Clostridium butyricum and Klebsiella pneumoniae in glycerol fermentation  

SciTech Connect

The inhibition potentials of products and substrate on the growth of Clostridium butyricum and Klebsiella pneumoniae in the glycerol fermentation are examined from experimental data and with a mathematical model. Whereas the inhibition potential of externally added and self-produced 1,3-propanediol is essentially the same, butyric acid produced by the culture is more toxic than that externally added. The same seems to apply for acetic acid. The inhibitory effect of butyric acid is due to the total concentration instead of its undissociated form. For acetic acid, it cannot be distinguished between the total concentration and the undissociated form. The inhibition effects of products and substrate in the glycerol fermentation are irrespective of the strains, and, therefore, the same growth model can be used. The maximum product concentrations tolerated are 0.35 g/L for undissociated acetic acid, 10.1 g/L for total butyric acid, 16.6 g/L for ethanol, 71.4 g/L for 1,3-propanediol, and 187.6 g/L for glycerol, which are applicable to C. butyricum and K. pneumoniae growth under a variety of conditions. For 55 steady-states, which were obtained from different types of continuous cultures over a pH range of 5.3--8.5 and under both substrate limitation and substrate excess, the proposed growth model fits the experimental data with an average deviation of 17.0%. The deviation of model description from experimental values reduces of 11.4% if only the steady-states with excessive substrate are considered.

Zeng, A.P.; Ross, A.; Biebl, H.; Tag, C.; Guenzel, B.; Deckwer, W.D. (Gesellschaft fuer Biotechnologische Forschung mbH, Braunschweig (Germany). Biochemical Engineering Division)

1994-10-01

144

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

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.

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

145

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

PubMed

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 G0/G1 cell cycle arrest and increased levels of the CDK inhibitor p27(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 G0/G1 cell cycle phase arrest and increased levels of p27(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 G0 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. PMID:24269815

Suzuki, Kanayo; Sakaguchi, Minoru; Tanaka, Satoshi; Yoshimoto, Tadashi; Takaoka, Masanori

2014-01-01

146

A somatostatin analogue inhibits chondrosarcoma and insulinoma tumour growth.  

PubMed

The in vivo effects on tumour growth of a potent somatostatin analogue, SMS 201-995 [H-(D)Phe-Cys-Phe-(D)Trp-Lys-Thr-Cys-Thr-(ol)], were measured in two characterised transplantable tumours: a) the Swarm rat chondrosarcoma, known to be insulin-, growth hormone (GH)-, somatomedin- and corticosteroid-dependent, b) a hamster insulinoma, bearing specific high affinity somatostatin receptors. SMS 201-995 (1.25 mg/kg/day) given for 25 days to rats bearing freshly transplanted chondrosarcomas inhibited tumour volume by 48%. A significant tumour growth inhibition was measured also in well developed tumours treated with high doses of SMS 201-995 (1.25mg/kg/day) for 7 days. In the treated animals, GH was significantly inhibited. In hamsters bearing a freshly transplanted insulinoma, the daily application of SMS 201-995 (200 micrograms/kg/day, sc) for 33 days could significantly inhibit the growth (as measured by tumour volume) of the tumour. A moderate inhibitory effect of SMS 201-995 on the growth of well grown insulinomas could also be observed. This study shows that SMS 201-995 under the present experimental conditions has a moderate but significant growth inhibitory effect in two different transplantable tumour models. In the rat chondrosarcoma, the effect of SMS 201-995 is probably indirect, due to inhibition of GH, somatomedin and insulin. In the hamster insulinoma, the effect is possibly due to a more direct action of SMS 201-995 on specific somatostatin receptors present in this tumour. PMID:2860768

Reubi, J C

1985-05-01

147

Algal growth inhibition effects and inducement modes by plant-producing phenols.  

PubMed

Evaluated here are the inhibitory effects on blue-green algae (Microcystis aeruginosa) produced by nine plant-producing phenols (caffeic, p-coumaric, ferulic, protocatechuic, sinapic, syringic, and vanillic acids, catechol, and hydroquinone), two plant-produced acids (quinic and shikimic acid), phenol, resorcinol, hydroxy hydroquinone, and phloroglucinol. Algal assays confirmed growth inhibition of M. aeruginosa by polyphenols, i.e., caffeic/protocatechuic acid, catechol, hydroquinone, hydroxy hydroquinone, and phloroglucinol, and by phenols containing methoxy groups, i.e., vanillic, sinapic, and syringic acids. Accordingly, this indicates good feasibility for controlling growth of M. aeruginosa using such plant-producing polyphenols and/or phenols as additives. A comparison of the inhibitory effects of the polyphenols showed that those induced by polyphenols in which phenolic hydroxy groups bound a benzene ring at ortho- and/or para-positions to another phenolic hydroxy group are stronger than the effects induced by polyphenols in which phenolic hydroxy groups are at only meta-positions. Experiments showed that the only polyphenols demonstrating significant growth inhibition of M. aeruginosa were autoxidized. These results suggest that autoxidation of the polyphenols induces inhibitory effects by producing polyphenol-autoxidized products such as radicals. PMID:11329689

Nakai, S; Inoue, Y; Hosomi, M

2001-05-01

148

Rosiglitazone Regulates Anti-Inflammation and Growth Inhibition via PTEN  

PubMed Central

Peroxisome proliferator-activated receptor gamma (PPAR?) agonist has anti-inflammatory and anticancer properties. However, the mechanisms by which PPAR? agonist rosiglitazone interferes with inflammation and cancer via phosphatase and tensin homolog-(PTEN)-dependent pathway remain unclear. We found that lower doses (<25??M) of rosiglitazone significantly inhibited lipopolysaccharide-(LPS)-induced nitric oxide (NO) release (via inducible nitric oxide synthase, iNOS), prostaglandin E2 (PGE2) production (via cyclooxygenase-2, COX-2), and activation of Akt in RAW 264.7 murine macrophages. However, rosiglitazone did not inhibit the production of reactive oxygen species (ROS). In PTEN knockdown (shPTEN) cells exposed to LPS, rosiglitazone did not inhibit NO release, PGE2 production, and activation of Akt. These cells had elevated basal levels of iNOS, COX-2, and ROS. However, higher doses (25–100??M) of rosiglitazone, without LPS stimulation, did not block NO release and PGE2 productions, but they inhibited p38 MAPK phosphorylation and blocked ROS generation in shPTEN cells. In addition, rosiglitazone caused G1 arrest and reduced the number of cells in S?+?G2/M phase, leading to growth inhibition. These results indicate that the anti-inflammatory property of rosiglitazone is related to regulation of PTEN independent of inhibition on ROS production. However, rosiglitazone affected the dependence of PTEN-deficient cell growth on ROS. PMID:24757676

Lin, Chiou-Feng; Young, Kung-Chia; Bai, Chyi-Huey; Yu, Bu-Chin; Ma, Ching-Ting; Chien, Yu-Chieh; Chiang, Chiu-Ling; Liao, Chao-Sheng; Lai, Hsin-Wen; Tsao, Chiung-Wen

2014-01-01

149

Growth Inhibition of Sympathetic Cells by Some Adrenergic Blocking Agents  

PubMed Central

Treatment of newborn mice and rats with the adrenergic blocking agents, guanethidine and bretylium tosylate, results in massive destruction of immature sympathetic nerve cells. A growth inhibition of the same cells is caused by reserpine. Similarities and differences between the effects elicited by these three ganglion blocking agents and a dopamine analog, 6-hydroxydopamine, are discussed. Images PMID:4333047

Angeletti, Pietro U.; Levi-Montalcini, Rita

1972-01-01

150

Chlorinated Englerins with Selective Inhibition of Renal Cancer Cell Growth#  

PubMed Central

A series of chlorinated englerins (3–9), were isolated from Phyllanthus engleri and shown to selectively inhibit the growth of renal cancer cells. The compounds were shown to be extraction artifacts produced by exposure to chloroform decomposition products during their isolation. The most active compound, 3, was synthesized from englerin A (1). PMID:22280462

Akee, Rhone K.; Ransom, Tanya; Ratnayake, Ranjala; McMahon, James B.; Beutler, John A.

2012-01-01

151

Phytotoxicity of nanoparticles: Inhibition of seed germination and root growth  

Microsoft Academic Search

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

Daohui Lin; Baoshan Xing

2007-01-01

152

Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas  

Microsoft Academic Search

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

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

153

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

PubMed Central

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

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

2013-01-01

154

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

PubMed Central

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

2013-01-01

155

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

PubMed Central

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

2014-01-01

156

Effects of acidity on tree pollen germination and tube growth  

SciTech Connect

Several studies have indicated that pollen germination and tube growth are adversely affected by air pollutants. Pollutants may inhibit the function of pollen by reducing the number of pollen grains which germinate, by reducing the maximum length to which the pollen tubes grow, or by interfering with the formation of the generative cell. The paper reports on studies that are attempting to determine the effects acid rain may have on these crucial stages in the life histories of northeastern tree species. The first stage of this work assessed the effects of acidity in the growth medium on in vitro pollen germination for four deciduous forest species common to central New York State, Betula lutea (yellow birch), B. lenta (black birch), Acer saccharum (sugar maple), and Cornus florida (flowering dogwood). Measurements were taken at the end of the growth period to determine the percentage of grains which had germinated, and to estimate the average tube length. To determine the effects of pollen on the growth medium, the pH of the germination drop was measured at the end of the growth period.

Jacobson, J.S.; Van Rye, D.M.; Lassoie, J.P.

1985-01-01

157

Phosphatidic acid inhibits ceramide 1-phosphate-stimulated macrophage migration.  

PubMed

Ceramide 1-phosphate (C1P) was recently demonstrated to potently induce cell migration. This action could only be observed when C1P was applied exogenously to cells in culture, and was inhibited by pertussis toxin. However, the mechanisms involved in this process are poorly understood. In this work, we found that phosphatidic acid (PA), which is structurally related to C1P, displaced radiolabeled C1P from its membrane-binding site and inhibited C1P-stimulated macrophage migration. This effect was independent of the saturated fatty acid chain length or the presence of a double bond in each of the fatty acyl chains of PA. Treatment of RAW264.7 macrophages with exogenous phospholipase D (PLD), an enzyme that produces PA from membrane phospholipids, also inhibited C1P-stimulated cell migration. Likewise, PA or exogenous PLD inhibited C1P-stimulated extracellularly regulated kinases (ERK) 1 and 2 phosphorylation, leading to inhibition of cell migration. However, PA did not inhibit C1P-stimulated Akt phosphorylation. It is concluded that PA is a physiological regulator of C1P-stimulated macrophage migration. These actions of PA may have important implications in the control of pathophysiological functions that are regulated by C1P, including inflammation and various cellular processes associated with cell migration such as organogenesis or tumor metastasis. PMID:25450673

Ouro, Alberto; Arana, Lide; Rivera, Io-Guané; Ordoñez, Marta; Gomez-Larrauri, Ana; Presa, Natalia; Simón, Jorge; Trueba, Miguel; Gangoiti, Patricia; Bittman, Robert; Gomez-Muñoz, Antonio

2014-10-18

158

Corrosion inhibition in concrete arising from its acid neutralisation capacity  

Microsoft Academic Search

It has been postulated that the most important inhibitive property of concrete affecting the level of chloride required to initiate corrosion is its ability to resist a local fall in pH that might otherwise sustain passive film breakdown at a developing pit. In this work a novel technique termed differential acid neutralisation analysis was used to characterise this property. It

G. K. Glass; B. Reddy; N. R. Buenfeld

2000-01-01

159

Fatty Acid Amide Hydrolase Inhibition by Neurotoxic Organophosphorus Pesticides  

Microsoft Academic Search

Organophosphorus (OP) compound-induced inhibition of acetylcholinesterase (AChE) and neuropathy target esterase explains the rapid onset and delayed neurotoxic effects, respectively, for OP insecticides and related compounds but apparently not a third or intermediate syndrome with delayed onset and reduced limb mobility. This investigation tests the hypothesis that fatty acid amide hydrolase (FAAH), a modulator of endogenous signaling compounds affecting sleep

Gary B. Quistad; Susan E. Sparks; John E. Casida

2001-01-01

160

Inhibition of tumor growth by elimination of granulocytes  

PubMed Central

As observed for many types of cancers, heritable variants of ultraviolet light-induced tumors often grow more aggressively than the parental tumors. The aggressive growth of some variants is due to the loss of a T cell-recognized tumor-specific antigen; however, other variants retain such antigens. We have analyzed an antigen retention variant and found that the variant tumor cells grow at the same rate as the parental tumor cells in vitro, but grew more rapidly than the parental cells in the T cell-deficient host. The growth of the variant cells was stimulated in vitro by factors released from tumor-induced leukocytes and by several defined growth factors. In addition, the variant cancer cells actually attracted more leukocytes in vitro than the parental cells. Furthermore, elimination of granulocytes in vivo in nude mice by a specific antigranulocyte antibody inhibited the growth of the variant cancer, indicating that this tumor requires granulocytes for rapid growth. PMID:7807024

1995-01-01

161

Effect of defaunation and amino acid supplementation on growth and amino acid balance in growing sheep  

E-print Network

Effect of defaunation and amino acid supplementation on growth and amino acid balance in growing, and the wool growth. The supplementation with protected amino acids may increase the growth rate and may lead and the addition of protected methionine and lysine on animal growth and amino acids digestibility in the body

Paris-Sud XI, Université de

162

Running Head: Amino acid inhibition of Agrp gene expression  

E-print Network

Metabolic fuels act on hypothalamic neurons to regulate feeding behavior and energy homeostasis, but the signaling mechanisms mediating these effects are not fully clear. Rats placed on a low protein diet (10 % of calories) exhibited increased food intake (P amino acid mixture (RPMI 1640) or leucine alone (1 ug) suppressed 24h food intake (P amino acids concentrations within the brain is sufficient to suppress food intake. To define a cellular mechanism for these direct effects, GT1-7 hypothalamic cells were exposed to low amino acids for 16hrs. Decreasing amino acid availability increased Agrp mRNA levels in GT1-7 cells (P amino acid leucine (P amino acid concentrations increased S6K phosphorylation via a rapamycin-sensitive mechanism, suggesting that amino acids directly stimulated mTOR signaling. To test whether mTOR signaling contributes to amino acid inhibition of Agrp gene expression, GT1-7 cells cultured in either low or high amino acids for 16hrs and were also treated with rapamcyin (50 nM). Rapamycin treatment increased Agrp mRNA levels in cells exposed to high amino acids (P = 0.01). Taken together, these observations indicate that amino

Christopher D. Morrison; Xiaochun Xi; Christy L. White; Jianping Ye; Roy J. Martin; Neurosignaling Laboratory; Roy J Martin

163

Apicoplast-Targeting Antibacterials Inhibit the Growth of Babesia Parasites  

PubMed Central

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

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

164

Transfection of the mullerian inhibiting substance gene inhibits local and metastatic tumor-growth.  

PubMed

Mullerian Inhibiting Substance (MIS), a gonadal growth factor important in sexual differentiation, has antiproliferative activity against several human carcinoma cell lines. In this study, we examine the effect of MIS-transfection on the growth characteristics of Chinese hamster ovary (CHO) and human ocular melanoma (OM431) cells, compared to wild-type lines and a CHO line transfected with a noncleavable, inactive MIS mutant. MIS-transfection inhibited proliferation of CHO cells in double-layer agarose, tumor spheroid, and murine subrenal capsule assays, as well as growth of CHO and OM431 cells in pulmonary metastasis studies. These results anticipate further study of targeted gene therapy of certain human tumors with MIS gene constructs. PMID:21573527

Boveri, J; Parry, R; Ruffin, W; Gustafson, M; Lee, K; He, W; Donahoe, P

1993-02-01

165

Vitamins A & D Inhibit the Growth of Mycobacteria in Radiometric Culture  

PubMed Central

Background The role of vitamins in the combat of disease is usually conceptualized as acting by modulating the immune response of an infected, eukaryotic host. We hypothesized that some vitamins may directly influence the growth of prokaryotes, particularly mycobacteria. Methods The effect of four fat-soluble vitamins was studied in radiometric Bactec® culture. The vitamins were A (including a precursor and three metabolites,) D, E and K. We evaluated eight strains of three mycobacterial species (four of M. avium subspecies paratuberculosis (MAP), two of M. avium and two of M. tb. complex). Principal Findings Vitamins A and D cause dose-dependent inhibition of all three mycobacterial species studied. Vitamin A is consistently more inhibitory than vitamin D. The vitamin A precursor, ?-carotene, is not inhibitory, whereas three vitamin A metabolites cause inhibition. Vitamin K has no effect. Vitamin E causes negligible inhibition in a single strain. Significance We show that vitamin A, its metabolites Retinyl acetate, Retinoic acid and 13-cis Retinoic acid and vitamin D directly inhibit mycobacterial growth in culture. These data are compatible with the hypothesis that complementing the immune response of multicellular organisms, vitamins A and D may have heretofore unproven, unrecognized, independent and probable synergistic, direct antimycobacterial inhibitory activity. PMID:22235314

Greenstein, Robert J.; Su, Liya; Brown, Sheldon T.

2012-01-01

166

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

PubMed Central

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.

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

2015-01-01

167

Growth inhibition of Mycobacterium smegmatis by mycobacteriophage-derived enzymes.  

PubMed

We report the ability of mycobacteriophage-derived endolysins to inhibit the growth of Mycobacterium smegmatis. We expressed and purified LysB from mycobacteriophage Bxz2 and compared its activity with that of a previously reported LysB from mycobacteriophage Ms6. The esterase activity of Bxz2 LysB with pNP esters was 10-fold higher than that of the previously reported LysB but its lipolytic activity was significantly lower. The presence of surfactant - Tween 80 or Triton X-100 - significantly increased the activity of LysB. Characterization of LysB-treated M. smegmatis cells and LysB-treated purified cell wall by mass spectroscopy confirmed the hydrolytic activity of the enzyme. Both enzymes were equally effective in inhibiting the growth of M. smegmatis, demonstrating their potential as bacteriostatic agents. PMID:25039052

Grover, Navdeep; Paskaleva, Elena E; Mehta, Krunal K; Dordick, Jonathan S; Kane, Ravi S

2014-09-01

168

Systemic Par-4 inhibits non-autochthonous tumor growth  

PubMed Central

The tumor suppressor protein Par-4 (prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SAC domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SAC has not been validated in animal models. We show that Par-4/SAC-transgenic mice express systemic Par-4/SAC protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SAC pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SAC protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SAC is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy. PMID:21613819

Brandon, Jason; Qiu, Shirley; Shelton, Brent J; Spear, Brett; Bondada, Subbarao; Bryson, Scott

2011-01-01

169

Hydroxyapatite-binding peptides for bone growth and inhibition  

DOEpatents

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.

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

2011-09-20

170

Potent inhibition of ribonuclease A by oligo(vinylsulfonic acid).  

PubMed

Ribonuclease A (RNase A) can make multiple contacts with an RNA substrate. In particular, the enzymatic active site and adjacent subsites bind sequential phosphoryl groups in the RNA backbone through Coulombic interactions. Here, oligomers of vinylsulfonic acid (OVS) are shown to be potent inhibitors of RNase A that exploit these interactions. Inhibition is competitive with substrate and has Ki = 11 pm in assays at low salt concentration. The effect of salt concentration on inhibition indicates that nearly eight favorable Coulombic interactions occur in the RNase A.OVS complex. The phosphonic acid and sulfuric acid analogs of OVS are also potent inhibitors although slightly less effective. OVS is also shown to be a contaminant of MES and other buffers that contain sulfonylethyl groups. Oligomers greater than nine units in length can be isolated from commercial MES buffer. Inhibition by contaminating OVS is responsible for the apparent decrease in catalytic activity that has been observed in assays of RNase A at low salt concentration. Thus, OVS is both a useful inhibitor of RNase A and a potential bane to chemists and biochemists who use ethanesulfonic acid buffers. PMID:12649287

Smith, Bryan D; Soellner, Matthew B; Raines, Ronald T

2003-06-01

171

Growth Inhibition of Pathogenic Bacteria by Sulfonylurea Herbicides  

PubMed Central

Emerging resistance to current antibiotics raises the need for new microbial drug targets. We show that targeting branched-chain amino acid (BCAA) biosynthesis using sulfonylurea herbicides, which inhibit the BCAA biosynthetic enzyme acetohydroxyacid synthase (AHAS), can exert bacteriostatic effects on several pathogenic bacteria, including Burkholderia pseudomallei, Pseudomonas aeruginosa, and Acinetobacter baumannii. Our results suggest that targeting biosynthetic enzymes like AHAS, which are lacking in humans, could represent a promising antimicrobial drug strategy. PMID:23263008

Kreisberg, Jason F.; Ong, Nicholas T.; Krishna, Aishwarya; Joseph, Thomas L.; Wang, Jing; Ong, Catherine; Ooi, Hui Ann; Sung, Julie C.; Siew, Chern Chiang; Chang, Grace C.; Biot, Fabrice; Cuccui, Jon; Wren, Brendan W.; Chan, Joey; Sivalingam, Suppiah P.; Zhang, Lian-Hui; Verma, Chandra

2013-01-01

172

Oral Everolimus Inhibits In-Stent Neointimal Growth  

Microsoft Academic Search

Background—Rapamycin (sirolimus)-eluting stents are associated with reduced restenosis rates in animal studies and initial human trials. The present study evaluated whether orally administered everolimus (a macrolide of the same family as sirolimus) inhibits in-stent neointimal growth in rabbit iliac arteries. Methods and Results—New Zealand white rabbits were randomized to everolimus 1.5 mg\\/kg per day starting 3 days before stenting and

Andrew Farb; Michael John; Eduardo Acampado; Frank D. Kolodgie; Margaret Forney Prescott; Renu Virmani

173

Fucoidan Inhibits the Growth of Hepatocellular Carcinoma Independent of Angiogenesis  

PubMed Central

Some sulphated polysaccharides can bind bFGF but are unable to present bFGF to its high-affinity receptors. Fucoidan, a sulphated polysaccharide purified from brown algae, which has been used as an anticancer drug in traditional Chinese medicine for hundreds of years, exhibits a variety of anticancer effects, including the induction of the apoptosis and autophagy of cancer cells, the inhibition of the growth of cancer cells, the induction of angiogenesis, and the improvement of antitumour immunity. Our research shows that fucoidan dose not inhibit the expressions of VEGF, bFGF, IL-8, and heparanase in HCC cells and/or tumour tissues. Moreover, fucoidan exhibited low affinity for bFGF and could not block the binding of bFGF to heparan sulphated. Although fucoidan had no effect on angiogenesis and apoptosis in vivo, this drug significantly inhibited the tumour growth and the expression of PCNA. These results suggest that fucoidan exhibits an anticancer effect in vivo at least partly through inhibition of the proliferation of HCC cells, although it is unable to suppress the angiogenesis induced by HCC. PMID:23737842

Zhu, Cong; Cao, Rui; Zhang, Shuang-Xia; Man, Ya-Nan; Wu, Xiong-Zhi

2013-01-01

174

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

PubMed Central

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

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

175

Effect of fatty acids on the mycelial growth and polysaccharide formation by Ganoderma lucidum in shake flask cultures  

Microsoft Academic Search

Fatty acids were added into the media to investigate their effects on the mycelial growth and polysaccharide formation by Ganoderma lucidum. The experiments were carried out in freely suspended cultures or immobilized cultures using shake flasks. The results indicate that the extent of stimulation or inhibition were associated with the types and levels of fatty acids. Oleic acid at the

Fan-Chiang Yang; Yn-Fuu Ke; Shanq-Shin Kuo

2000-01-01

176

Macrokinetics of magnesium sulfite oxidation inhibited by ascorbic acid.  

PubMed

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

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

2013-08-15

177

Understanding viral neuraminidase inhibition by substituted difluorosialic acids.  

PubMed

Mechanism-based inhibition of influenza neuraminidases by difluorosialic acids (DFSA) is not only rendered highly specific by incorporation of 4-amino or 4-guanidine substituents but also the half-life for reactivation is greatly increased. Measurement of rate constants for spontaneous hydrolysis of a series of such substituted DFSAs reveals, surprisingly, that inherent inductive effects play very little role in this rate reduction and that interactions with the enzyme are more important. PMID:25587931

Weck, S; Robinson, K; Smith, M R; Withers, S G

2015-02-01

178

The non-metabolizable glucose analog D-glucal inhibits aflatoxin biosynthesis and promotes kojic acid production in Aspergillus flavus  

PubMed Central

Background Aflatoxins (AFs) are potent carcinogenic compounds produced by several Aspergillus species, which pose serious threats to human health. As sugar is a preferred carbohydrate source for AF production, we examined the possibility of using sugar analogs to inhibit AF biosynthesis. Results We showed that although D-glucal cannot be utilized by A. flavus as the sole carbohydrate source, it inhibited AF biosynthesis and promoted kojic acid production without affecting mycelial growth when applied to a glucose-containing medium. The inhibition occurred before the production of the first stable intermediate, norsolorinic acid, suggesting a complete inhibition of the AF biosynthetic pathway. Further studies showed that exogenous D-glucal in culture led to reduced accumulation of tricarboxylic acid (TCA) cycle intermediates and reduced glucose consumption, indicating that glycolysis is inhibited. Expression analyses revealed that D-glucal suppressed the expression of AF biosynthetic genes but promoted the expression of kojic acid biosynthetic genes. Conclusions D-glucal as a non-metabolizable glucose analog inhibits the AF biosynthesis pathway by suppressing the expression of AF biosynthetic genes. The inhibition may occur either directly through interfering with glycolysis, or indirectly through reduced oxidative stresses from kojic acid biosynthesis. PMID:24742119

2014-01-01

179

Antigen 85C Inhibition Restricts Mycobacterium tuberculosis Growth through Disruption of Cord Factor Biosynthesis  

PubMed Central

The antigen 85 (Ag85) protein family, consisting of Ag85A, -B, and -C, is vital for Mycobacterium tuberculosis due to its role in cell envelope biogenesis. The mycoloyl transferase activity of these proteins generates trehalose dimycolate (TDM), an envelope lipid essential for M. tuberculosis virulence, and cell wall arabinogalactan-linked mycolic acids. Inhibition of these enzymes through substrate analogs hinders growth of mycobacteria, but a link to mycolic acid synthesis has not been established. In this study, we characterized a novel inhibitor of Ag85C, 2-amino-6-propyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile (I3-AG85). I3-AG85 was isolated from a panel of four inhibitors that exhibited structure- and dose-dependent inhibition of M. tuberculosis division in broth culture. I3-AG85 also inhibited M. tuberculosis survival in infected primary macrophages. Importantly, it displayed an identical MIC against the drug-susceptible H37Rv reference strain and a panel of extensively drug-resistant/multidrug-resistant M. tuberculosis strains. Nuclear magnetic resonance analysis indicated binding of I3-AG85 to Ag85C, similar to its binding to the artificial substrate octylthioglucoside. Quantification of mycolic acid-linked lipids of the M. tuberculosis envelope showed a specific blockade of TDM synthesis. This was accompanied by accumulation of trehalose monomycolate, while the overall mycolic acid abundance remained unchanged. Inhibition of Ag85C activity also disrupted the integrity of the M. tuberculosis envelope. I3-AG85 inhibited the division of and reduced TDM synthesis in an M. tuberculosis strain deficient in Ag85C. Our results indicate that Ag85 proteins are promising targets for novel antimycobacterial drug design. PMID:22290959

Warrier, Thulasi; Tropis, Marielle; Werngren, Jim; Diehl, Anne; Gengenbacher, Martin; Schlegel, Brigitte; Schade, Markus; Oschkinat, Hartmut; Daffe, Mamadou; Hoffner, Sven; Eddine, Ali Nasser

2012-01-01

180

Inhibition by caffeic acid of the influenza A virus multiplication in vitro.  

PubMed

Caffeic acid has been shown to inhibit the multiplication of influenza A virus in vitro, whereas caffeine, quinic acid and chlorogenic acid do not. Caffeic acid has also been shown to have antiviral activity against herpes simplex virus (DNA virus) and polio virus (RNA virus). In the present study, a comparison of the one-step growth curve of the influenza virus in the presence of caffeic acid with that in the absence of the reagent showed that an eclipse period of the virus multiplication in the infected cells was not affected by the reagent, while the progeny virus yield was markedly decreased in the presence of caffeic acid. In additional experiments, it was found that the addition of caffeic acid at an early time point post-infection (within 3 h post-infection) was mandatory for extensive antiviral activity, suggesting that a major target of the reagent exists in the early stages of infection. Simultaneously with the decrease in the progeny virus yield, both the virus-induced cytopathic effects and apoptotic nuclear fragmentation were markedly suppressed by the reagent, suggesting that caffeic acid suppresses, at least temporally, the degeneration of the virus-infected cells and that the observed antiviral activity is likely not the secondary result of the cytotoxic effects of the reagent. These results suggest the potential pharmacological use of caffeic acid or its derivatives as an antiviral drug against influenza A virus. PMID:25050906

Utsunomiya, Hirotoshi; Ichinose, Masao; Ikeda, Keiko; Uozaki, Misao; Morishita, Junko; Kuwahara, Tomomi; Koyama, A Hajime; Yamasaki, Hisashi

2014-10-01

181

Enhancement of taxol-induced apoptosis by inhibition of NF-?B with ursorlic acid  

NASA Astrophysics Data System (ADS)

Taxol is known to inhibit cell growth and triggers significant apoptosis in various cancer cells, and activation of proliferation factor NF-?B during Taxol-induced apoptosis is regarded as a main reason resulting in tumor cells resistance to Taxol. It has been found that ursorlic acid can inhibit the activation of NF-?B. In order to study whether ursorlic acid can enhance the Taxol-induced apoptosis, we use fluorescence resonance energy transfer (FRET) technique and probe SCAT3 to compare the difference of caspase-3 activation between Taxol alone and Taxol combined ursorlic acid. With laser scanning confocal microscopy, we find that ursorlic acid, a nontoxic food component, sensitizes ASTC-a-1 cells more efficiently to Taxol-induced apoptosis by advanced activation of caspase 3. The result also suggests that there would be a synergistic effect between Taxol and ursorlic acid, and the more detailed mechanism of synergistic effect needs to be clarified further, such as the correlations among NF-?B, Akt, caspase 8, which leads to the advanced activation of caspase 3 during combined treatment of Taxol and ursorlic acid. Moreover, this may be a new way to improve Taxol-dependent tumor therapy.

Li, Yunlong; Xing, Da

2007-05-01

182

Fatty acid amide hydrolase inhibition by neurotoxic organophosphorus pesticides.  

PubMed

Organophosphorus (OP) compound-induced inhibition of acetylcholinesterase (AChE) and neuropathy target esterase explains the rapid onset and delayed neurotoxic effects, respectively, for OP insecticides and related compounds but apparently not a third or intermediate syndrome with delayed onset and reduced limb mobility. This investigation tests the hypothesis that fatty acid amide hydrolase (FAAH), a modulator of endogenous signaling compounds affecting sleep (oleamide) and analgesia (anandamide), is a sensitive target for OP pesticides with possible secondary neurotoxicity. Chlorpyrifos oxon inhibits 50% of the FAAH activity (IC50 at 15 min, 25 degrees C, pH 9.0) in vitro at 40--56 nM for mouse brain and liver, whereas methyl arachidonyl phosphonofluoridate, ethyl octylphosphonofluoridate (EOPF), oleyl-4H-1,3,2-benzodioxaphosphorin 2-oxide (oleyl-BDPO), and dodecyl-BDPO give IC50s of 0.08--1.1 nM. These BDPOs and EOPF inhibit mouse brain FAAH in vitro with > or =200-fold higher potency than for AChE. Five OP pesticides inhibit 50% of the brain FAAH activity (ED50) at <30 mg/kg 4 h after ip administration to mice; while inhibition by chlorpyrifos, diazinon, and methamidophos occurs near acutely toxic levels, profenofos and tribufos are effective at asymptomatic doses. Two BDPOs (dodecyl and phenyl) and EOPF are potent inhibitors of FAAH in vivo (ED50 0.5--6 mg/kg). FAAH inhibition of > or =76% in brain depresses movement of mice administered anandamide at 30 mg/kg ip, often leading to limb recumbency. Thus, OP pesticides and related inhibitors of FAAH potentiate the cannabinoid activity of anandamide in mice. More generally, OP compound-induced FAAH inhibition and the associated anandamide accumulation may lead to reduced limb mobility as a secondary neurotoxic effect. PMID:11350214

Quistad, G B; Sparks, S E; Casida, J E

2001-05-15

183

Inhibition of intracranial glioma growth by endometrial regenerative cells.  

PubMed

Animal studies have demonstrated that selective tropism of mesenchymal stem cells (MSC) for glioma may be used as a means of selective delivery of cytotoxic payloads. Endometrial Regenerative Cells (ERC) are a population of mesenchymal-like cells which possesse pluripotent differentiation capacity and is characterized by unique surface markers and growth factor production. In this study we sought to determine whether unmanipulated ERC would alter the growth of glioma using the aggressive C6/LacZ7 (C6) into Sprague Dawley rat model. ERC administration by intravenous (i.v.) or intratumoral (i.t.) showed significant inhibition of glioma: volume reduction of 49% after i.v. treatment (p < 0.05), and about 46% i.t. treatment (p < 0.05). Tumor reduction was associated with inhibition of angiogenesis and reduced numbers of CD133 positive cells in the incranial tumor. Despite the angiogenic potential of ERC in the hindlimb ischemia model, these data support a paradoxical tumor inhibitory activity of ERC. Further studies are needed to determine the qualitative differences between physiological angiogenesis, which seems to be supported by ERC and tumor angiogenesis which appeared to be inhibited. PMID:19197154

Han, Xiaodi; Meng, Xiaolong; Yin, Zhenglian; Rogers, Andrea; Zhong, Jie; Rillema, Paul; Jackson, James A; Ichim, Thomas E; Minev, Boris; Carrier, Ewa; Patel, Amit N; Murphy, Michael P; Min, Wei-Ping; Riordan, Neil H

2009-02-15

184

Effect of retinoids on growth inhibition of two canine melanoma cell lines.  

PubMed

Two new canine melanoma cell lines (CMM1 and CMM2) were established from the patients with oral malignant melanomas. Histopathological type of both CMM1 and CMM2 was a mixed cell type consisted of spindle-shaped cells, polygonal cells, and oval cells. Doubling time of CMMI and CMM2 were 18.4 +/- 1.96 hr and 21.0 +/- 0.73 hr, respectively. The effect of two kinds of retinoids (all-trans retinoic acid and 9-cis retinoic acid) on the proliferation of these cells were examined by morphological changes, proliferation assay and apoptosis assay. However, the retinoids did not suppress growth rate of these cells. This result suggests that retinoids used in this study did not induce differentiation, apoptosis, and growth inhibition of the canine melanoma cell lines. PMID:11217070

Ohashi, E; Hong, S H; Takahashi, T; Nakagawa, T; Mochizuki, M; Nishimura, R; Sasak, N

2001-01-01

185

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

PubMed

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

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

2012-12-01

186

Avian Incubation Inhibits Growth and Diversification of Bacterial Assemblages on Eggs  

E-print Network

Avian Incubation Inhibits Growth and Diversification of Bacterial Assemblages on Eggs Matthew D (2009) Avian Incubation Inhibits Growth and Diversification of Bacterial Assemblages on Eggs. PLoS ONE 4 by limiting microbial growth of pathogenic bacteria on eggshells, while enhancing growth of commensal

Beissinger, Steven R.

187

?-Pinene Inhibits Growth and Induces Oxidative Stress in Roots  

PubMed Central

• 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

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

2006-01-01

188

Cadmium inhibits acid secretion in stimulated frog gastric mucosa  

SciTech Connect

Cadmium, a toxic environmental pollutant, affects the function of different organs such as lungs, liver and kidney. Less is known about its toxic effects on the gastric mucosa. The aim of this study was to investigate the mechanisms by which cadmium impacts on the physiology of gastric mucosa. To this end, intact amphibian mucosae were mounted in Ussing chambers and the rate of acid secretion, short circuit current (I{sub sc}), transepithelial potential (V{sub t}) and resistance (R{sub t}) were recorded in the continuous presence of cadmium. Addition of cadmium (20 {mu}M to 1 mM) on the serosal but not luminal side of the mucosae resulted in inhibition of acid secretion and increase in NPPB-sensitive, chloride-dependent short circuit current. Remarkably, cadmium exerted its effects only on histamine-stimulated tissues. Experiments with TPEN, a cell-permeant chelator for heavy metals, showed that cadmium acts from the intracellular side of the acid secreting cells. Furthermore, cadmium-induced inhibition of acid secretion and increase in I{sub sc} cannot be explained by an action on: 1) H{sub 2} histamine receptor, 2) Ca{sup 2+} signalling 3) adenylyl cyclase or 4) carbonic anhydrase. Conversely, cadmium was ineffective in the presence of the H{sup +}/K{sup +}-ATPase blocker omeprazole suggesting that the two compounds likely act on the same target. Our findings suggest that cadmium affects the functionality of histamine-stimulated gastric mucosa by inhibiting the H{sup +}/K{sup +}-ATPase from the intracellular side. These data shed new light on the toxic effect of this dangerous environmental pollutant and may result in new avenues for therapeutic intervention in acute and chronic intoxication.

Gerbino, Andrea, E-mail: gerbino@biologia.uniba.i [Dept. of General and Environmental Physiology, University of Bari, 70126 Bari (Italy); Debellis, Lucantonio; Caroppo, Rosa [Dept. of General and Environmental Physiology, University of Bari, 70126 Bari (Italy); Curci, Silvana [VA Boston Healthcare System and the Department of Surgery, Harvard Medical School, and Brigham and Women's Hospital, 1400 VFW Parkway, West Roxbury MA 02132 (United States); Colella, Matilde [Dept. of General and Environmental Physiology, University of Bari, 70126 Bari (Italy)

2010-06-01

189

Catechin-incorporated dental copolymers inhibit growth of Streptococcus mutans  

PubMed Central

Objective: To test the inhibitory growth activity of green tea catechin incorporated into dental resins compared to resins containing the broad-spectrum antimicrobial compound chlorhexidine against Streptococcus mutans in vitro. Material and Methods: The minimum inhibitory concentrations (MICs) of epigallocatechin-gallate (EGCg) and chlorhexidine (CHX) were determined according to the microdilution method. Resin discs (5 mm x 3 mm) were prepared from Bis-GMA/TEGDMA (R1) and Bis-GMA/CH3Bis-GMA (R2) comonomers (n=9) containing: a) no drug, b) EGCg, c) CHX. Two concentrations of each drug (0.5x MIC and 1x MIC) were incorporated into the resin discs. Samples were individually immersed in a bacterial culture and incubated for 24 h at 37º C under constant agitation. Cell viability was assessed by counting the number of colonies on replica agar plates. Statistical analysis was performed using one-way ANOVA, Tukey and Student t-tests (?=0.05). Results: Both resins containing EGCg and CHX showed a significant inhibition of bacterial growth at both concentrations tested (p<0.05). A significantly higher inhibition was observed in response to resins containing CHX at 0.5x MIC and 1x MIC, and EGCg at 1x MIC when compared to EGCg at 0.5x MIC. Also, EGCg at 0.5x MIC in R1 had a significantly higher growth inhibition than in R2. Conclusions: Both EGCg and CHX retained their antibacterial activity when incorporated into the resin matrix. EGCg at 1x MIC in R1 and R2 resins significantly reduced S. mutans survival at a level similar to CHX. The data generated from this study will provide advances in the field of bioactive dental materials with the potential of improving the lifespan of resin-based restorations. PMID:23739855

MANKOVSKAIA, Alexandra; LÉVESQUE, Céline M.; PRAKKI, Anuradha

2013-01-01

190

Androgen receptor coactivators that inhibit prostate cancer growth  

PubMed Central

It is well documented that androgen receptor (AR), a steroid hormone receptor, is important for prostate cancer (PCa) growth. Conversely, however, there is increasing evidence that activation of AR by androgens can also lead to growth suppression in prostate cells. AR mediated transcription is regulated by a number of different transcriptional coactivators. Changes in expression level or cellular localization of specific coactivators may play a crucial role in this switch between proliferative and anti- proliferative processes regulated by AR target gene programs. In this review, we discuss the expression and function of several AR coactivators exhibiting growth suppressive function in PCa, including ARA70/ELE1/NCOA4, androgen receptor coactivator p44/MEP50/WDR77, TBLR1, and ART-27. In luciferase reporter assays, they all have been shown to activate AR mediated transcriptional activation. ARA70 exists in two forms, the full length nuclear ARA70? and internally spliced cytoplasmic ARA70?. For p44 and TBLR1, we identified nuclear and cytoplasmic forms with distinct expression and function. In comparison of their expression (ARA70?, p44, TBLR1 and ART-27) in prostate, these coactivators are expressed in the nucleus of benign prostate epithelial cells while they are more predominantly expressed in cytoplasmic form (ARA70?, cytoplasmic p44 and TBLR1) in PCa. Consistent with their nuclear expression in benign prostate, the nuclear form of these coactivators inhibit PCa growth targeting a subset of AR target genes. In contrast, the cytoplasmic versions of these proteins enhance PCa growth and invasion. Interestingly, first characterized as an AR coactivator in luciferase assays, ART-27 functions as corepressor for endogenous AR target genes. Importantly, the growth inhibitions by these nuclear proteins are androgen-dependent processes and the regulation of invasion is androgen-independent. Understanding the molecular switches involved in the transition from AR dependent growth promotion to growth suppression and dysregulation of these coactivator proteins promoting androgen-independent invasion may lead to identification of novel therapeutic targets for PCa. PMID:25374906

Daniels, Garrett; Jha, Ruchi; Shen, Ying; Logan, Susan K; Lee, Peng

2014-01-01

191

Tranexamic acid concentrations associated with human seizures inhibit glycine receptors  

PubMed Central

Antifibrinolytic drugs are widely used to reduce blood loss during surgery. One serious adverse effect of these drugs is convulsive seizures; however, the mechanisms underlying such seizures remain poorly understood. The antifibrinolytic drugs tranexamic acid (TXA) and ?-aminocaproic acid (EACA) are structurally similar to the inhibitory neurotransmitter glycine. Since reduced function of glycine receptors causes seizures, we hypothesized that TXA and EACA inhibit the activity of glycine receptors. Here we demonstrate that TXA and EACA are competitive antagonists of glycine receptors in mice. We also showed that the general anesthetic isoflurane, and to a lesser extent propofol, reverses TXA inhibition of glycine receptor–mediated current, suggesting that these drugs could potentially be used to treat TXA-induced seizures. Finally, we measured the concentration of TXA in the cerebrospinal fluid (CSF) of patients undergoing major cardiovascular surgery. Surprisingly, peak TXA concentration in the CSF occurred after termination of drug infusion and in one patient coincided with the onset of seizures. Collectively, these results show that concentrations of TXA equivalent to those measured in the CSF of patients inhibited glycine receptors. Furthermore, isoflurane or propofol may prevent or reverse TXA-induced seizures. PMID:23187124

Lecker, Irene; Wang, Dian-Shi; Romaschin, Alexander D.; Peterson, Mark; Mazer, C. David; Orser, Beverley A.

2012-01-01

192

Streptococcus mutans inhibits Candida albicans hyphal formation by the fatty acid signaling molecule trans-2-decenoic acid (SDSF).  

PubMed

In the human mouth, fungi and several hundred species of bacteria coexist. Here we report a case of interkingdom signaling in the oral cavity: A compound excreted by the caries bacterium Streptococcus mutans inhibits the morphological transition from yeast to hyphae, an important virulence trait, in the opportunistic fungus Candida albicans. The compound excreted by S. mutans was originally studied because it inhibited signaling by the universal bacterial signal autoinducer-2 (AI-2), determined by the luminescence of a Vibrio harveyi sensor strain. The inhibitor was purified from cell-free culture supernatants of S. mutans guided by its activity. Its chemical structure was elucidated by using NMR spectroscopy and GC-MS and proved to be trans-2-decenoic acid. We show that trans-2-decenoic acid does not inhibit AI-2-specific signaling, but rather the luciferase reaction used for its detection. A potential biological role of trans-2-decenoic acid was then discovered. It is able to suppress the transition from yeast to hyphal morphology in the opportunistic human pathogen Candida albicans at concentrations that do not affect growth. The expression of HWP1, a hyphal-specific signature gene of C. albicans, is abolished by trans-2-decenoic acid. trans-2-Decenoic acid is structurally similar to the diffusible signal factor (DSF) family of interkingdom-signaling molecules and is the first member of this family from a Gram-positive organism (Streptococcus DSF, SDSF). SDSF activity was also found in S. mitis, S. oralis, and S. sanguinis, but not in other oral bacteria. SDSF could be relevant in shaping multispecies Candida bacteria biofilms in the human body. PMID:20572249

Vílchez, Ramiro; Lemme, André; Ballhausen, Britta; Thiel, Verena; Schulz, Stefan; Jansen, Rolf; Sztajer, Helena; Wagner-Döbler, Irene

2010-07-26

193

Insulin-like Growth Factor Binding Protein-4 Differentially Inhibits Growth Factor-induced Angiogenesis*  

PubMed Central

An in-depth understanding of the molecular and cellular complexity of angiogenesis continues to advance as new stimulators and inhibitors of blood vessel formation are uncovered. Gaining a more complete understanding of the response of blood vessels to both stimulatory and inhibitory molecules will likely contribute to more effective strategies to control pathological angiogenesis. Here, we provide evidence that endothelial cell interactions with structurally altered collagen type IV may suppress the expression of insulin-like growth factor binding protein-4 (IGFBP-4), a well documented inhibitor of the IGF-1/IGF-1R signaling axis. We report for the first time that IGFBP-4 differentially inhibits angiogenesis induced by distinct growth factor signaling pathways as IGFBP-4 inhibited FGF-2- and IGF-1-stimulated angiogenesis but failed to inhibit VEGF-induced angiogenesis. The resistance of VEGF-stimulated angiogenesis to IGFBP-4 inhibition appears to depend on sustained activation of p38 MAPK as blocking its activity restored the anti-angiogenic effects of IGFBP-4 on VEGF-induced blood vessel growth in vivo. These novel findings provide new insight into how blood vessels respond to endogenous inhibitors during angiogenesis stimulated by distinct growth factor signaling pathways. PMID:22134921

Contois, Liangru W.; Nugent, Desiree P.; Caron, Jennifer M.; Cretu, Alexandra; Tweedie, Eric; Akalu, Abebe; Liebes, Leonard; Friesel, Robert; Rosen, Clifford; Vary, Calvin; Brooks, Peter C.

2012-01-01

194

Selective Inhibition of Auxin-Stimulated NADH Oxidase Activity and Elongation Growth of Soybean Hypocotyls by Thiol Reagents.  

PubMed Central

The NADH oxidase activity of isolated vesicles of soybean (Glycine max cv Williams 82) plasma membranes and elongation growth of 1-cm-long hypocotyl segments were stimulated by auxins (indole-3-acetic acid or 2,4-dichlorophenoxyacetic acid [2,4-D]). The auxin-induced stimulations of both NADH oxidase and growth were prevented by the thiol reagents N-ethylmaleimide, p-chloromercuribenzoate, 5,5[prime]-dithiobis(2-nitrophenylbenzoic acid), dithiothreitol, and reduced glutathione. These same reagents largely were without effect on or stimulated slightly the basal levels of NADH oxidase and growth when assayed in the absence of auxins. In the presence of dithiothreitol or reduced glutathione, both 2,4-D and indole-3-acetic acid either failed to stimulate or inhibited the NADH oxidase activity. The rapidity of the response at a given concentration of thiol reagent and the degree of inhibition of the 2,4-D-induced NADH oxidase activity were dependent on order of reagent addition. If the thiol reagents were added first, auxin stimulations were prevented. If auxins were added first, the inhibitions by the thiol reagents were delayed or higher concentrations of thiol reagents were required to achieve inhibition. The results demonstrate a fundamental difference between the auxin-stimulated and the constitutive NADH oxidase activities of soybean plasma membranes that suggest an involvement of active-site thiols in the auxin-stimulated but not in the constitutive activity. PMID:12228435

Morre, D. J.; Brightman, A. O.; Hidalgo, A.; Navas, P.

1995-01-01

195

Inhibition of melanoma tumor growth in vivo by survivin targeting.  

PubMed

A role of apoptosis (programmed cell death) in tumor formation and growth was investigated by targeting the apoptosis inhibitor survivin in vivo. Expression of a phosphorylation-defective survivin mutant (Thr(34)-->Ala) triggered apoptosis in several human melanoma cell lines and enhanced cell death induced by the chemotherapeutic drug cisplatin in vitro. Conditional expression of survivin Thr(34)-->Ala in YUSAC2 melanoma cells prevented tumor formation upon s.c. injection into CB.17 severe combined immunodeficient-beige mice. When induced in established melanoma tumors, survivin Thr(34)-->Ala inhibited tumor growth by 60-70% and caused increased apoptosis and reduced proliferation of melanoma cells in vivo. Manipulation of the antiapoptotic pathway maintained by survivin may be beneficial for cancer therapy. PMID:11149963

Grossman, D; Kim, P J; Schechner, J S; Altieri, D C

2001-01-16

196

Inhibition of melanoma tumor growth in vivo by survivin targeting  

PubMed Central

A role of apoptosis (programmed cell death) in tumor formation and growth was investigated by targeting the apoptosis inhibitor survivin in vivo. Expression of a phosphorylation-defective survivin mutant (Thr34?Ala) triggered apoptosis in several human melanoma cell lines and enhanced cell death induced by the chemotherapeutic drug cisplatin in vitro. Conditional expression of survivin Thr34?Ala in YUSAC2 melanoma cells prevented tumor formation upon s.c. injection into CB.17 severe combined immunodeficient-beige mice. When induced in established melanoma tumors, survivin Thr34?Ala inhibited tumor growth by 60–70% and caused increased apoptosis and reduced proliferation of melanoma cells in vivo. Manipulation of the antiapoptotic pathway maintained by survivin may be beneficial for cancer therapy. PMID:11149963

Grossman, Douglas; Kim, Paul J.; Schechner, Jeffrey S.; Altieri, Dario C.

2001-01-01

197

Inhibition of C4 photosynthesis by (benzamidooxy)acetic acid.  

PubMed

(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

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

1982-12-01

198

Inhibition of Virus Growth by Ouabain: Effect of Ouabain on the Growth of HVJ in Chick Embryo Cells  

PubMed Central

The effect of ouabain (g-strophanthin), a cardiac glycoside, on the growth of several enveloped viruses was examined. It was found that the growth of HVJ (Sendai virus) in chick embryo cells was markedly inhibited by the drug at a concentration as low as 5 × 10?5m. A virus-inhibitory concentration of ouabain did not cause morphological changes in uninfected cells, nor did it have the capacity to inactivate virus infectivity. Ouabain interfered with the intracellular synthesis of viral macromolecules. Although viral ribonucleic acid and viral antigens were synthesized by the ouabain-treated cells, the rate of synthesis was slower, and the total amounts of these macromolecules were smaller than those in the untreated control cells. It is suggested that ouabain inhibits the function of membrane-bound Na, K-adenosine triphosphatase of the chick embryo cells and thus prevents accumulation of K ion in them. Accumulation of intracellular K ion to a certain level would be needed for events of exponential growth of virus to proceed, and ouabain might inhibit this step by preventing such accumulation of K ion. This view was supported by the finding that the concentration of K ion in the HVJ-infected cells was rapidly reduced by the treatment with ouabain, and that, when the ouabain-treated culture was shifted to a medium containing a higher concentration of K ion than normal medium, virus production started in parallel with the increase of intracellular K ion. The fact that the concentration of K ion in BHK-21 cells, which support virus growth in the presence of ouabain, is not reduced by the treatment with the drug also suggested this possibility. Images PMID:4335518

Nagai, Yoshiyuki; Maeno, Koichiro; Iinuma, Masao; Yoshida, Tetsuya; Matsumoto, Toshisada

1972-01-01

199

Mo polyoxometalate nanoparticles inhibit tumor growth and vascular endothelial growth factor induced angiogenesis  

NASA Astrophysics Data System (ADS)

Tumor growth depends on angiogenesis, which can furnish the oxygen and nutrients that proliferate tumor cells. Thus, blocking angiogenesis can be an effective strategy to inhibit tumor growth. In this work, three typical nanoparticles based on polyoxometalates (POMs) have been prepared; we investigated their capability as antitumor and anti-angiogenesis agents. We found that Mo POM nanoparticles, especially complex 3, inhibited the growth of human hepatocellular liver carcinoma cells (HepG2) through cellular reactive oxygen species levels’ elevation and mitochondrial membrane potential damage. Complex 3 also suppressed the proliferation, migration, and tube formation of endothelial cells in vitro and chicken chorioallantoic membrane development ex vivo. Furthermore, western blot analysis of cell signaling molecules indicated that Mo POMs blocked the vascular endothelial growth factor receptor 2-mediated ERK1/2 and AKT signaling pathways in endothelial cells. Using transmission electron microscopy, we demonstrated their cellular uptake and localization within the cytoplasm of HepG2 cells. These results indicate that, owing to the extraordinary physical and chemical properties, Mo POM nanoparticles can significantly inhibit tumor growth and angiogenesis, which makes them potential drug candidates in anticancer and anti-angiogenesis therapies.

Zheng, Wenjing; Yang, Licong; Liu, Ying; Qin, Xiuying; Zhou, Yanhui; Zhou, Yunshan; Liu, Jie

2014-06-01

200

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

Microsoft Academic Search

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

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

1984-01-01

201

Hypothiocyanous acid oxidation of tubulin cysteines inhibits microtubule polymerization  

PubMed Central

Thiol oxidation is a probable outcome of cellular oxidative stress and is linked to degenerative disease progression. In addition, protein thiol redox reactions are increasingly identified as a mechanism to regulate protein structure and function. We assessed the effect of hypothiocyanous acid on the cytoskeletal protein tubulin. Total cysteine oxidation by hypothiocyanous and hypochlorous acids was monitored by labeling tubulin with 5-iodoacetamidofluorescein and by detecting higher molecular weight inter-chain tubulin disulfides by Western blot under nonreducing conditions. Hypothiocyanous acid induced nearly stoichiometric oxidation of tubulin cysteines (1.9 mol cysteine/mol oxidant) and no methionine oxidation was observed. Because disulfide reducing agents restored all the polymerization activity that was lost due to oxidant treatment, we conclude that cysteine oxidation of tubulin inhibits microtubule polymerization. Hypothiocyanous acid oxidation of tubulin cysteines was markedly decreased in the presence of 4% glycerol, a component of the tubulin purification buffer. Due to its instability and buffer- and pH-dependent reactivity, hypothiocyanous acid studies require careful consideration of reaction conditions. PMID:24215946

Clark, Hillary M.; Hagedorn, Tara D.; Landino, Lisa M.

2013-01-01

202

Inhibition of Angiogenesis In Vitro by Chebulagic Acid: A COX-LOX Dual Inhibitor  

PubMed Central

Angiogenesis is a crucial step in the growth of cancer and its metastasis. It is regulated by several endogenous factors which may stimulate or inhibit the new blood vessel growth. Besides these endogenous factors, several exogenous factors including some natural compounds are known to modulate angiogenesis. Angiogenesis being a potential target for drugs against a number of pathological conditions, search for compounds from natural sources that can affect angiogenesis is of great interest. The objective of our present study was to understand the effect of chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., on angiogenesis. The model systems used were rat aortic rings and human umbilical vein endothelial cells. The results showed that chebulagic acid exerts an antiangiogenic effect. This was evidenced from decreased sprouting in rat aortic rings and decrease in biochemical markers in endothelial cells treated with chebulagic acid. It downregulated the production of CD31, E-selectin, and vascular endothelial growth factor in human umbilical vein endothelial cells in culture (HUVEC). Further studies to understand the molecular mechanism of action of chebulagic acid revealed that CA exerts its anti angiogenic effect by modulating VE cadherin-? catenin signalling in human umbilical vein endothelial cells. PMID:24288615

Athira, A. P.; Helen, A.; Saja, K.; Reddanna, P.; Sudhakaran, P. R.

2013-01-01

203

Humic and fulvic acids stimulate the growth of Mycobacterium avium  

E-print Network

Humic and fulvic acids stimulate the growth of Mycobacterium avium Richard A. Kirschner Jr. 1 are similar in that they are rich in humic and fulvic acids and of low pH and dissolved oxygen. Growth to their ability to proliferate in those humic- and fulvic-rich, acidic, micro-aerobic environments. Ã? 1999

Falkinham, Joseph

204

Hypernegative Supercoiling Inhibits Growth by Causing RNA Degradation?  

PubMed Central

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

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

2008-01-01

205

Inhibition of human neutrophil degranulation by transforming growth factor-?1  

PubMed Central

Neutrophils enter tissues including the uterus and are found in the endometrium in increased numbers prior to menses. In this environment, they are exposed to transforming growth factor (TGF)-?1 produced by endometrial stromal and epithelial cells. We observed that incubation of neutrophils in vitro with TGF-?1 at 1 pg/ml significantly reduced their secretion of lactoferrin in response to lipopolysaccharide (LPS). This effect was achieved with as little as 15 min of pretreatment with TGF-?1. Inhibition of lactoferrin release by TGF-?1 was observed irrespective of whether neutrophils were stimulated by ligands for Toll-like receptor (TLR)-2, TLR-4 or FPR, the G protein-coupled receptor for formylated peptides. Inhibition by TGF-?1 was negated by SB-431542, a small molecule inhibitor that specifically blocks the kinase activity of the type I TGF-? receptor (ALK5) In contrast to lactoferrin release, another important neutrophil function, interleukin (IL)-8 driven chemotaxis, was not affected by TGF-?1 at 1 pg/ml or 100 pg/ml. We conclude that in tissues of the female reproductive tract, TGF-?1 inhibition of neutrophil degranulation may prevent these cells from initiating an inflammatory response or releasing degradative enzymes that could potentially damage the oocyte or fetus. PMID:17403059

Shen, L; Smith, J M; Shen, Z; Eriksson, M; Sentman, C; Wira, C R

2007-01-01

206

Production of gluconic acid from glucose by Aspergillus niger: growth and non-growth conditions  

Microsoft Academic Search

Batch fermentation of glucose to gluconic acid was conducted using Aspergillus niger under growth and non-growth conditions using pure oxygen and air as a source of oxygen for the fermentation in 2 and 5l stirred tank reactors (batch reactor). Production of gluconic acid under growth conditions was conducted in a 5l batch reactor. Production and growth rates were higher during

H. Znad; J. Markoš; V. Baleš

2004-01-01

207

Boswellic acid inhibits inflammatory angiogenesis in a murine sponge model  

Microsoft Academic Search

The aim of the present study was to investigate the effects of boswellic acid (BA) on key components of inflammatory angiogenesis in the murine cannulated sponge implant angiogenesis model. Polyester–polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and BA (12.5 or 25mg\\/kg\\/day) was given through installed cannulas for nine days. The implants

Sarita Saraswati; Maneesha Pandey; Rajani Mathur; S. S. Agrawal

2011-01-01

208

Sanguinarine Suppresses Prostate Tumor Growth and Inhibits Survivin Expression  

PubMed Central

Prostate cancer is a frequently occurring disease and is the second leading cause of cancer-related deaths of men in the United States. Current treatments have proved inadequate in curing or controlling prostate cancer, and a search for agents for the management of this disease is urgently needed. Survivin plays an important role in both progression of castration-resistant prostate cancer and resistance to chemotherapy. Altered expression of survivin in prostate cancer cells is associated with cancer progression, drug/radiation resistance, poor prognosis, and short patient survival. In the present study, the authors performed a cell-based rapid screen of the Prestwick Chemical Library consisting of 1120 Food and Drug Administration–approved compounds with known safety and bioavailability in humans to identify potential inhibitors of survivin and anticancer agents for prostate cancer. Sanguinarine, a benzophenanthridine alkaloid derived primarily from the bloodroot plant, was identified as a novel inhibitor of survivin that selectively kills prostate cancer cells over “normal” prostate epithelial cells. The authors found that sanguinarine inhibits survivin protein expression through protein degradation via the ubiquitin-proteasome system. Sanguinarine induces apoptosis and inhibits growth of human prostate cancer cells and in vivo tumor formation. Administration of sanguinarine, beginning 3 days after ectopic implantation of DU145 human prostate cancer cells, reduces both tumor weight and volume. In addition, sanguinarine sensitized paclitaxel-mediated growth inhibition and apoptosis, offering a potential therapeutic strategy for overcoming taxol resistance. These results suggest that sanguinarine may be developed as an agent either alone or in combination with taxol for treatment of prostate cancer overexpressing survivin. PMID:21318089

Sun, Meng; Lou, Wei; Chun, Jae Yeon; Cho, Daniel S.; Nadiminty, Nagalakshmi; Evans, Christopher P.; Chen, Jun; Yue, Jiao; Zhou, Qinghua; Gao, Allen C.

2010-01-01

209

Sanguinarine suppresses prostate tumor growth and inhibits survivin expression.  

PubMed

Prostate cancer is a frequently occurring disease and is the second leading cause of cancer-related deaths of men in the United States. Current treatments have proved inadequate in curing or controlling prostate cancer, and a search for agents for the management of this disease is urgently needed. Survivin plays an important role in both progression of castration-resistant prostate cancer and resistance to chemotherapy. Altered expression of survivin in prostate cancer cells is associated with cancer progression, drug/radiation resistance, poor prognosis, and short patient survival. In the present study, the authors performed a cell-based rapid screen of the Prestwick Chemical Library consisting of 1120 Food and Drug Administration-approved compounds with known safety and bioavailability in humans to identify potential inhibitors of survivin and anticancer agents for prostate cancer. Sanguinarine, a benzophenanthridine alkaloid derived primarily from the bloodroot plant, was identified as a novel inhibitor of survivin that selectively kills prostate cancer cells over "normal" prostate epithelial cells. The authors found that sanguinarine inhibits survivin protein expression through protein degradation via the ubiquitin-proteasome system. Sanguinarine induces apoptosis and inhibits growth of human prostate cancer cells and in vivo tumor formation. Administration of sanguinarine, beginning 3 days after ectopic implantation of DU145 human prostate cancer cells, reduces both tumor weight and volume. In addition, sanguinarine sensitized paclitaxel-mediated growth inhibition and apoptosis, offering a potential therapeutic strategy for overcoming taxol resistance. These results suggest that sanguinarine may be developed as an agent either alone or in combination with taxol for treatment of prostate cancer overexpressing survivin. PMID:21318089

Sun, Meng; Lou, Wei; Chun, Jae Yeon; Cho, Daniel S; Nadiminty, Nagalakshmi; Evans, Christopher P; Chen, Jun; Yue, Jiao; Zhou, Qinghua; Gao, Allen C

2010-03-01

210

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

PubMed Central

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

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

2014-01-01

211

Specificity of growth inhibition of melanoma by 4-hydroxyanisole.  

PubMed

An experimental study using human melanoma (NEL-MI), rat hepatoma (Fu5-5), and human kidney (293-31) cell lines was undertaken in order to evaluate the antitumor activity of 4-hydroxyanisole (4-OHA) in vitro. Prior reports have indicated highly specific antitumor activity of 4-OHA against melanoma cells in vitro. This specific antitumor activity has been proposed to be due to the oxidation of 4-OHA by tyrosinase to cytotoxic oxidation products. Dose-dependent cytotoxicity was observed when cells were cultured for 72 h in the presence of 4-OHA. At 100 microM, 4-OHA produced growth inhibition of 62%, 32%, and 55% in melanoma, hepatoma, and kidney cell lines, respectively. No effect was seen at 10 microM 4-OHA. 1,000 microM 4-OHA produced 100% kill. Tyrosinase activity was detected only in melanoma cells. The effect of 100 microM 4-OHA on the incorporation of 3H DNA precursors in melanoma, hepatoma, and kidney cells was also studied. Thymidine incorporation was inhibited in all three cell lines at the lowest cell density tested, with the greatest inhibition seen on melanoma cells. As cell density increased, the effect of 4-OHA on thymidine incorporation decreased. With respect to RNA synthesis, 4-OHA significantly reduced the incorporation of uridine in all three cell lines, with the greatest effect in melanoma cells. Cell density also affected the inhibition of uridine incorporation, but to a lesser extent than that observed on thymidine incorporation. The effect of 4-OHA on leucine incorporation was modest and uninfluenced by cell density. Thus, cytotoxicity of 4-OHA may involve two different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2497444

Kulkarni, G A; Nathanson, L

1989-01-01

212

Parafibromin inhibits cancer cell growth and causes G1 phase arrest  

SciTech Connect

The HRPT2 (hereditary hyperparathyroidism type 2) tumor suppressor gene encodes a ubiquitously expressed 531 amino acid protein termed parafibromin. Inactivation of parafibromin predisposes one to the development of HPT-JT syndrome. To date, the role of parafibromin in tumorigenesis is largely unknown. Here, we report that parafibromin is a nuclear protein that possesses anti-proliferative properties. We show that overexpression of parafibromin inhibits colony formation and cellular proliferation, and induces cell cycle arrest in the G1 phase. Moreover, HPT-JT syndrome-derived mutations in HRPT2 behave in a dominant-negative manner by abolishing the ability of parafibromin to suppress cell proliferation. These findings suggest that parafibromin has a critical role in cell growth, and mutations in HRPT2 can directly inhibit this role.

Zhang Chun [Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Kong Dong [Laboratory of Mammalian Developmental Genetics, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Tan, M.-H. [Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Department of Medical Oncology, National Cancer Center (Singapore); Pappas, Donald L. [Laboratory of Chromosome Replication, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Wang, P.-F. [Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Chen, Jindong [Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Farber, Leslie [Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Zhang Nian [Laboratory of Mammalian Developmental Genetics, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Koo, H.-M. [Laboratory of Cancer Pharmacogenetics, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Weinreich, Michael [Laboratory of Chromosome Replication, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Williams, Bart O. [Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Teh, B.T. [Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503 (United States)]. E-mail: bin.teh@vai.org

2006-11-10

213

Effect of organic acids on the growth and lipid accumulation of oleaginous yeast Trichosporon fermentans  

PubMed Central

Background Microbial lipids have drawn increasing attention in recent years as promising raw materials for biodiesel production, and the use of lignocellulosic hydrolysates as carbon sources seems to be a feasible strategy for cost-effective lipid fermentation with oleaginous microorganisms on a large scale. During the hydrolysis of lignocellulosic materials with dilute acid, however, various kinds of inhibitors, especially large amounts of organic acids, will be produced, which substantially decrease the fermentability of lignocellulosic hydrolysates. To overcome the inhibitory effects of organic acids, it is critical to understand their impact on the growth and lipid accumulation of oleaginous microorganisms. Results In our present work, we investigated for the first time the effect of ten representative organic acids in lignocellulosic hydrolysates on the growth and lipid accumulation of oleaginous yeast Trichosporon fermentans cells. In contrast to previous reports, we found that the toxicity of the organic acids to the cells was not directly related to their hydrophobicity. It is worth noting that most organic acids tested were less toxic than aldehydes to the cells, and some could even stimulate the growth and lipid accumulation at a low concentration. Unlike aldehydes, most binary combinations of organic acids exerted no synergistic inhibitory effects on lipid production. The presence of organic acids decelerated the consumption of glucose, whereas it influenced the utilization of xylose in a different and complicated way. In addition, all the organic acids tested, except furoic acid, inhibited the malic activity of T. fermentans. Furthermore, the inhibition of organic acids on cell growth was dependent more on inoculum size, temperature and initial pH than on lipid content. Conclusions This work provides some meaningful information about the effect of organic acid in lignocellulosic hydrolysates on the lipid production of oleaginous yeast, which is helpful for optimization of biomass hydrolysis processes, detoxified pretreatment of hydrolysates and lipid production using lignocellulosic materials. PMID:22260291

2012-01-01

214

Possible intermolecular interaction between quinolones and biphenylacetic acid inhibits gamma-aminobutyric acid receptor sites.  

PubMed Central

The combination of some new quinolone antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen, is known to specifically induce functional blockade of the gamma-aminobutyric acid (GABA) receptors. The mechanisms of these drug interactions were further examined. Scatchard analysis of [3H]muscimol binding to rat brain plasma membranes in the presence of enoxacin and BPAA revealed that a significant decrease in the number of muscimol binding sites was produced without affecting the affinity of binding to the receptors. In the presence of norfloxacin, BPAA inhibited muscimol binding the most potently of the six BPAA-related compounds tested. Fenbufen and 9,10-dihydro-gamma-oxo-2-phenanthrenebutyric acid also inhibited the binding, and 4-biphenylcarboxylic acid and methyl 4-biphenylacetate inhibited it slightly, but 3-benzoylpropionic acid exhibited no competitive inhibition. Accordingly, hybrid molecules of norfloxacin and BPAA were synthesized for stereochemical analysis of these drug interactions. A hybrid with a -CONH(CH2)3- chain between norfloxacin and BPAA (flexible structure) inhibited muscimol binding, and intracisternal injection of this hybrid caused clonic convulsions in mice more potently than the combination of norfloxacin and BPAA did. In contrast, a hybrid linked by -CONH- (stretched structure) showed almost no such inhibitory effect. 1H NMR analysis indicated the presence of intramolecular attraction at the quinoline ring of the hybrid exhibiting the antagonistic activity. These results suggest the possibility that quinolones and BPAA interact with the GABA receptor at nearby sites and that the binding affinity of quinolones to the GABA receptors is largely enhanced by the intermolecular interaction with BPAA. PMID:7840564

Akahane, K; Kimura, Y; Tsutomi, Y; Hayakawa, I

1994-01-01

215

Effects of elaidic Acid, a predominant industrial trans Fatty Acid, on bacterial growth and cell surface hydrophobicity of lactobacilli.  

PubMed

The consumption of trans fatty acids (TFAs) increases the risk of cardiovascular diseases and coronary heart disease in human, and there are no effective ways to remove TFAs after consumption. The aim of this study was to investigate the effects of elaidic acid on bacterial growth, cell surface hydrophobicity of lactobacilli, and metabolism of elaidic acid by lactobacilli. Lactobacilli were inoculated in MRS broth containing 0, 100, 200, and 500 mg/L of elaidic acid. Viable cell counts of lactobacilli were enumerated, concentrations of elaidic acid were determined, and cell surface hydrophobicity of lactobacilli was measured. The results showed that the growth of lactobacilli was significantly inhibited by 500 mg/L of elaidic acid, however, a cell count of 8.50 log10 CFU/mL was still reached for tested lactobacilli after 24-h incubation. In particular, a reduction of elaidic acid was found for tested lactobacilli after 24-h incubation as compared to its initial concentration of 200 mg/L. However, cell surface hydrophobicity showed no correlations with the metabolism of elaidic acid by lactobacilli. Moreover, elaidic acid was able to influence cell surface hydrophobicity, and the decrease in hydrophobicity was more obvious in Lactobacillus paracasei and Lactobacillus casei compared with that in other tested lactobacilli. This study suggests that elaidic acid could change physiochemical surface properties of lactobacilli and the lactobacilli have the potential to reduce TFAs. PMID:25384717

Wu, Qinglong; Shah, Nagendra P

2014-12-01

216

Somatostatin inhibits colon cancer cell growth through cyclooxygenase-2 downregulation  

PubMed Central

Background and purpose: Cyclooxygenase-2 (COX-2) is expressed in colonic neoplasms, where it supports cell proliferation via prostaglandin E2 (PGE2) production. This study investigated the effects of somatostatin-14 on COX-2 expression, PGE2 production and proliferation in colon cancer cells. Experimental approach: Human colon adenocarcinoma cell lines Caco-2, HT-29 and HCT116 were used. The following techniques were employed: colourimetric assay for cell growth; 5-bromo-2?-deoxyuridine assay for DNA synthesis; enzyme immunoassay for PGE2; COX-2 mRNA silencing; RT–PCR or Western blot for somatostatin receptor subtypes, cyclooxygenase isoforms, phosphorylated-ERK-1/ERK-2 and phosphorylated-Akt. Key results: HT-29 and Caco-2 cells expressed COX-2 and somatostatin receptors (sst3/4/5 and sst3/5, respectively). HCT116 cells did express somatostatin receptors (sst2/3/5), but not COX-2. Somatostatin-14 inhibited basal COX-2 expression, PGE2 production, DNA synthesis and growth in Caco-2 cells and these effects were prevented by BN81658 (sst3 receptor antagonist). Basal proliferation of HT-29, HCT116 and COX-2-silenced Caco-2 cells was not affected by somatostatin-14. Stimulation of HT-29 cells with gastrin-17 elicited increments of ERK-1/ERK-2 and Akt phosphorylation, COX-2 expression, PGE2 production, DNA synthesis and cell growth, which were all counteracted by somatostatin-14. Somatostatin-14-induced inhibition of COX-2 expression, PGE2 production and DNA synthesis were blocked by BIM23056 (sst5 receptor antagonist). Conclusions and implications: Somatostatin decreases COX-2 expression and function in colon cancer cells via activation of sst3 or sst5 receptors, and these effects contribute to the inhibitory action of somatostatin on cell proliferation. These findings can be relevant to the development of therapeutic strategies based on the modulation of the COX-2 pathway. PMID:18587421

Colucci, R; Blandizzi, C; Ghisu, N; Florio, T; Del Tacca, M

2008-01-01

217

Inhibition of Breast Cancer Cell Growth in Vitro by a Tyrosine Kinase Inhibitor1  

Microsoft Academic Search

Human breast cancer cell proliferation is regulated by growth factors that bind to receptors with intrinsic tyrosine kinase (TK) activity, includ ing the epidermal growth factor (EGF) receptor. To determine whether inhibition of receptor TK activity inhibits tumor growth, we studied the effects of a tyrosine kinase inhibitor, RG-13022, on cultured human breast cancer cells. RG-13022 represents a class of

Kaladhar B. Reddy; Gina L. Mangold; Atul K. Tandon; Toshiyuki Yoneda; Gregory R. Mundy; Asher Zilberstein; C. Kent Osborne

1992-01-01

218

Autocrine growth inhibition by transforming growth factor ?-1 (TGF?-1) in human neuroendocrine tumour cells  

PubMed Central

Background and aim: The role of transforming growth factor ?-1 (TGF?-1) in neuroendocrine tumour biology is currently unknown. We therefore examined the expression and biological significance of TGF? signalling components in neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) tract. Methods: Expression of TGF?-1 and its receptors, Smads and Smad regulated proteins, was examined in surgically resected NET specimens and human NET cell lines by immunohistochemistry, reverse transcriptase-polymerase chain reaction, immunoblotting, and ELISA. Activation of TGF?-1 dependent promoters was tested by transactivation assays. Growth regulation was evaluated by cell numbers, soft agar assays, and cell cycle analysis using flow cytometry. The role of endogenous TGF? was assessed by a TGF? neutralising antibody and stable transfection of a dominant negative TGF?R II receptor construct. Results: Coexpression of TGF?-1 and its receptors TGF?R I and TGF?R II was detected in 67% of human NETs and in all three NET cell lines examined. NET cell lines expressed the TGF? signal transducers Smad 2, 3, and 4. In two of the three cell lines, TGF?-1 treatment resulted in transactivation of a TGF? responsive reporter construct as well as inhibition of c-myc and induction of p21(WAF1) expression. TGF?-1 inhibited anchorage dependent and independent growth in a time and dose dependent manner in TGF?-1 responsive cell lines. TGF?-1 mediated growth inhibition was due to G1 arrest without evidence of induction of apoptosis. Functional inactivation of endogenous TGF? revealed the existence of an autocrine antiproliferative loop in NET cells. Conclusions: Neuroendocrine tumour cells of the gastroenteropancreatic tract are subject to paracrine and autocrine growth inhibition by TGF?-1, which may account in part for the low proliferative index of this tumour entity. PMID:12912863

Wimmel, A; Wiedenmann, B; Rosewicz, S

2003-01-01

219

Proteolytic Pathways Induced by Herbicides That Inhibit Amino Acid Biosynthesis  

PubMed Central

Background The herbicides glyphosate (Gly) and imazamox (Imx) inhibit the biosynthesis of aromatic and branched-chain amino acids, respectively. Although these herbicides inhibit different pathways, they have been reported to show several common physiological effects in their modes of action, such as increasing free amino acid contents and decreasing soluble protein contents. To investigate proteolytic activities upon treatment with Gly and Imx, pea plants grown in hydroponic culture were treated with Imx or Gly, and the proteolytic profile of the roots was evaluated through fluorogenic kinetic assays and activity-based protein profiling. Results Several common changes in proteolytic activity were detected following Gly and Imx treatment. Both herbicides induced the ubiquitin-26 S proteasome system and papain-like cysteine proteases. In contrast, the activities of vacuolar processing enzymes, cysteine proteases and metacaspase 9 were reduced following treatment with both herbicides. Moreover, the activities of several putative serine protease were similarly increased or decreased following treatment with both herbicides. In contrast, an increase in YVADase activity was observed under Imx treatment versus a decrease under Gly treatment. Conclusion These results suggest that several proteolytic pathways are responsible for protein degradation upon herbicide treatment, although the specific role of each proteolytic activity remains to be determined. PMID:24040092

Zulet, Amaia; Gil-Monreal, Miriam; Villamor, Joji Grace; Zabalza, Ana; van der Hoorn, Renier A. L.; Royuela, Mercedes

2013-01-01

220

Methoxyacetic acid suppresses prostate cancer cell growth by inducing growth arrest and apoptosis  

PubMed Central

Methoxyacetic acid (MAA) is a primary metabolite of ester phthalates that are used in production of consumer products and pharmaceutical products. MAA causes embryo malformation and spermatocyte death through inhibition of histone deacetylases (HDACs). Little is known about MAA’s effects on cancer cells. In this study, two immortalized human normal prostatic epithelial cell lines (RWPE-1 and pRNS-1-1) and four human prostate cancer cell lines (LNCaP, C4-2B, PC-3, and DU-145) were treated with MAA at different doses and for different time periods. Cell viability, apoptosis, and cell cycle analysis were performed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR, Western blot, and chromatin immunoprecipitation analyses. We found that MAA dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. MAA-induced apoptosis was due to down-regulation of the anti-apoptotic gene baculoviral inhibitor of apoptosis protein repeat containing 2 (BIRC2, also named cIAP1), leading to activation of caspases 7 and 3 and turning on the downstream apoptotic events. MAA-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and CDK2 expression at the late time. MAA up-regulated p21 expression through inhibition of HDAC activities, independently of p53/p63/p73. These findings demonstrate that MAA suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which suggests that MAA could be used as a potential therapeutic drug for prostate cancer. PMID:25606576

Parajuli, Keshab R; Zhang, Qiuyang; Liu, Sen; Patel, Neil K; Lu, Hua; Zeng, Shelya X; Wang, Guangdi; Zhang, Changde; You, Zongbing

2014-01-01

221

Release of an acid phosphatase activity during lily pollen tube growth involves components of the secretory pathway  

Microsoft Academic Search

Summary.   An acid phosphatase (acPAse) activity was released during germination and tube growth of pollen of Lilium longiflorum Thunb. By inhibiting components of the secretory pathway, the export of the acPase activity was affected and tube growth\\u000a stopped. Brefeldin A (1??M) and cytochalasin D (1??M), which block the production and transport of secretory vesicles, respectively,\\u000a inhibited the acPase secretion. The

Hala Ibrahim; Heidi Pertl; Klaus Pittertschatscher; Ezzat Fadl-Allah; Ahmed El-Shahed; Friedrich-Wilhelm Bentrup; Gerhard Obermeyer

2002-01-01

222

Synthesis and cholinesterase inhibition of cativic acid derivatives.  

PubMed

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

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

2014-08-01

223

Inhibition of Klebsiella pneumoniae Growth and Capsular Polysaccharide Biosynthesis by Fructus mume.  

PubMed

Klebsiella pneumoniae is the predominant pathogen isolated from liver abscess of diabetic patients in Asian countries. With the spread of multiple-drug-resistant K. pneumoniae, there is an increasing need for the development of alternative bactericides and approaches to block the production of bacterial virulence factors. Capsular polysaccharide (CPS), especially from the K1 and K2 serotypes, is considered the major determinant for K. pneumoniae virulence. We found that extracts of the traditional Chinese medicine Fructus mume inhibited the growth of K. pneumoniae strains of both serotypes. Furthermore, Fructus mume decreased the mucoviscosity, and the CPS produced in a dose-dependent manner, thus reducing bacterial resistance to serum killing. Quantitative reverse transcription polymerase chain reaction analyses showed that Fructus mume downregulated the mRNA levels of cps biosynthesis genes in both serotypes, possibly by increasing the intracellular iron concentration in K. pneumoniae. Moreover, citric acid, a major organic acid in Fructus mume extracts, was found to have an inhibitory effect on growth and CPS biosynthesis in K. pneumoniae. Taken together, our results indicate that Fructus mume not only possesses antibacterial activity against highly virulent K. pneumoniae strains but also inhibits bacterial CPS biosynthesis, thereby facilitating pathogen clearance by the host immune system. PMID:24062785

Lin, Tien-Huang; Huang, Su-Hua; Wu, Chien-Chen; Liu, Hsin-Ho; Jinn, Tzyy-Rong; Chen, Yeh; Lin, Ching-Ting

2013-01-01

224

Selective growth-inhibiting effects of compounds identified in Tabebuia impetiginosa inner bark on human intestinal bacteria.  

PubMed

The growth-inhibiting activity of anthraquinone-2-carboxylic acid and lapachol identified in the inner bark of taheebo, Tabebuia impetiginosa, toward 10 human intestinal bacteria was evaluated by using a paper disk diffusion bioassay and compared to those of seven lapachol congeners (1,4-naphthoquinone, naphthazarin, menadione, lawsone, plumbagin, juglone, and dichlone) as well as two commercially available antibiotics, chloramphenicol and tetracycline. Anthraquinone-2-carboxylic acid exhibited very strong growth inhibition of Clostridium paraputrificum at 1 microg/disk while 100 microg/disk of lapachol was needed for moderate growth inhibition of the same organism. These two isolates exhibited weak inhibition of Clostridium perfringens and Escherichia coli at 100 microg/disk while no adverse effects were observed on the growth of Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus acidophilus, and Lactobacillus casei at 1000 microg/disk. Structure-activity relationships indicate that a methyl group in the C-2 position of 1,4-naphthoquinone derivatives might play an important role in antibacterial activity. PMID:15713033

Park, Byeoung-Soo; Kim, Jun-Ran; Lee, Sung-Eun; Kim, Kyoung Soon; Takeoka, Gary R; Ahn, Young-Joon; Kim, Jeong-Han

2005-02-23

225

[Inhibition of IAA-induced growth of wheat coleoptile fragments by chitin-chitosan oligomers].  

PubMed

We studied the comparative effects of the phytohormone indolylacetic acid (IAA) and chitooligosaccharides (5-10 kDa, degree of deacetylation 35%) on the growth of coleoptile fragments of 3-day wheat germlings. IAA (10 mg/l) stimulated elongation of coleoptile fragments by 80%, as compared to the control (water). Chitooligosaccharides at 0.01-1500 mg/l or higher did not exert auxin-like effects, but at 100 mg/l or higher, suppressed elongation of the coleoptile fragments, as compared to the control (water). Incubation of coleoptile fragments in solutions containing both IAA and chitooligosaccharides (100 mg/l or higher) suppressed their IAA-induced elongation, which correlated with the inhibition of growth of 3-day wheat germlings after wetting seeds in solutions of chitooligosaccharides. It has been proposed that the phytohormone-like properties of chitooligosaccharides can be related to changes in the endogenous balance of phytohormones in plants. PMID:11963543

Kha?rullin, R M; Akhmetova, I E; Iusupova, Z R

2002-01-01

226

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

Microsoft Academic Search

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

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

1993-01-01

227

Vascular endothelial growth factor a inhibition in gastric cancer.  

PubMed

Angiogenesis is a vital process in the progression and metastasis of solids tumors including gastric adenocarcinoma. Tumors induce angiogenesis by secreting proangiogenic molecules such as vascular endothelial growth factor A (VEGF-A), and VEGF-A inhibition has become a common therapeutic strategy for many cancers. Several drugs targeting the VEGF-A pathway have been approved for clinical use in selected solid tumors, and several anti-VEGF-A strategies have been examined for gastric cancer. Phase II studies suggested that bevacizumab, an anti-VEGF antibody, can increase the efficacy of chemotherapy for advanced gastric cancer, but two international phase III trials failed to show an overall survival benefit. Two more recent international phase III trials have examined ramucirumab, an antibody targeting the primary receptor for VEGF-A, as second-line therapy for advanced gastric cancer and found a survival benefit both as single agent therapy and when combined with chemotherapy. Finally, correlative science studies suggest that the VEGF-A pathway may have varying importance in gastric cancer progression depending on ethnicity or race. This article will review the preclinical and clinical studies on the role of the VEGF-A pathway inhibition in gastric cancer. PMID:24993497

Park, Do Joong; Thomas, Nicholas J; Yoon, Changhwan; Yoon, Sam S

2015-01-01

228

Kinetics of octacalcium phosphate crystal growth in the presence of organic acids  

NASA Astrophysics Data System (ADS)

Octacalcium phosphate (OCP) is an important P solid phase in geochemical and biological systems and has been recognized as a precursor phase to the formation of thermodynamically more stable hydroxyapatite (HAP). Metastability of OCP with respect to HAP may be explained by precipitation kinetics and the influence of dissolved organic C (DOC) on crystal growth. Octacalcium phosphate precipitation was measured at pH 6.0 and 25°C in the absence and presence of organic acids commonly found in natural waters and soil solutions using a seeded crystal growth constant composition method. Rate constants for OCP precipitation were calculated from the following expression: Rate = kS(IAP 1/8 - K sp1/8) n, where k is the rate constant (L 7 mol -6 m -2 s -1), S is OCP seed crystal surface area (m 2 L -1), IAP = ion activity product, Ksp = OCP solubility constant (mol 8 L -8), and n is the rate reaction order. The rate constant for OCP precipitation in the absence of organic acids was 10 34.93·L 7 mol -6 m -2 s -1. Humic, fulvic, tannic, and citric acids were added to OCP crystal growth experiments at total soluble (C TS) C levels ranging from 20 ?M to 2 mM. Inhibition of OCP precipitation was nearly complete (99% ) in the presence of 1.0 mM C TS as humic acid. At the same level of C TS, OCP precipitation was inhibited by 97,88, and 68% in the presence of fulvic, citric, and tannic acids, respectively. Inhibition of precipitation is caused by adsorption of organic acids onto OCP surfaces blocking active crystal growth sites. The ability of organic acids to inhibit OCP crystal growth is related to their hydrophobicity, functional group content, size, geometry, and orientation on the crystal surface. Precipitation kinetics and crystal growth inhibition by organic acids may explain the metastability of dicalcium phosphate dihydrate (DCPD) and OCP with respect to thermodynamically more stable HAP often observed in geochemical environments.

Grossl, Paul R.; Inskeep, William P.

1992-05-01

229

Inhibition of activity of the ethylene-forming enzyme by ?( p -chlorophenoxy)isobutyric acid  

Microsoft Academic Search

?(p-Chlorophenoxy)isobutyric acid (PCIB) inhibited indole-3-acetic acid (IAA)-induced ethylene production in etiolated mung bean hypocotyl sections. The endogenous level of 1-aminocyclopropane-1-carboxylic acid (ACC) was not significantly affected by PCIB, indicating that PCIB exerted its effect primarily by inhibiting the activity of the ethylene-forming enzyme (EFE). This conclusion was supported by the observations that PCIB inhibited the conversion of exogenously applied ACC

Tova Trebitsh; Joseph Riov

1987-01-01

230

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 ...

231

Inhibition of rat colon tumor isograft growth with dequalinium chloride.  

PubMed

In searching for a new approach to the systemic treatment of colorectal carcinoma, we have observed that certain lipophilic cationic compounds are accumulated and retained for a significantly longer period in the mitochondria of living carcinoma cells than in normal cells or sarcoma cells. We report the in vivo therapeutic effect of one of these compounds, dequalinium chloride, on the W163 rat colon carcinoma isograft, which grows rapidly in Wistar/Furth rats after primary tumor implantation, and which recurs rapidly after primary tumor resection. In the primary transplant model, tumors were implanted, and daily dequalinium chloride treatments were begun the following day in doses ranging from 1 to 10 mg/kg. In the recurrence model, isografts were implanted, allowed to grow for one week, and then all gross tumor was resected. Dequalinium chloride was administered in varying daily doses starting the day after resection. In both models, tumor was removed on day 11 after implantation or resection. At sublethal doses, dequalinium chloride significantly inhibited primary tumor growth to 60% that of controls and recurrent tumor growth to 50% that of controls. We propose that this unique biologic approach of targeting carcinoma mitochondria with lipophilic cationic compounds may provide a major new opportunity for treating colorectal carcinoma. PMID:3778199

Bleday, R; Weiss, M J; Salem, R R; Wilson, R E; Chen, L B; Steele, G

1986-11-01

232

Control of growth by picolinic acid: Differential response of normal and transformed cells  

PubMed Central

Picolinic acid reversibly inhibits the growth of cultured cells. Fourteen other pyridine derivatives were ineffective or toxic. Untransformed normal rat kidney (NRK) cells are reversibly arrested in the G1 stage of the growth cycle as shown by cell counts, mitotic index, [3H]thymidine incorporation, and flow microfluorometry. Flow microfluorometry was used to monitor the effects of picolinic acid on numerous other cell lines. Normal cells are blocked in G1, whereas transformed cells show responses that are dependent upon the transforming virus and independent of species or origin of the cell line. Kirsten sarcoma virus-transformed cells are blocked in G1. Simian virus 40-transformed cells progress to a G2 block. Cells transformed by polyoma or Harvey sarcoma virus with Moloney virus coat have flow microfluorometry profiles that indicate blocks in both G1 and G2. Cells transformed with Moloney sarcoma virus are not blocked in a specific phase of the cell cycle. Picolinic acid does not change the levels of NAD+ plus NADH; however, the growth inhibition by picolinic acid is partially overcome by nicotinamide. These results suggest that picolinic acid interacts with a specific growth control mechanism that may involve NAD+ and that this control mechanism is altered by different transforming viruses in different manners. Images PMID:197524

Fernandez-Pol, J. A.; Bono, Vincent H.; Johnson, George S.

1977-01-01

233

Promotion of plant growth by polymers of lactic acid  

Microsoft Academic Search

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

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

1990-01-01

234

Lunularic acid, a common endogenous growth inhibitor of liverworts.  

PubMed

By gas-liquid chromotography and thin layer chromatography, an endogenous growth inhibitor of Lunularia cruciata has been detected in seven other representatives of the class of liverworts. All liverworts so far examined have been found to contain lunularic acid. Evidence for the identity of the previously isolated, but unidentified, endogenous growth inhibitor of Marchantia polymorpha and lunularic acid is presented. PMID:24493279

Pryce, R J

1971-12-01

235

Lunularic acid, a common endogenous growth inhibitor of liverworts  

Microsoft Academic Search

By gas-liquid chromotography and thin layer chromatography, an endogenous growth inhibitor of Lunularia cruciata has been detected in seven other representatives of the class of liverworts. All liverworts so far examined have been found to contain lunularic acid. Evidence for the identity of the previously isolated, but unidentified, endogenous growth inhibitor of Marchantia polymorpha and lunularic acid is presented.

R. J. Pryce

1971-01-01

236

Growth of Streptomyces Hygroscopicus in Rotating-Wall Bioreactor Under Simulated Microgravity Inhibits Rapamycin Production  

NASA Technical Reports Server (NTRS)

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.

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

2000-01-01

237

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

NASA Technical Reports Server (NTRS)

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.

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

2000-01-01

238

Ursolic Acid Inhibits Proliferation and Induces Apoptosis of Cancer Cells In Vitro and In Vivo  

PubMed Central

The aims of the study are to explore the effect of ursolic acid (UA) on the growth of gastric cancer cell line BGC-803 and hepatocellular cancer cell H22 xenograft and to understand the mechanism. UA inhibits growth of BGC-803 cells in vitro in dose-dependent and time-dependent manner. Treated with UA in vivo, tumor cells can be arrested to G0/G1 stage. The apoptotic rate was significantly increased in tumor cells treated with UA both in vitro and in vivo. DNA fragmentation was found in BGC-803 cells exposed to UA. UA activated caspase-3, -8, and -9 and down regulated expression of Bcl-2 in BGC-803 cells. The expression of caspase-3 and -8 was elevated in tumor cells from xenograft treated with UA. 18F-FLT PET-CT imaging confirmed tumor model and UA effectiveness. Our results indicated that UA inhibits growth of tumor cells both in vitro and in vivo by decreasing proliferation of cells and inducing apoptosis. PMID:21716649

Wang, Xuemei; Zhang, Fan; Yang, Ling; Mei, Ying; Long, Hai; Zhang, Xiaowen; Zhang, Jialing; Qimuge-Suyila; Su, Xiulan

2011-01-01

239

Caffeic Acid Phenethyl Ester Inhibits Epithelial-Mesenchymal Transition of Human Pancreatic Cancer Cells  

PubMed Central

Background. This study aimed to investigate the effect of propolis component caffeic acid phenethyl ester (CAPE) on epithelial-mesenchymal transition (EMT) of human pancreatic cancer cells and the molecular mechanisms underlying these effects. Methods. The transforming growth factor ? (TGF-?-) induced EMT in human pancreatic PANC-1 cancer cells was characterized by observation of morphology and the expression of E-cadherin and vimentin by western blotting. The migration potential was estimated with wound closure assay. The expression of transcriptional factors was measured by quantitative RT-PCR and immunocytochemistry staining. The orthotopic pancreatic cancer xenograft model was used for in vivo assessment. Results. The overexpression of vimentin was attenuated by CAPE, and the alteration in morphology from polygonal to spindle shape was partially reversed by CAPE. Furthermore, CAPE delayed the TGF-?-stimulated migration potential. CAPE treatment did not reduce the expression levels of Smad 2/3, Snail 1, and Zeb 1 but inhibited the expression of transcriptional factor Twist 2. By using an orthotopic pancreatic cancer model, CAPE suppressed the expression of Twist 2 and growth of PANC-1 xenografts without significant toxicity. Conclusion. CAPE could inhibit the orthotopic growth and EMT of pancreatic cancer PANC-1 cells accompanied by downregulation of vimentin and Twist 2 expression. PMID:23662124

Chen, Ming-Jen; Shih, Shou-Chuan; Wang, Horng-Yuan; Lin, Ching-Chung; Liu, Chia-Yuan; Wang, Tsang-En; Chu, Cheng-Hsin; Chen, Yu-Jen

2013-01-01

240

Combination MET inhibition and Topoisomerase I inhibition block cell growth of Small Cell Lung Cancer  

PubMed Central

Small cell lung cancer (SCLC) is a devastating disease, and current therapies have not greatly improved the 5-year survival rates. Topoisomerase (Top) inhibition is a treatment modality for SCLC; however, the response is short lived. Consequently, our research has focused on improving SCLC therapeutics through the identification of novel targets. Previously, we identified MNNG HOS transforming gene (MET) to be overexpressed and functional in SCLC. Herein, we investigated the therapeutic potential of combinatorial targeting of MET using SU11274 and Top1 using 7-ethyl-10-hydroxycamptothecin (SN-38). MET and TOP1 gene copy numbers and protein expression were determined in 29 patients with limited (n = 11) and extensive (n = 18) disease. MET gene copy number was significantly increased (>6 copies) in extensive disease compared with limited disease (P = 0.015). Similar TOP1 gene copy numbers were detected in limited and extensive disease. Immunohistochemical staining revealed a significantly higher Top1 nuclear expression in extensive (0.93) versus limited (0.15) disease (P = 0.04). Interestingly, a significant positive correlation was detected between MET gene copy number and Top1 nuclear expression (r = 0.5). In vitro stimulation of H82 cells revealed hepatocyte growth factor (HGF)–induced nuclear colocalization of p-MET and Top1. Furthermore, activation of the HGF/MET axis enhanced Top1 activity, which was abrogated by SU11274. Combination of SN-38 with SU11274 dramatically decreased SCLC growth as compared with either drug alone. Collectively, these findings suggest that the combinatorial inhibition of MET and Top1 is a potentially efficacious treatment strategy for SCLC. PMID:24327519

Rolle, Cleo E.; Kanteti, Rajani; Surati, Mosmi; Nandi, Suvobroto; Dhanasingh, Immanuel; Yala, Soheil; Tretiakova, Maria; Arif, Qudsia; Hembrough, Todd; Brand, Toni M.; Wheeler, Deric L.; Husain, Aliya N.; Vokes, Everett E.; Bharti, Ajit; Salgia, Ravi

2014-01-01

241

Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation  

SciTech Connect

Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE{sub 2} production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-?B signaling showed that LAME inhibits the phosphorylation of I?B? and I?B?, preventing their degradation and the nuclear translocation of the NF-?B p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-? (TGF-?)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-? and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-?). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ? LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. ? IL-6, TNF-? and IP-10 were also inhibited by LAME. ? Inhibition of TAK-1 activation is the mechanism involved in this process. ? LAME improved survival in a mouse model of endotoxemia. ? LAME reduced the circulatory levels of cytokines (IL-6, TNF-?).

Cuadrado, Irene [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain)] [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Cidre, Florencia; Herranz, Sandra [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain)] [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain); Estevez-Braun, Ana [Instituto Universitario de Bio-Orgánica “Antonio González”. Universidad de La Laguna. Avda. Astrofísico Fco. Sánchez 2. 38206. La Laguna, Tenerife (Spain) [Instituto Universitario de Bio-Orgánica “Antonio González”. Universidad de La Laguna. Avda. Astrofísico Fco. Sánchez 2. 38206. La Laguna, Tenerife (Spain); Instituto Canario de Investigaciones del Cáncer (ICIC) (Spain); Heras, Beatriz de las, E-mail: lasheras@farm.ucm.es [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Hortelano, Sonsoles, E-mail: shortelano@isciii.es [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain)] [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain)

2012-01-01

242

Species-specific Inhibition of Porphobilinogen Synthase by 4-Oxosebacic Acid*  

E-print Network

-Oxosebacic acid (4-OSA) and 4,7-dioxosebacic acid (4,7-DOSA) are bisubstrate reaction intermediate ana- logs). Here we have characterized a very differ- ent species selectivity for 4-OSA inhibition of PBGS and pro

243

Role of Volatile Fatty Acids in Development of the Cecal Microflora in Broiler Chickens during Growth  

PubMed Central

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 members of the Enterobacteriaceae and enterococci are present in large numbers in 3-day-old broilers and start to decrease when broilers grow older. Lactobacilli are present in large numbers as well in 3-day-old broilers, but they remain stable during the growth of broilers. Acetate, butyrate, and propionate increase from undetectable levels in 1-day-old broilers to high concentrations in 15-day-old broilers, after which they stabilize. Significant negative correlations could be calculated between numbers of Enterobacteriaceae and concentrations of undissociated acetate, propionate, and butyrate. Furthermore, pure cultures of Enterobacteriaceae isolated from the ceca were grown in the presence of volatile fatty acids. Growth rates and maximal optical density decreased when these strains grew in the presence of increasing volatile fatty acid concentrations. It is concluded that volatile fatty acids are responsible for the reduction in numbers of Enterobacteriaceae in the ceca of broiler chickens during growth. PMID:10831435

van der Wielen, Paul W. J. J.; Biesterveld, Steef; Notermans, Servé; Hofstra, Harm; Urlings, Bert A. P.; van Knapen, Frans

2000-01-01

244

Role of volatile fatty acids in development of the cecal microflora in broiler chickens during growth.  

PubMed

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 members of the Enterobacteriaceae and enterococci are present in large numbers in 3-day-old broilers and start to decrease when broilers grow older. Lactobacilli are present in large numbers as well in 3-day-old broilers, but they remain stable during the growth of broilers. Acetate, butyrate, and propionate increase from undetectable levels in 1-day-old broilers to high concentrations in 15-day-old broilers, after which they stabilize. Significant negative correlations could be calculated between numbers of Enterobacteriaceae and concentrations of undissociated acetate, propionate, and butyrate. Furthermore, pure cultures of Enterobacteriaceae isolated from the ceca were grown in the presence of volatile fatty acids. Growth rates and maximal optical density decreased when these strains grew in the presence of increasing volatile fatty acid concentrations. It is concluded that volatile fatty acids are responsible for the reduction in numbers of Enterobacteriaceae in the ceca of broiler chickens during growth. PMID:10831435

van Der Wielen, P W; Biesterveld, S; Notermans, S; Hofstra, H; Urlings, B A; van Knapen, F

2000-06-01

245

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

SciTech Connect

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.

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

246

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

PubMed Central

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

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

247

Caffeic acid inhibits in vitro rooting in mung bean [ Vigna radiata (L.) Wilczek] hypocotyls by inducing oxidative stress  

Microsoft Academic Search

Caffeic acid (CA), which is ubiquitously present in plants, is a potent phytotoxin affecting plant growth and physiology.\\u000a The aim of our study was to investigate whether CA-induced inhibition of adventitious root formation (ARF) in mung bean {Vigna radiata (L.) Wilczek [Phaseolus aureus Roxb.]} involves the induction of conventional stress responses. The effect of CA (0–1000 ?M) on ARF in mung

Harminder Pal Singh; Shalinder Kaur; Daizy R. Batish; Ravinder Kumar Kohli

2009-01-01

248

Endothelin inhibits cholangiocarcinoma growth by a decrease in the vascular endothelial growth factor expression  

PubMed Central

Background: Endothelins (ET-1, ET-2, ET-3) are peptides with vasoactive properties interacting with ETA and ETB receptors. ET-1 inhibits secretin-stimulated ductal secretion (hallmark of cholangiocyte growth) of cholestatic rats by interaction with ET receptors. Aim: The aims of the studies were to evaluate (i) the effect of ET-1 on cholangiocarcinoma growth in Mz-ChA-1 cells and nude mice and (ii) whether ET-1 regulation of cholangiocarcinoma growth is associated with changes in the expression of vascular endothelial growth factor-A (VEGF-A), VEGF-C, VEGF receptor-2 (VEGFR-2) and VEGFR-3. Methods: We determined the expression of ETA and ETB receptors on normal and malignant (Mz-ChA-1) cholangiocytes and human cholangiocarcinoma tissue and the effect of ET-1 on the proliferation and expression of VEGF-A, VEGF-C (regulators of tumour angiogenesis) and its receptors, VEGFR-2 and VEGFR-3, in Mz-ChA-1 cells. In vivo, Mz-ChA-1 cells were injected into the flanks of athymic mice and injections of ET-1 or saline into the tumours were performed daily. The effect of ET-1 on tumour size, cell proliferation, apoptosis, collagen quantity and the expression of VEGF-A and VEGF-C and VEGFR-2 and VEGFR-3 were measured after 73 days. Results: Higher expression of ETA and ETB was observed in malignant compared with normal cholangiocytes. ET-1 inhibited proliferation and VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression of Mz-ChA-1 cells. Chronic ET-1 treatment decreased tumour volume, tumour cell proliferation and VEGF-A and VEGF-C expression but increased apoptosis and collagen tissue deposition compared with controls. Conclusions: Modulation of VEGF-A and VEGF-C (by ET-1) may be important for managing cholangiocarcinoma growth. PMID:19291182

Fava, Giammarco; DeMorrow, Sharon; Gaudio, Eugenio; Franchitto, Antonio; Onori, Paolo; Carpino, Guido; Glaser, Shannon; Francis, Heather; Coufal, Monique; Marucci, Luca; Alvaro, Domenico; Marzioni, Marco; Horst, Trenton; Mancinelli, Romina; Benedetti, Antonio; Alpini, Gianfranco

2009-01-01

249

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

E-print Network

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

Levin, Judith G.

250

Crystal Growth and Molecular Modeling Studies of Inhibition of Struvite by Phosphocitrate  

Microsoft Academic Search

.   The inhibition by phosphocitrate of struvite crystal formation and growth has been examined in the present study. Crystal\\u000a growth in a gel matrix was controlled by phosphocitrate in a dose-dependent manner. The effects of inhibition were followed\\u000a using scanning electron microscopy, optical microscopy, and single crystal X-ray analysis. The presence of phosphocitrate\\u000a induced very strong, crystal face specific inhibition

A. Wierzbicki; J. D. Sallis; E. D. Stevens; M. Smith; C. S. Sikes

1997-01-01

251

Bile salts inhibit growth and induce apoptosis of human esophageal cancer cell line  

PubMed Central

AIM: To explore the effect of six bile salts, including glycoc-holate (GC), glycochenodeoxycholate (GCDC), glycodeoxy-cholate (GDC), taurocholate (TC), taurochenodeoxycholate (TCDC), taurodeoxycholate (TDC), and two bile acids including cholic acid (CA) and deoxycholic acid (DCA) on esophageal cancer Eca109 cell line. METHODS: Eca109 cells were exposed to six bile salts, two bile acids and the mixed bile salts at different concentrations for 24-72 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to detect the cell proliferation. Apoptotic morphology was observed by phase-contrast video microscopy and deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Sub-G1 DNA fragmentations and early apoptosis cells were assayed by flow cytometry (FCM) with propidium iodide (PI) staining and annexin V-FITC conjugated with PI staining. Apoptosis DNA ladders on agarose were observed. Activation of caspase-3 was assayed by FCM with FITC-conjugated monoclonal rabbit anti-active caspase-3 antibody and expressions of Bcl-2 and Bax proteins were examined immunocytochemically in 500 ?mol/L-TC-induced apoptosis cells. RESULTS: Five bile salts except for GC, and two bile acids and the mixed bile salts could initiate growth inhibition of Eca109 cells in a dose- and time-dependent manner. TUNEL, FCM, and DNA ladder assays all demonstrated apoptosis induced by bile salts and bile acids at 500 ?mol/L, except for GC. Early apoptosis cell percentages in Eca109 cells treated with GCDC, GDC, TC, TCDC, TDC, CA at 500 ?mol/L for 12 h, DCA at 500 ?mol/L for 6 h, and mixed bile salts at 1 000 ?mol/L for 12 h were 7.5%, 8.7%, 14.8%, 8.9%, 7.8%, 9.3%, 22.6% and 12.5%, respectively, all were significantly higher than that in control (1.9%). About 22% of the cell population treated with TC at 500 ?mol/L for 24 h had detectable active caspase-3, and were higher than that in the control (1%). Immunocytochemical assay suggested that TC down-regulated Bcl-2 protein level and up-regulated Bax protein level. CONCLUSION: GCDC, GDC, TC, TCDC, TDC, CA and DCA, except for GC, can inhibit growth and induce apoptosis of esophageal cancer Eca109 cells. Activation of caspase-3, decreased Bcl-2 protein and increased Bax protein are involved in TC-induced apoptosis of Eca109 cells. PMID:16127738

Zhang, Ru; Gong, Jun; Wang, Hui; Wang, Li

2005-01-01

252

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

Technology Transfer Automated Retrieval System (TEKTRAN)

The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB) is demonstrated to share biological activities with 4-formylaminooxyvinylglycine, a related molecule produced by Pseudomonas fluorescens WH6. We found that culture filtrates of a P. aeruginosa strain overproduc...

253

Aluminum stress inhibits root growth and alters physiological and metabolic responses in chickpea (Cicer arietinum L.).  

PubMed

Chickpea (Cicer arietinum L.) roots were treated with aluminum (Al(3+)) in calcium chloride (CaCl2) solution (pH 4.7) and growth responses along with physiological and metabolic changes were investigated. Al(3+) treatment for 7d resulted in a dose dependent decline of seed germination and inhibition of root growth. A significant (p ? 0.05) decline in fresh and dry biomass were observed after 7d of Al(3+) stress. The root growth (length) was inhibited after 24 and 48 h of stress imposition. The hydrogen peroxide (H2O2) levels increased significantly (p ? 0.05) with respect to control in Al(3+) treated roots. The hematoxylin and Evans blue assay indicated significant (p ? 0.05) accumulation of Al(3+) in the roots and loss of plasmamembrane integrity respectively. The time-course evaluation of lipid peroxidation showed increase in malondialdehyde (MDA) after 12, 24 and 48 h of stress imposition. Al(3+) treatment did not alter the MDA levels after 2 or 4 h of stress, however, a minor increase was observed after 6 and 10 h of treatment. The proton ((1)H) nuclear magnetic resonance (NMR) spectrum of the perchloric acid extracts showed variation in the abundance of metabolites and suggested a major metabolic shift in chickpea root during Al(3+) stress. The key differences that were observed include changes in energy metabolites. Accumulation of phenolic compounds suggested its possible role in Al(3+) exclusion in roots during stress. The results suggested that Al(3+) alters growth pattern in chickpea and induces reactive oxygen species (ROS) production that causes physiological and metabolic changes. PMID:25394801

Choudhury, Shuvasish; Sharma, Parul

2014-10-22

254

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

Microsoft Academic Search

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

Deborah J. Durnam; Russell L. Jones

1982-01-01

255

Failure of Amino Acid Homeostasis Causes Cell Death following Proteasome Inhibition  

PubMed Central

Summary The ubiquitin-proteasome system targets many cellular proteins for degradation and thereby controls most cellular processes. Although it is well established that proteasome inhibition is lethal, the underlying mechanism is unknown. Here, we show that proteasome inhibition results in a lethal amino acid shortage. In yeast, mammalian cells, and flies, the deleterious consequences of proteasome inhibition are rescued by amino acid supplementation. In all three systems, this rescuing effect occurs without noticeable changes in the levels of proteasome substrates. In mammalian cells, the amino acid scarcity resulting from proteasome inhibition is the signal that causes induction of both the integrated stress response and autophagy, in an unsuccessful attempt to replenish the pool of intracellular amino acids. These results reveal that cells can tolerate protein waste, but not the amino acid scarcity resulting from proteasome inhibition. PMID:22959274

Suraweera, Amila; Münch, Christian; Hanssum, Ariane; Bertolotti, Anne

2012-01-01

256

Fungitoxic effects of nonprotein imino acids on growth of saprophytic fungi isolated from the leaf surface of Calliandra haematocephala.  

PubMed Central

Four saprophytic and pathogenic fungi were isolated from the leaf surface of Calliandra haematocephala, a tropical legume known to contain large amounts of rare nonprotein imino acids in its leaves and seeds. The fungi Aspergillus niger, Aspergillus sp., Curvularia sp., and Penicillium sp. were cultured in the laboratory and tested for susceptibility to leaf extracts of the host plant and to proline, pipecolic acid, cis-5-hydroxypipecolic acid, and 2,4-trans-4,5-cis-4,5-dihydroxypipecolic acid. Fungal spore germination and germ tube growth were measured. Aspergillus sp. was inhibited by plant extracts and by pipecolic acid and cis-5-hydroxypipecolic acid. Curvularia sp. growth was stimulated by plant extracts and by pipecolic acid. The other two fungi were unaffected by any of the treatments. The data indicate that imino acids may play a role in the specific resistance of Calliandra spp. to Aspergillus sp. PMID:3707119

Brenner, S A; Romeo, J T

1986-01-01

257

Heparin and Its Non-Anticoagulant Analogues Inhibit Human Keratinocyte Growth Without Inducing Differentiation  

Microsoft Academic Search

In addition to its anti-coagulant effect, heparin inhibits the growth of several types of cells. Recent studies suggest that heparin inhibition of proliferation of cultured human keratinocytes results primarily from interaction with keratinocyte-generated, heparin-binding autocrine growth factors. In this study, we evaluated whether non-anticoagulant heparin analogs, and oligosaccharide fragments of heparin, retain the growth-inhibitory properties of whole heparin on human

Sreekumar Pillai; Lisa Gilliam; H. Edward Conrad; Walter M. Holleran

1994-01-01

258

Quercetin induces HepG2 cell apoptosis by inhibiting fatty acid biosynthesis  

PubMed Central

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

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

2014-01-01

259

Identification of organic acids in Cichorium intybus inhibiting virulence-related properties of oral pathogenic bacteria.  

PubMed

The low molecular mass (LMM) extract of Cichorium intybus var. silvestre (red chicory) has been shown to inhibit virulence-linked properties of oral pathogens including Streptococcus mutans, Actinomyces naeslundii and Prevotella intermedia. In the present study HPLC-DAD-ESI/MS(2) was used to investigate the compounds contained in this extract for their anti-virulence activity. The extract contained a number of components, including oxalic, succinic, shikimic and quinic acids, which interfere with the growth and virulence traits (i.e., biofilm formation, adherence to epithelial cells and hydroxyapatite) of oral pathogens involved in gingivitis and tooth decay. Succinic and quinic acid seem to be the most potent, mainly by interfering with the ability of oral pathogens to form biofilms (either through inhibition of their development or promotion of their disruption). Our findings suggest that one or more of these compounds may modulate plaque formation in vivo, which is a prerequisite for the development of both caries and gingivitis. PMID:23411301

Papetti, Adele; Mascherpa, Dora; Carazzone, Chiara; Stauder, Monica; Spratt, David A; Wilson, Michael; Pratten, Jonathan; Ciric, Lena; Lingström, Peter; Zaura, Egija; Weiss, Ervin; Ofek, Itzak; Signoretto, Caterina; Pruzzo, Carla; Gazzani, Gabriella

2013-06-01

260

Inhibition of Recombinant D-Amino Acid Oxidase from Trigonopsis variabilis by Salts  

PubMed Central

Inhibition of recombinant D-amino acid oxidase from Trigonopsis variabilis (TvDAAO) activity in the presence of different sodium salts and potassium chloride is reported. A competitive inhibition pattern by sodium chloride was observed, and an inhibition constant value of Ki = 85?mM was calculated. Direct connection of NaCl inhibition with FAD cofactor dissociation was confirmed by measuring the fluorescence of tryptophanyl residues of the holoenzyme. PMID:21423676

Kopf, Jessica; Hormigo, Daniel; García, José Luis; Acebal, Carmen; de la Mata, Isabel; Arroyo, Miguel

2011-01-01

261

Adsorption and corrosion inhibitive properties of some organic molecules on iron electrode in sulfuric acid  

Microsoft Academic Search

Adsorption and corrosion inhibitive properties of three different organic molecules: 2-naphthalenesulfonic acid, 2,7-naphthalenedisulfonic acid and 2-naphthol-3,6-disulfonic acid are investigated on Armco-iron electrode cathodically polarized, in 0.5 moldm?3 H2SO4 solution. The examinations show that the three organic molecules behave as a cathodic corrosion inhibitors. The inhibitive efficiency, changes with the number of functional groups substituted on benzene ring and increases with

Lj. M Vra?ar; D. M Draži?

2002-01-01

262

Proximity-dependent inhibition of growth of Mannheimia haemolytica by Pasteurella multocida.  

PubMed

Mannheimia haemolytica, Pasteurella multocida, and Bibersteinia trehalosi have been identified in the lungs of pneumonic bighorn sheep (BHS; Ovis canadensis). Of these pathogens, M. haemolytica has been shown to consistently cause fatal pneumonia in BHS under experimental conditions. However, M. haemolytica has been isolated by culture less frequently than the other bacteria. We hypothesized that the growth of M. haemolytica is inhibited by other bacteria in the lungs of BHS. The objective of this study was to determine whether P. multocida inhibits the growth of M. haemolytica. Although in monoculture both bacteria exhibited similar growth characteristics, in coculture with P. multocida there was a clear inhibition of growth of M. haemolytica. The inhibition was detected at mid-log phase and continued through the stationary phase. When cultured in the same medium, the growth of M. haemolytica was inhibited when both bacteria were separated by a membrane that allowed contact (pore size, 8.0 ?m) but not when they were separated by a membrane that limited contact (pore size, 0.4 ?m). Lytic bacteriophages or bactericidal compounds could not be detected in the culture supernatant fluid from monocultures of P. multocida or from P. multocida-M. haemolytica cocultures. These results indicate that P. multocida inhibits the growth of M. haemolytica by a contact- or proximity-dependent mechanism. If the inhibition of growth of M. haemolytica by P. multocida occurs in vivo as well, it could explain the inconsistent isolation of M. haemolytica from the lungs of pneumonic BHS. PMID:22798357

Bavananthasivam, Jegarubee; Dassanayake, Rohana P; Kugadas, Abirami; Shanthalingam, Sudarvili; Call, Douglas R; Knowles, Donald P; Srikumaran, Subramaniam

2012-09-01

263

Inhibition of bacterial growth under composite restorations following GLUMA pretreatment.  

PubMed

The purpose of this investigation was to test in five adult monkeys the effects of a glutaraldehyde-containing dentin bonding agent, GLUMA, on bacterial colonization in Class V cavities restored with composite resin. Experimental groups consisted of immediate placement of GLUMA and composite resin as well as placement of GLUMA or Scotchbond (control) in acid-etched cavities that had been left open to the oral environment for 48 hours. Various procedures for pretreatment of the cavities were included. Tissue specimens were prepared for light microscopy for observation of bacterial presence and pulp tissue reactions after eight days and 90 days. Bacteria were not detected in any of the 54 cavities treated with GLUMA regardless of observation period or use of enamel-etching procedure prior to placement of composite resin. When cavities were restored with composite resin without prior GLUMA pretreatment or with Scotchbond, bacteria were present under the majority of restorations at both time intervals. Pulpal inflammation of varying extent and character was seen after eight days in teeth that had been previously infected. At 90 days, pulps showed repair and healing regardless of treatment protocol. Data indicate that GLUMA has a distinct in vivo antibacterial effect that seems to prevent bacterial growth in tooth/restoration interfaces. PMID:2493491

Felton, D; Bergenholtz, G; Cox, C F

1989-03-01

264

3,5-Dihydroxybenzoic acid, a specific agonist for hydroxycarboxylic acid 1, inhibits lipolysis in adipocytes.  

PubMed

Niacin raises high-density lipoprotein and lowers low-density lipoprotein through the activation of the ?-hydroxybutyrate receptor hydroxycarboxylic acid 2 (HCA2) (aka GPR109a) but with an unwanted side effect of cutaneous flushing caused by vascular dilation because of the stimulation of HCA2 receptors in Langerhans cells in skin. HCA1 (aka GPR81), predominantly expressed in adipocytes, was recently identified as a receptor for lactate. Activation of HCA1 in adipocytes by lactate results in the inhibition of lipolysis, suggesting that agonists for HCA1 may be useful for the treatment of dyslipidemia. Lactate is a metabolite of glucose, suggesting that HCA1 may also be involved in the regulation of glucose metabolism. The low potency of lactate to activate HCA1, coupled with its fast turnover rate in vivo, render it an inadequate tool for studying the biological role of lactate/HCA1 in vivo. In this article, we demonstrate the identification of 3-hydroxybenzoic acid (3-HBA) as an agonist for both HCA2 and HCA1, whereas 3,5-dihydroxybenzoic acid (3,5-DHBA) is a specific agonist for only HCA1 (EC(50) ?150 ?M). 3,5-DHBA inhibits lipolysis in wild-type mouse adipocytes but not in HCA1-deficient adipocytes. Therefore, 3,5-DHBA is a useful tool for the in vivo study of HCA1 function and offers a base for further HCA1 agonist design. Because 3-HBA and 3,5-DHBA are polyphenolic acids found in many natural products, such as fruits, berries, and coffee, it is intriguing to speculate that other heretofore undiscovered natural substances may have therapeutic benefits. PMID:22434674

Liu, Changlu; Kuei, Chester; Zhu, Jessica; Yu, Jingxue; Zhang, Li; Shih, Amy; Mirzadegan, Taraneh; Shelton, Jonathan; Sutton, Steven; Connelly, Margery A; Lee, Grace; Carruthers, Nicholas; Wu, Jiejun; Lovenberg, Timothy W

2012-06-01

265

Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells  

NASA Technical Reports Server (NTRS)

It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

Hughes-Fulford, M.; Chen, Y.; Tjandrawinata, R. R.

2001-01-01

266

Inhibition of growth and alteration of host cell interactions of Pasteurella multocida with natural byproducts.  

PubMed

Pasteurella multocida is a leading cause of fowl cholera in both free-range pasture and conventional/commercially raised poultry. Its infection is a serious threat to poultry health and overall flock viability. Organic poultry is comparatively more vulnerable to this pathogen. It is a significant cause of production loss and price increase of poultry products, specifically organic poultry products. Some plant products are well documented as sources of natural antimicrobials such as polyphenols found in different berry pomaces and citrus oil. Pomace, a byproduct (primarily of seeds and skins) of fruits used for juice and wine production, and citrus oil, the byproduct of citrus juice production, show promising antimicrobial activity against various pathogens. Here, we showed for the first time that blackberry and blueberry pomace extracts and citrus oil inhibited P. multocida growth. Minimum bactericidal concentrations were determined as 0.3 and 0.4 mg/mL gallic acid equivalent for blackberry and blueberry pomace extracts, respectively. Similarly, only 0.05% citrus oil (vol/vol) completely inhibited P. multocida growth. Under shaking conditions, the antimicrobial activity of both pomace extracts and citrus oil was more intensive. Even citrus oil vapor also significantly reduced the growth of P. multocida. In addition, cell surface hydrophobicity of P. multocida was increased by 2- to 3-fold and its adherence to chicken fibroblast (DF1) and bovine mammary gland (MacT) cells was reduced significantly in the presence of pomace extracts only. This study indicates that these natural products might be good alternatives to conventional antimicrobial agents, and hence, may be used as feed or water supplements to control fowl cholera and reduce production loss caused by P. multocida. PMID:24879687

Salaheen, S; Almario, J A; Biswas, D

2014-06-01

267

Baicalein upregulates DDIT4 expression which mediates mTOR inhibition and growth inhibition in cancer cells.  

PubMed

Baicalein is a natural flavone that exhibits anticancer properties. Using microarrays we found that DDIT4 was the highest transcript induced by baicalein in cancer cells. We confirmed in multiple cancer cell lines large, dose-related expression of DDIT4 by quantitative RT-PCR and immunoblot, which correlates with growth inhibition. Time course experiments demonstrate that DDIT4 is rapidly inducible, with high expression maintained for several days in vitro. Induction of DDIT4 expression is p53 independent based on evaluation of p53 knockout cells. Since DDIT4 is known to inhibit mTORC1 activity we confirmed that baicalein suppresses phosphorylation of mTORC1 targets. Using RNA interference we demonstrate that mTORC1 activity and growth inhibition by baicalein is attenuated by knockdown of DDIT4. We furthermore demonstrate suppression of established tumors by baicalein in a mouse model of breast cancer with increased DDIT4 expression in the tumors. Finally, we demonstrate that baicalein upregulates DDIT4 and causes mTORC1 and growth inhibition in platinum resistant cancer cells in marked contrast to platinum chemotherapy treatment. These studies demonstrate that baicalein inhibits mTORC1 through DDIT4 expression, and may be useful in cancer chemotherapy and chemoprevention. PMID:25543165

Wang, Yujun; Han, Ernest; Xing, Quanhua; Yan, Jin; Arrington, Amanda; Wang, Charles; Tully, Dylan; Kowolik, Claudia M; Lu, David M; Frankel, Paul H; Zhai, Jing; Wen, Wei; Horne, David; Yip, M L Richard; Yim, John H

2015-03-28

268

Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth.  

PubMed

Propolis, a honey bee hive product, is thought to exhibit a broad spectrum of activities including antibiotic, antiviral, anti-inflammatory and tumor growth inhibition; some of the observed biological activities may be due to caffeic acid (cinnamic acid) esters that are present in propolis. In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma, HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium strains TA 98 and TA 100 plus S9 activation using 5 and 10 micrograms DMAB and antimutagenic activities of 0-150 microM MC, 0-60 microM PEC and 0-80 microM PEDMC were determined. The results indicate that MC, PEC and PEDMC were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity was significantly inhibited with 150 microM MC, 40-60 microM PEC and 40-80 microM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma cells with > 150 microM MC, 30 microM PEC and 20 microM PEDMC significantly inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK activities were also inhibited in HT-29 cells treated with different concentrations of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which are present in Propolis possess chemopreventive properties when tested in short-term assay systems. PMID:1423745

Rao, C V; Desai, D; Kaul, B; Amin, S; Reddy, B S

1992-11-16

269

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

SciTech Connect

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.

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

270

Action spectra for the inhibition of growth in radish hypocotyls  

Microsoft Academic Search

In etiolated seedlings of Raphanus sativus L. the inhibition of hypocotyl elongation by continuous light showed a major bimodal peak of action in the red and far-red, and two minor peaks in the blue regions of the spectrum. It is argued that, under conditions of prolonged irradiation, phytochrome is the pigment controlling the inhibition of hypocotyl elongation by red and

Ann M. Jose; Daphne Vince-Prue

1977-01-01

271

Eco friendly inhibitor for corrosion inhibition of mild steel in phosphoric acid medium  

Microsoft Academic Search

The inhibition effect of Zenthoxylum alatum plant extract on the corrosion of mild steel in 20, 50 and 88% aqueous orthophosphoric acid has been investigated by weight loss and electrochemical impedance spectroscopy (EIS). Plant extract is able to reduce the corrosion of steel more effectively in 88% phosphoric acid than in 20% phosphoric acid. The effect of temperature on the

G Gunasekaran; L. R Chauhan

2004-01-01

272

The adsorption and corrosion inhibition of anion surfactants on aluminium surface in hydrochloric acid  

Microsoft Academic Search

The adsorption and corrosion inhibition of the anion surfactants such as Dodecyl Sulphonic Acid Sodium Salt (DSASS), Dodecyl Benzene Sulfonic Acid Sodium Salt (DBSASS) and Sodium Dodecyl Sulfate (SDS) on the aluminium surface in hydrochloric acid solution was studied using the weight loss method. It was found that the adsorption of surfactants could prevent aluminum from weight loss and the

Tianpei Zhao; Guannan Mu

1999-01-01

273

Tolfenamic acid induces apoptosis and growth inhibition in anaplastic thyroid cancer: Involvement of nonsteroidal anti-inflammatory drug-activated gene-1 expression and intracellular reactive oxygen species generation.  

PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs) are usually used for the treatment of inflammatory diseases. However, certain NSAIDs also have antitumor activities in various cancers, including head and neck cancer, through cyclooxygenase-dependent or independent pathways. Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), a TGF-? superfamily protein, is induced by NSAIDs and has been shown to be induced by several antitumorigenic compounds and to exhibit proapoptotic and antitumorigenic activities. In this report, we demonstrate for the first time that tolfenamic acid (TA) transcriptionally induced the expression of NAG-1 during TA-induced apoptosis of anaplastic thyroid cancer (ATC) cells. TA reduced the viability of ATC cells in a dose-dependent manner and induced apoptosis, findings that were coincident with NAG-1 expression. Overexpression of the NAG-1 gene using cDNA enhanced the apoptotic effect of TA, whereas suppression of NAG-1 expression by small interfering RNA attenuated TA-induced apoptosis. Subsequently, we found that intracellular ROS generation plays an important role in activating the proapoptotic protein NAG-1. Then, we confirmed antitumorigenic effects of TA in a nude mouse orthotopic ATC model, and this result accompanied the augmentation of NAG-1 expression and ROS generation in tumor tissue. Taken together, these results demonstrate that TA induces apoptosis via NAG-1 expression and ROS generation in in vitro and in vivo ATC models, providing a novel mechanistic explanation and indicating a potential chemotherapeutic approach for treatment of ATC. PMID:24216474

Chang, Jae Won; Kang, Sung Un; Choi, Jae Won; Shin, Yoo Seob; Baek, Seung Joon; Lee, Seong-Ho; Kim, Chul-Ho

2014-02-01

274

Effects of polyunsaturated fatty acids on the growth of gastric cancer cells in vitro  

PubMed Central

Polyunsaturated fatty acids (PUFAs) have tumoricidal action, though the exact mechanism of their action is not clear. The results of the present study showed that of all the fatty acids tested, linoleic acid (LA) and ?-linolenic acid (ALA) were the most effective in suppressing the growth of normal gastric cells (GES1) at 180 and 200 ?M, while gastric carcinoma cells (MGC and SGC) were inhibited at 200 ?M. Arachidonic acid (AA) suppressed the growth of GES1, MGC and SGC cells and lower concentrations (120 and 160 ?M) of AA were more effective against gastric carcinoma (MGC and SGC) cells compared to normal gastric cells (GES1). Paradoxically, both eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids though are more unsaturated than AA, were less effective compared with LA, ALA and AA in suppressing the growth of both normal and cancer cells. At the concentration used, methotrexate showed much less growth suppressive action compared to all the fatty acids tested. PUFAs-treated cells showed accumulation of lipid droplets. A close association was noted between apoptosis and lipid peroxides formed compared to the ability of normal and tumor cells to generate ROS (reactive oxygen species) and induce SOD (superoxide dismutase activity) in response to fatty acids tested and methotrexate. Both normal and tumor cells generated lipoxin A4 (LXA4) in response to supplementation of fatty acids and methotrexate though no significant correlation was noted between their ability to induce apoptosis and LXA4 formed. These results suggest that PUFAs induced apoptosis of normal gastric and gastric carcinoma cells could, partly, be attributed to lipid peroxidation process. PMID:23663688

2013-01-01

275

Growth of nitric acid hydrates on thin sulfuric acid films  

Microsoft Academic Search

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 [times] 10[sup [minus]4] Torr H[sub 2]O and 1-2.5 [times] 10[sup [minus]6] Torr HNO[sub 3]) and subjected to cooling and heating cycles. FTIR spectroscopy was used to

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

1994-01-01

276

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

PubMed

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

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

2010-07-01

277

Growth changes of apple seedlings in response to simulated acid rain  

SciTech Connect

In a greenhouse experiment, Malus hupehensis seedlings were treated weekly with simulated acid rain solutions ranging from pH 2.25 to pH 7.0. Necrotic lesions developed on leaves at pH 2.25 and pH 2.50 immediately after the first application at the 8-node stage. Following the 9th weekly application on seedlings with 23 to 26 nodes, lesions developed at pH levels up to 3.25. At final destructive harvest, 20% of the leaf area at pH 2.25 and 8% of the leaf area at pH 2.50 was injured. Significant growth reduction occured at these 2 pH levels. Regression analysis indicated extensive growth inhibition at pH 3.0, no growth inhibition around pH 3.5, some inhibition between pH 4.5 and pH 5.6, and normal growth at pH 7.0 in comparison to the unsprayed control. Growth was negatively correlated with lesion formation at 3 destructive harvest dates.

Forsline, P.L.; Dee, R.J.; Melious, R.E.

1983-01-01

278

Tiaprofenic acid inhibits the renal reabsorption of sulfate in rats.  

PubMed

The objectives of the current investigation were: (1) to examine the effects of the nonsteroidal anti-inflammatory drug, tiaprofenic acid (TA), on sulfate renal reabsorption, and (2) to determine if concomitant prostaglandin E2 (PGE2) could reverse these effects. In crossover studies, female Lewis rats (n = 9) received either TA (as an intravenous (i.v.) bolus injection of 15 mg/kg and constant infusion of 0.02 mg/min) or its vehicle for 6 h. A blood sample was obtained at 5 h and urine was collected between 4 and 6 h. At a steady-state TA serum concentration of approximately 190 micrograms/ml, the PGE2 urinary excretion rate was inhibited by > 90% with no change in glomerular filtration rate (GFR), as measured by creatinine clearance. TA administration resulted in a significant decrease in serum sulfate concentrations (0.65 +/- 0.22 vs 1.1 +/- 0.15 mM, mean +/- SD, p < 0.01) and increase in sulfate clearance ratio (0.32 +/- 0.14 vs 0.13 +/- 0.06, p < 0.01) when compared to the vehicle-treated period. There was also a significant decrease in the fraction of sulfate reabsorbed by the kidneys (0.68 +/- 0.14 vs 0.87 +/- 0.06 in the vehicle-treated period, p < 0.01). In a second crossover study, rats received either TA or TA plus PGE2. PGE2 was administered as an infusion (0.1 micrograms/min) beginning 210 min after the start of the TA infusion. An additional group of rats served as controls and received both vehicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8361986

Benincosa, L J; Morris, M E

1993-07-01

279

Oleanolic acid inhibits proliferation and invasiveness of Kras-transformed cells via autophagy.  

PubMed

Oleanolic acid (OA) has been widely studied because of its pleiotropic therapeutic and preventive effect on various diseases. However, the mechanisms of OA's action are still not clear yet, especially its suppressing effect on transformed cells. In this work, we found that OA induced autophagy in normal tissue-derived cells without cytotoxicity. OA-induced autophagy was shown to decrease the proliferation of KRAS-transformed normal cells and to impair their invasion and anchorage-independent growth. Interrupting autophagy rescued OA's effect on the transformed cells. Mouse model experiments also demonstrated that OA suppressed the growth of KRAS-transformed breast epithelial cell MCF10A-derived tumor xenograft by inducing autophagy. Finally, we identified that OA induced autophagy in normal cells by inhibiting the activation of Akt/mTOR/S6K signaling. In conclusions, we found that OA treatment permitted normal cells to undergo autophagy. The induced autophagy was required for OA to prevent or delay the growth of transformed normal cells. PMID:25172632

Liu, Jia; Zheng, Lanhong; Ma, Leina; Wang, Bin; Zhao, Youguang; Wu, Ning; Liu, Ge; Lin, Xiukun

2014-11-01

280

Inhibition of Diabrotica Larval Growth by Patatin, the Lipid Acyl Hydrolase from Potato Tubers.  

PubMed Central

Patatin, the nonspecific lipid acyl hydrolase from potato (Solanum tuberosum L.) tubers, dose-dependently inhibits the growth of southern corn rootworm (SCR) and western corn rootworm when fed to them on artificial diet. The 50% growth reduction levels are somewhat cultivar dependent, ranging from 60 to 150 [mu]g/g diet for neonate SCR larvae. A single patatin isoform also inhibits larval growth. Neonate SCR continuously exposed to patatin are halted in larval development. Treatment with di-isopropylfluorophosphate essentially eliminates patatin's phospholipase, galactolipase, and acyl hydrolase activities. SCR growth inhibition is eliminated also, indicating that patatin's serine hydrolase activity is responsible for the observed activities. Patatin-mediated phospholipolysis is highly pH and cultivar dependent, with specific activities up to 300-fold less at pH 5.5 than at pH 8.5. Esterase or phospholipase activities do not correlate with insect growth inhibition. Galactolipase activity, being cultivar and pH independent, correlates significantly with SCR growth inhibition. Insect-growth inhibition of patatin is significantly reduced with increased dietary cholesterol levels. In conclusion, patatin represents a new class of insect-control proteins with a novel mode of action possibly involving lipid metabolism. PMID:12228621

Strickland, J. A.; Orr, G. L.; Walsh, T. A.

1995-01-01

281

Ursolic acid inhibits colorectal cancer angiogenesis through suppression of multiple signaling pathways.  

PubMed

Angiogenesis plays a critical role in the development of solid tumors by supplying nutrients and oxygen to support continuous growth of tumor as well as providing an avenue for hematogenous metastasis. Tumor angiogenesis is highly regulated by multiple intracellular signaling transduction cascades such as Hedgehog, STAT3, Akt and p70S6K pathways that are known to malfunction in many types of cancer including colorectal cancer (CRC). Therefore, suppression of tumor angiogenesis through targeting these signaling pathways has become a promising strategy for cancer chemotherapy. Ursolic acid (UA) is a major active compound present in many medicinal herbs that have long been used in China for the clinical treatment of various types of cancer. Although previous studies have demonstrated an antitumor effect for UA, the precise mechanisms of its anti-angiogenic activity are not well understood. To further elucidate the mechanism(s) of the tumorcidal activity of UA, using a CRC mouse xenograft model, chick embryo chorioallantoic membrane (CAM) model, the human colon carcinoma cell line HT-29 and human umbilical vein endothelial cells (HUVECs), in the present study we evaluated the efficacy of UA against tumor growth and angiogenesis in vivo and in vitro and investigated the underlying molecular mechanisms. We found that administration of UA significantly inhibited tumor volume but had no effect on body weight changes in CRC mice, suggesting that UA can suppress colon cancer growth in vivo without noticeable signs of toxicity. In addition, UA treatment reduced intratumoral microvessel density (MVD) in CRC mice, decreased the total number of blood vessels in the CAM model, and dose and time-dependently inhibited the proliferation, migration and tube formation of HUVECs, demonstrating UA's antitumor angiogenesis in vivo and in vitro. Moreover, UA treatment inhibited the expression of critical angiogenic factors, such as VEGF-A and bFGF. Furthermore, UA suppressed the activation of sonic hedgehog (SHH), STAT3, Akt and p70S6K pathways. Collectively, our findings suggest that inhibition of tumor angiogenesis via suppression of multiple signaling pathways might be one of the mechanisms whereby UA can be effective in cancer treatment. PMID:24042330

Lin, Jiumao; Chen, Youqin; Wei, Lihui; Hong, Zhenfeng; Sferra, Thomas J; Peng, Jun

2013-11-01

282

Transcription Factor Smad3 Is Required for the Inhibition of Adipogenesis by Retinoic Acid*  

PubMed Central

The process of adipocyte differentiation is driven by a highly coordinated cascade of transcriptional events that results in the development of the mature adipocyte and in lipid accumulation. One of the early events of differentiation is the up-regulation of CCAAT/enhancer-binding protein ? (C/EBP?) expression. C/EBP? then acts to up-regulate the expression of adipogenic factors such as C/EBP?, which control the late stage of adipogenesis. Retinoic acid (RA) is a potent inhibitor of adipogenesis, and its action appears to block C/EBP? transcriptional potential early during differentiation. Using preadipocytes and mesenchymal stem cell models, we show that RA specifically blocks the occupancy of C/EBP? of the Cebpa promoter, thereby abrogating the differentiation process. RA does not act directly on C/EBP? but rather stimulates the expression of the transforming growth factor ?-effector protein Smad3, which can interact with C/EBP? via its Mad homology 1 domain and can interfere with C/EBP? DNA binding. The RA-induced increase in Smad3 expression results in increased cytoplasmic and nuclear Smad3, an important event as ectopic expression of Smad3 in preadipocytes in the absence of RA treatment only modestly inhibits adipogenesis and C/EBP? DNA binding, suggesting that Smad3 alone is not sufficient to completely recapitulate the effects of retinoic acid treatment during differentiation. However, in the absence of Smad3, RA is not able to inhibit adipocyte differentiation or to elicit a decrease in C/EBP? DNA occupancy suggesting that Smad3 is necessary to convey the inhibitory effects of retinoic acid during adipogenesis. PMID:20179325

Marchildon, François; St-Louis, Catherine; Akter, Rahima; Roodman, Victoria; Wiper-Bergeron, Nadine L.

2010-01-01

283

Gellan sulfate inhibits Plasmodium falciparum growth and invasion of red blood cells in vitro  

PubMed Central

Here, we assessed the sulfated derivative of the microbial polysaccharide gellan gum and derivatives of ? and ?-carrageenans for their ability to inhibit Plasmodium falciparum 3D7 and Dd2 growth and invasion of red blood cells in vitro. Growth inhibition was assessed by means of flow cytometry after a 96-h exposure to the inhibitors and invasion inhibition was assessed by counting ring parasites after a 20-h exposure to them. Gellan sulfate strongly inhibited invasion and modestly inhibited growth for both P. falciparum 3D7 and Dd2; both inhibitory effects exceeded those achieved with native gellan gum. The hydrolyzed ?-carrageenan and oversulfated ?-carrageenan were less inhibitory than their native forms. In vitro cytotoxicity and anticoagulation assays performed to determine the suitability of the modified polysaccharides for in vivo studies showed that our synthesized gellan sulfate had low cytotoxicity and anticoagulant activity. PMID:24740150

Recuenco, Frances Cagayat; Kobayashi, Kyousuke; Ishiwa, Akiko; Enomoto-Rogers, Yukiko; Fundador, Noreen Grace V.; Sugi, Tatsuki; Takemae, Hitoshi; Iwanaga, Tatsuya; Murakoshi, Fumi; Gong, Haiyan; Inomata, Atsuko; Horimoto, Taisuke; Iwata, Tadahisa; Kato, Kentaro

2014-01-01

284

Mis-Regulation of 3-Deoxy-d-Arabino-Heptulosonate 7-Phosphate Synthetase Does Not Account for Growth Inhibition by Phenylalanine in Agmenellum quadruplicatum  

PubMed Central

The growth of the blue-green bacterium, Agmenellum quadruplicatum, is inhibited in the presence of l-phenylalanine. This species has a single, constitutively synthesized 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAHP) synthetase. l-Phenylalanine inhibits DAHP synthetase non-competitively with respect to both substrate reactants. Other aromatic amino acids do not inhibit the activity of DAHP synthetase. A common expectation for branch-point enzymes such as DAHP synthetase is a balanced pattern of feedback control by all of the ultimate end products. It seemed likely that growth inhibition might equate with defective regulation within the branched aromatic pathway. Accordingly, the possibility was examined that mis-regulation of DAHP synthetase by l-phenylalanine in wild-type cells causes starvation for precursors of the other aromatic end products. However, the molecular basis for growth inhibition cannot be attributed to l-phenylalanine inhibition of DAHP synthetase for the following reasons: (i) DAHP synthetase enzymes from l-phenylalanine-resistant mutants are more, rather than less, sensitive to feedback inhibition by l-phenylalanine. (ii) Shikimate not only fails to antagonize inhibition, but is itself inhibitory. (iii) Neither the sensitivity nor the completeness of l-phenylalanine inhibition of the wild-type enzyme in vitro appears sufficient to account for the potent inhibition of growth in vivo by l-phenylalanine. The dominating effect of l-phenylalanine in the control of DAHP synthetase appears to reflect a mechanism that prevents rather than causes growth inhibition by l-phenylalanine. The alteration of the control of DAHP synthetase in mutants selected for resistance to growth inhibition by l-phenylalanine did indicate that the cause for this metabolite vulnerability can be localized within the aromatic amino acid pathway. Apparently, an aromatic intermediate (between shikimate and the end products) accumulates in the presence of l-phenylalanine, causing toxicity by some unknown mechanism. It is concluded that phenylpyruvate, potentially formed by transamination of l-phenylalanine, is an unlikely cause of growth inhibition. Although several significant questions remain unanswered, our results suggest that single-effector control of DAHP synthetase, the first regulatory enzyme activity of a branched pathway, may be more appropriate than it would seem a priori. PMID:4215792

Jensen, Roy A.; Stenmark-Cox, S.; Ingram, Lonnie O.

1974-01-01

285

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

PubMed

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

Abusnina, A; Keravis, T; Zhou, Q; Justiniano, H; Lobstein, A; Lugnier, C

2015-01-27

286

Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts  

SciTech Connect

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.

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

287

New Symmetrically Esterified m-Bromobenzyl Non-Aminobisphosphonates Inhibited Breast Cancer Growth and Metastases  

PubMed Central

Background Although there was growing evidence in the potential use of Bisphosphonates (BPs) in cancer therapy, their strong osseous affinities that contrast their poor soft tissue uptake limited their use. Here, we developed a new strategy to overcome BPs hydrophilicity by masking the phosphonic acid through organic protecting groups and introducing hydrophobic functions in the side chain. Methodology/Principal Findings We synthesized non-nitrogen BPs (non N-BPs) containing bromobenzyl group (BP7033Br) in their side chain that were symmetrically esterified with hydrophobic 4-methoxphenyl (BP7033BrALK) and assessed their effects on breast cancer estrogen-responsive cells (T47D, MCF-7) as well as on non responsive ones (SKBR3, MDA-MB-231 and its highly metastatic derived D3H2LN subclone). BP7033Br ALK was more efficient in inhibiting tumor cell proliferation, migration and survival when compared to BP7033Br. Although both compounds inhibited tumor growth without side effects, only BP7033Br ALK abrogated tumor angiogenesis and D3H2LN cells-induced metastases formation. Conclusion/Significance Taken together these data suggest the potential therapeutic use of this new class of esterified Bisphosphonates (BPs) in the treatment of tumor progression and metastasis without toxic adverse effects. PMID:19262688

Abdelkarim, Mohamed; Guenin, Erwann; Sainte-Catherine, Odile; Vintonenko, Nadejda; Peyri, Nicole; Perret, Gerard Yves; Crepin, Michel; Khatib, Abdel-Majid; Lecouvey, Marc; Di Benedetto, Mélanie

2009-01-01

288

Influence of some growth regulators and cations on inhibition of chlorophyll biosynthesis by lead in maize  

SciTech Connect

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.

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

289

Growth inhibition of Streptococcus from the oral cavity by ?-amyrin esters.  

PubMed

Five terpenoids were tested by the macrodilution broth method to determine their inhibition activity on cariogenic bacterial growth. In general, ?-, ?-amyrin and ?-amyrin phenylacetate proved to be active, reducing the bacterial viability to less than 20%. PMID:23099616

Díaz-Ruiz, Gloria; Hernández-Vázquez, Liliana; Luna, Héctor; Wacher-Rodarte, María del Carmen; Navarro-Ocaña, Arturo

2012-01-01

290

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...

291

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

PubMed

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

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

2014-12-01

292

Trans fatty acids in hydrogenated fat inhibited the synthesis of the polyunsaturated fatty acids in the phospholipid of arterial cells  

Microsoft Academic Search

Our hypothesis that the trans fatty acids in hydrogenated fat inhibited the synthesis of polyunsaturated fatty acids in the phospholipid of arterial cells was tested with five groups each with six pregnant porcine fed from d 35 of gestation and during lactation. The basal diet contained 2% corn oil (control). The other four diets included the control +10% butter or

Fred A Kummerow; Qi Zhou; Mohamedain M Mahfouz; Michelle R Smiricky; Christine M Grieshop; David J Schaeffer

2004-01-01

293

Somatostatin Analogues Inhibit Growth of Pancreatic Cancer by Stimulating Tyrosine Phosphatase  

Microsoft Academic Search

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

C. Liebow; C. Reilly; M. Serrano; A. V. Schally

1989-01-01

294

Role of acids and bases in nanoparticle growth  

NASA Astrophysics Data System (ADS)

Secondary aerosol particles that are formed in atmosphere by gas-to-particle conversion during new particle formation events have potential to affect climate significantly due to their typically high number concentrations. This, however, requires that the freshly formed nanoparticles of about 1 nm in diameter grow tens of nanometers and reach climatically relevant sizes, i.e. sizes where they can act as cloud condensation nuclei. During the growth towards larger sizes the nanoparticles are subject to coagulational losses, and the rate at which the nanoparticles grow by condensation of vapors is a key factor affecting their probability to survive to climatically relevant sizes. Vapors that condense on the nanoparticles can be produced in the atmosphere from volatile compounds through gas phase chemical reactions, and their volatility can also be further lowered by particle phase processes. Therefore, particle composition and particle phase processes may influence nanoparticle growth. We study the growth of atmospheric nanoparticles and especially the role of particle phase salt formation in the nanoparticle growth using MABNAG model (Model for Acid-Base chemistry in NAnoparticle Growth) and by comparing to atmospheric measurements. MABNAG is a condensation growth model for aqueous solution particles. In MABNAG the dynamics of gas phase mass transport of vapors to particle are coupled with thermodynamics of particle phase acid-base chemistry, and both the composition and size dependence of equilibrium vapor pressures are accounted for. The model is applied especially for boreal forest environment. Here nanoparticle growth is modeled with a system of water, two acids (sulfuric acid and an organic acid) and two bases (ammonia and an amine) as condensing vapors. Focus is on the neutralization of acids by the bases and the related effects on the particle growth. According to the model predictions the enhancement of condensation of organic acid due to salt formation is dependent on the base concentrations and significant only at high-base conditions. However, for the sulfuric acid and the two bases acid-base chemistry is important. The growth rate of the particles is predicted to increase with increasing relative humidity, partly due to the increase in water mass but also partly due to the increase in condensation of the amine and the subsequent enhancement of condensation of the organic acid.

Yli-Juuti, Taina; Barsanti, Kelley; Bzdek, Bryan; Hildebrandt Ruiz, Lea; Jokinen, Tuija; Kieloaho, Antti-Jussi; Makkonen, Ulla; Petäjä, Tuukka; Ruuskanen, Taina; Johnston, Murray; Kulmala, Markku; Riipinen, Ilona

2014-05-01

295

Cytokinin antagonizes abscisic acid-mediated inhibition of cotyledon greening by promoting the degradation of abscisic acid insensitive5 protein in Arabidopsis.  

PubMed

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

Guan, Chunmei; Wang, Xingchun; Feng, Jian; Hong, Sulei; Liang, Yan; Ren, Bo; Zuo, Jianru

2014-03-01

296

Dynamic Adaption of Metabolic Pathways during Germination and Growth of Lily Pollen Tubes after Inhibition of the Electron Transport Chain1[W][OPEN  

PubMed Central

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

Obermeyer, Gerhard; Fragner, Lena; Lang, Veronika; Weckwerth, Wolfram

2013-01-01

297

Inhibition of Mycobacterial Growth In Vitro following Primary but Not Secondary Vaccination with Mycobacterium bovis BCG  

PubMed Central

Despite the widespread use of the Mycobacterium bovis BCG vaccine, there are more than 9 million new cases of tuberculosis (TB) every year, and there is an urgent need for better TB vaccines. TB vaccine candidates are selected for evaluation based in part on the detection of an antigen-specific gamma interferon (IFN-?) response. The measurement of mycobacterial growth in blood specimens obtained from subjects immunized with investigational TB vaccines may be a better in vitro correlate of in vivo vaccine efficacy. We performed a clinical study with 30 United Kingdom adults who were followed for 6 months to evaluate the abilities of both a whole-blood- and a novel peripheral blood mononuclear cell (PBMC)-based mycobacterial growth inhibition assay to measure a response to primary vaccination and revaccination with BCG. Using cryopreserved PBMCs, we observed a significant improvement in mycobacterial growth inhibition following primary vaccination but no improvement in growth inhibition following revaccination with BCG (P < 0.05). Mycobacterial growth inhibition following primary BCG vaccination was not correlated with purified protein derivative (PPD) antigen-specific IFN-? enzyme-linked immunospot (ELISPOT) responses. We demonstrate that a mycobacterial growth inhibition assay can detect improved capacity to control growth following primary immunization, but not revaccination, with BCG. This is the first study to demonstrate that an in vitro growth inhibition assay can identify a difference in vaccine responses by comparing both primary and secondary BCG vaccinations, suggesting that in vitro growth inhibition assays may serve as better surrogates of clinical efficacy than the assays currently used for the assessment of candidate TB vaccines. PMID:23986316

Fletcher, Helen A.; Tanner, Rachel; Wallis, Robert S.; Meyer, Joel; Manjaly, Zita-Rose; Harris, Stephanie; Satti, Iman; Silver, Richard F.; Hoft, Dan; Kampmann, Beate; Walker, K. Barry; Dockrell, Hazel M.; Fruth, Uli; Barker, Lew; McShane, Helen

2013-01-01

298

Ascorbic acid participates in a general mechanism for concerted glucose transport inhibition and lactate transport stimulation  

Microsoft Academic Search

In this paper, we present a novel function for ascorbic acid. Ascorbic acid is an important water-soluble antioxidant and\\u000a cofactor in various enzyme systems. We have previously demonstrated that an increase in neuronal intracellular ascorbic acid\\u000a is able to inhibit glucose transport in cortical and hippocampal neurons. Because of the presence of sodium-dependent vitamin\\u000a C transporters, ascorbic acid is highly

Maite A. Castro; Constanza Angulo; Sebastián Brauchi; Francisco Nualart; Ilona I. Concha

2008-01-01

299

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

PubMed

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 strains TH1 and 8MF2 were inhibitory. In contrast, when biomass of strains WT, TH1, and 8MF2 was autoclaved and incorporated at 1%, shoot fresh weight was promoted, but the biomass of T35 was inhibitory. None of the strains incorporated at 0.1 % w/w increased shoot fresh weight, and autoclaved biomass of TH1, T35, and 20 incorporated at 0.1% w/w resulted in lower shoot fresh weights in comparison with uninoculated controls. The shoot dry weight of lettuce seedlings could be enhanced by germinating seeds in uninoculated compost and after five days' growth transferring them into WT-inoculated compost. Inoculum of strain TH1 when applied using this method was very inhibitory. With WT the degree of increase in shoot fresh weight and germination rate declined as the fermentation time to produce inocula was increased. PMID:24190096

Ousley, M A; Lynch, J M; Whipps, J M

1993-11-01

300

Inhibition of fatty acid delta 6- and delta 5-desaturation by cyclopropene fatty acids in rat liver microsomes.  

PubMed

delta 6-Desaturation of linoleic acid and delta 5-desaturation of dihomo-gamma-linolenic acid were measured in liver microsomes from rats fed fresh Baobab seed oil containing cyclopropene fatty acids (malvalic acid and sterculic acid) or heated Baobab seed oil practically devoid of these fatty acids or control oil. The presence of cyclopropene fatty acids in the fresh Baobab oil diet highly depressed both desaturations, but delta 6- more than delta 5-desaturation. The decreased capacity of microsomes to desaturate was reflected in the lower arachidonic acid content in microsomal phospholipids from rats fed this oil. However it was also lower in rats fed heated oil although in vitro delta 6- and delta 5-desaturation were not depressed. When liver microsomes prepared from rats fed the control diet were used for the desaturation assays, the presence of free malvalic or sterculic acid in the medium, also highly depressed delta 6- and delta 5-desaturation. The incorporation of arachidonic acid, the product of delta 5-desaturation, into phospholipids was also highly depressed, while that of the precursor dihomo-gamma-linolenic acid was not. This suggests that cyclopropene fatty acids specifically inhibit incorporation of the delta 5-desaturation product into phospholipids or that they specifically inhibit desaturation of the substrate previously incorporated into a membrane phospholipid. PMID:7903050

Cao, J; Blond, J P; Bézard, J

1993-12-01

301

Ammonia oxidation-dependent growth of group I.1b Thaumarchaeota in acidic red soil microcosms.  

PubMed

Accumulating evidence suggests that Thaumarchaeota may control nitrification in acidic soils. However, the composition of the thaumarchaeotal communities and their functioning is not well known. Therefore, we studied nitrification activity in relation to abundance and composition of Thaumarchaeota in an acidic red soil from China, using microcosms incubated with and without cellulose amendment. Cellulose was selected to simulate the input of crop residues used to increase soil fertility by local farming. Accumulation of NO3-(-N) was correlated with the growth of Thaumarchaeota as determined by qPCR of 16S rRNA and ammonia monooxygenase (amoA) genes. Both nitrification activity and thaumarchaeotal growth were inhibited by acetylene. They were also inhibited by cellulose amendment, possibly due to the depletion of ammonium by enhanced heterotrophic assimilation. These results indicated that growth of Thaumarchaeota was dependent on ammonia oxidation. The thaumarchaeotal 16S rRNA gene sequences in the red soil were dominated by a clade related to soil fosmid clone 29i4 within the group I.1b, which is widely distributed but so far uncultured. The archaeal amoA sequences were mainly related to the Nitrososphaera sister cluster. These observations suggest that fosmid clone 29i4 and Nitrososphaera sister cluster represent the same group of Thaumarchaeota and dominate ammonia oxidation in acidic red soil. PMID:24724989

Wu, Yucheng; Conrad, Ralf

2014-07-01

302

Corrosion inhibition of steel in concrete by carboxylic acids  

Microsoft Academic Search

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

K. K. Sagoe-Crentsil; F. P. Glasser; V. T. Yilmaz

1993-01-01

303

Branched-Chain Amino Acid Biosynthesis Is Essential for Optimal Growth of Streptococcus thermophilus in Milk  

PubMed Central

Lactic acid bacteria are nutritionally demanding bacteria which need, among other things, amino acids for optimal growth. We identified the branched-chain amino acid (BCAA) biosynthesis pathway as an essential pathway for optimal growth of Streptococcus thermophilus in milk. Through random insertional mutagenesis, we isolated and characterized two mutants for which growth in milk is affected as a consequence of ilvB and ilvC gene interruptions. This situation demonstrates that the BCAA biosynthesis pathway is active in S. thermophilus. BCAA biosynthesis is necessary but not sufficient for optimal growth of S. thermophilus and is subject to retro-inhibition processes. The specificity of the BCAA biosynthesis pathway in S. thermophilus lies in the independent transcription of the ilvC gene encoding a keto acid reductoisomerase acting on acetolactate at the junction of the BCAA and acetoin biosynthesis pathways. The possible advantages for S. thermophilus of keeping this biosynthesis pathway active could be linked either to adaptation of the organism to milk, which is different than that of other dairy bacteria, or to the role of the pathway in maintaining the internal pH. PMID:11097879

Garault, P.; Letort, C.; Juillard, V.; Monnet, V.

2000-01-01

304

Corrosion inhibition of mild steel in acidic media by some organic dyes  

Microsoft Academic Search

The inhibitive capabilities of some organic dyes namely; safranine-o (SO), thymol blue (TB) and fluorescein-Na (F-Na) on the electrochemical corrosion of mild steel in sulphuric acid solution was rapidly assessed using the gasometric technique. The results indicate that all of the studied compounds act as inhibitors in the acidic corrodent. Inhibition efficiency increased with concentration for SO and TB but

E. E. Ebenso; E. E. Oguzie

2005-01-01

305

Modelling the effect of lactic acid bacteria from starter- and aroma culture on growth of Listeria monocytogenes in cottage cheese.  

PubMed

Four mathematical models were developed and validated for simultaneous growth of mesophilic lactic acid bacteria from added cultures and Listeria monocytogenes, during chilled storage of cottage cheese with fresh- or cultured cream dressing. The mathematical models include the effect of temperature, pH, NaCl, lactic- and sorbic acid and the interaction between these environmental factors. Growth models were developed by combining new and existing cardinal parameter values. Subsequently, the reference growth rate parameters (?ref at 25°C) were fitted to a total of 52 growth rates from cottage cheese to improve model performance. The inhibiting effect of mesophilic lactic acid bacteria from added cultures on growth of L. monocytogenes was efficiently modelled using the Jameson approach. The new models appropriately predicted the maximum population density of L. monocytogenes in cottage cheese. The developed models were successfully validated by using 25 growth rates for L. monocytogenes, 17 growth rates for lactic acid bacteria and a total of 26 growth curves for simultaneous growth of L. monocytogenes and lactic acid bacteria in cottage cheese. These data were used in combination with bias- and accuracy factors and with the concept of acceptable simulation zone. Evaluation of predicted growth rates of L. monocytogenes in cottage cheese with fresh- or cultured cream dressing resulted in bias-factors (Bf) of 1.07-1.10 with corresponding accuracy factor (Af) values of 1.11 to 1.22. Lactic acid bacteria from added starter culture were on average predicted to grow 16% faster than observed (Bf of 1.16 and Af of 1.32) and growth of the diacetyl producing aroma culture was on average predicted 9% slower than observed (Bf of 0.91 and Af of 1.17). The acceptable simulation zone method showed the new models to successfully predict maximum population density of L. monocytogenes when growing together with lactic acid bacteria in cottage cheese. 11 of 13 simulations of L. monocytogenes growth were within the acceptable simulation zone, which demonstrated good performance of the empirical inter-bacterial interaction model. The new set of models can be used to predict simultaneous growth of mesophilic lactic acid bacteria and L. monocytogenes in cottage cheese during chilled storage at constant and dynamic temperatures. The applied methodology is likely to be applicable for safety prediction of other types of fermented and unripened dairy products where inhibition by lactic acid bacteria is important for growth of pathogenic microorganisms. PMID:25086348

Østergaard, Nina Bjerre; Eklöw, Annelie; Dalgaard, Paw

2014-10-01

306

Inhibition of free radical-induced erythrocyte hemolysis by 2- O-substituted ascorbic acid derivatives  

Microsoft Academic Search

Inhibitory effects of 2-O-substituted ascorbic acid derivatives, ascorbic acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S), on 2,2?-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of sheep erythrocytes were studied and were compared with those of ascorbic acid (AA) and other antioxidants. The order of the inhibition efficiency was AA-2S?Trolox=uric acid?AA-2P?AA-2G=AA>glutathione. Although the reactivity of the AA derivatives against

Jun Takebayashi; Hiroaki Kaji; Kenji Ichiyama; Kazutaka Makino; Eiichi Gohda; Itaru Yamamoto; Akihiro Tai

2007-01-01

307

Effect of the Folic Acid Analogue, Trimethoprim, on Growth, Macromolecular Synthesis, and Incorporation of Exogenous Thymine in Escherichia coli1  

PubMed Central

The effect of trimethoprim [2,4-diamino-5(2?,4?,5?trimethoxybenzyl)-pyrimidine] in the presence of thymine on Escherichia coli B temperature-sensitive and non-temperature-sensitive Thy? strains and a phosphodeoxyribomutase-negative mutant was studied. The inhibitory effect of 5 ?g of trimethoprim per ml on the growth of E. coli B was not overcome by thymine, thymidine, or thymidylate even in the presence of one-carbon metabolites and related metabolites. Deoxyribonucleic acid (DNA) and protein synthesis were more severely inhibited than ribonucleic acid (RNA) synthesis. The inhibition of DNA synthesis was partially reversed by addition of deoxyadenosine to increase the incorporation of exogenous thymine. By contrast, the inhibition of protein was not reversed even with one-carbon metabolites present, in keeping with the requirement for formylmethionyl-transfer RNAF for initiation. However, the inhibition of both DNA and protein synthesis in a phosphodeoxyribomutase-negative strain by 1 ?g of trimethoprim per ml with thymine present was partially reversed by deoxyadenosine and one-carbon metabolites, and nearly normal growth occurred. 5-Fluorodeoxyuridine added at the time of addition of trimethoprim prevented the inhibition. Sulfadiazine in the presence of thymine inhibited both Thy+ and Thy? strains whereas trimethoprim (with thymine) did not inhibit Thy? organisms. The effect of trimethoprim on the incorporation of labeled thymine into DNA was also studied. These experiments support the concept that trimethoprim in conjunction with the action of thymidylate synthetase inhibits the growth of Thy+ cells because of a depletion of tetrahydrofolate. DNA synthesis is inhibited initially by a limitation of thymine nucleotide precursor, resulting from the indirect inhibition of thymidylate synthetase and the poor incorporation of exogenous thymine. PMID:4260561

Dale, Beverly A.; Greenberg, G. Robert

1972-01-01

308

Mixotrophic growth of Phaeodactylum tricornutum on glycerol: growth rate and fatty acid profile  

Microsoft Academic Search

Mixotrophic growth of the eicosapentaenoic acid (EPA) producing diatom Phaeodactylum tricornutumUTEX 640 was carried out in 1-L batch cultures under an external irradiance of 165mol photons m 2 s 1 by supplementing the inorganic culture medium with glycerol. The effect on the growth and the fatty acid profile was studied for different initial glycerol concentrations (0-0.1 M). The optimal glycerol

M. C. Cer; J. M. Fernandez Sevilla; F. G. Aci; E. Molina Grim; F. Gar

309

A role for AMPK in the inhibition of glucose-6-phosphate dehydrogenase by polyunsaturated fatty acids  

SciTech Connect

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.

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

310

Zafirlukast Inhibits Complexation of Lsr2 with DNA and Growth of Mycobacterium tuberculosis  

PubMed Central

The mycobacterial nucleoid-associated protein Lsr2 is a DNA-bridging protein that plays a role in condensation and structural organization of the genome and acts as a global repressor of gene transcription. Here we describe experiments demonstrating that zafirlukast inhibits the complexation between Lsr2 and DNA in vitro. Zafirlukast is shown to inhibit growth in two different species of mycobacteria tested but exhibits no growth inhibition of Escherichia coli. The Lsr2 inhibitory activity is reflected in vivo as determined by monitoring of transcription levels in Mycobacterium tuberculosis. These data suggest that zafirlukast inhibits Lsr2 function in vivo, promoting dysregulation of the expression of an array of genes typically bound by Lsr2 and hindering growth. Since zafirlukast likely operates by a mechanism distinct from current M. tuberculosis drugs and is currently used as a prophylactic treatment for asthma, it offers an intriguing lead for development of new treatments for tuberculosis. PMID:23439641

Pinault, Lucile; Han, Jeong-Sun; Kang, Choong-Min; Franco, Jimmy

2013-01-01

311

Modeling the Effect of Abrupt Acid and Osmotic Shifts within the Growth Region and across Growth Boundaries on Adaptation and Growth of Listeria monocytogenes?  

PubMed Central

This study aims to model the effects of acid and osmotic shifts on the intermediate lag time of Listeria monocytogenes at 10°C in a growth medium. The model was developed from data from a previous study (C. I. A. Belessi, Y. Le Marc, S. I. Merkouri, A. S. Gounadaki, S. Schvartzman, K. Jordan, E. H. Drosinos, and P. N. Skandamis, submitted for publication) on the effects of osmotic and pH shifts on the kinetics of L. monocytogenes. The predictive ability of the model was assessed on new data in milk. The effects of shifts were modeled through the dependence of the parameter h0 (“work to be done” prior to growth) induced on the magnitude of the shift and/or the stringency of the new environmental conditions. For shifts across the boundary, the lag time was found to be affected by the length of time for which the microorganisms were kept at growth-inhibiting conditions. The predicted concentrations of L. monocytogenes in milk were overestimated when the effects of this shift were not taken into account. The model proved to be suitable to describe the effects of osmotic and acid shifts observed both within the growth domain and across the growth boundaries of L. monocytogenes. PMID:20675449

Le Marc, Y.; Skandamis, P. N.; Belessi, C. I. A.; Merkouri, S. I.; George, S. M.; Gounadaki, A. S.; Schvartzman, S.; Jordan, K.; Drosinos, E. H.; Baranyi, J.

2010-01-01

312

THE INFLUENCE OF MAGNETIC FIELDS ON INHIBITION OF MCF-7 CELL GROWTH BY TAMOXIFEN  

EPA Science Inventory

THE INFLUENCE OF MAGNETIC FIELDS ON INHIBITION OF MCF-7 CELL GROWTH BY TAMOXIFEN. Harland and Liburdy (1) reported that 1.2-uT, 60-Hz magnetic fields could significantly block the inhibitory action of pharmacological levels of tamoxifen (10-7 M) on the growth of MCF-7 human br...

313

Water logging may inhibit plant growth primarily by nutrient deficiency rather than nutrient toxicity  

Microsoft Academic Search

The aim of our experiments was to investigate whether nutrient deficiency or toxicity is the cause for growth inhi - bition of wheat and barley in waterlogged soils. Experiments using two soils (top and subsoil) differing largely in various characteristics revealed a growth inhibition of wheat and barley in the case of subsoil due to water logging, without Fe or

D. Steffens; B. W. Hütsch; T. Eschholz; T. Lošák; S. Schubert; Justus Liebig

2005-01-01

314

An interfacial energy mechanism for the complete inhibition of crystal growth by inhibitor adsorption  

E-print Network

is that the adsorption of inhibitor leads to a reduction in interfacial tension or edge energy for the crystal surface or to a reduction in growth rate. The inhibition of crystal growth due to adsorption is impor- tant for both natural subcoolings.1,2 For the prevention of hydrate formation dur- ing the production of natural gas, the premium

Firoozabadi, Abbas

315

Extracts of Acacia farnesiana and Artemisia ludoviciana inhibit growth, enterotoxin production and adhesion of Vibrio cholerae  

Microsoft Academic Search

Summary  Extracts of 32 medicinal plants commonly used in Mexico were evaluated for their effects on the growth of Vibrio cholerae strains O1 and O139. Of these, the ethanolic extracts of Acacia farnesiana and Artemisia ludoviciana effectively inhibited bacterial growth. The effects of these plant extracts on enterotoxin production and adhesion of V. cholerae to Chinese hamster ovary (CHO) cells were

Santos García; Ginebra Alarcón; Cristina Rodríguez; Norma Heredia

2006-01-01

316

Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence  

PubMed Central

Inhibition of growth signaling pathways protects against aging and age-related diseases in parallel with reduced oxidative stress. The relationships between growth signaling, oxidative stress and aging remain unclear. Here we report that in Saccharomyces cerevisiae, alterations in growth signaling pathways impact levels of superoxide anions that promote chronological aging and inhibit growth arrest of stationary phase cells in G0/G1. Factors that decrease intracellular superoxide anions in parallel with enhanced longevity and more efficient G0/G1 arrest include genetic inactivation of growth signaling pathways that inhibit Rim15p, which activates oxidative stress responses, and downregulation of these pathways by caloric restriction. Caloric restriction also reduces superoxide anions independently of Rim15p by elevating levels of H2O2, which activates superoxide dismutases. In contrast, high glucose or mutations that activate growth signaling accelerate chronological aging in parallel with increased superoxide anions and reduced efficiency of stationary phase G0/G1 arrest. High glucose also activates DNA damage responses and preferentially kills stationary phase cells that fail to arrest growth in G0/G1. These findings suggest that growth signaling promotes chronological aging in budding yeast by elevating superoxide anions that inhibit quiescence and induce DNA replication stress. A similar mechanism likely contributes to aging and age-related diseases in complex eukaryotes. PMID:21076178

Weinberger, Martin; Mesquita, Ana; Carroll, Timothy; Marks, Laura; Yang, Hui; Zhang, Zhaojie; Ludovico, Paula; Burhans, William C.

2010-01-01

317

Gyramides Prevent Bacterial Growth by Inhibiting DNA Gyrase and Altering Chromosome Topology  

E-print Network

Gyramides Prevent Bacterial Growth by Inhibiting DNA Gyrase and Altering Chromosome Topology that the gyramides prevent bacterial growth by a mechanism in which the topological state of chromosomes is altered-century, and the emergence of bacterial resistance has fueled the search for new gyrase inhibitors. In this paper we

Weibel, Douglas B.

318

Farnesyltransferase inhibitor R115777 inhibits cell growth and induces apoptosis in Mantle Cell Lymphoma  

E-print Network

of the farnesyltranseferase inhibitor R115777 was evaluated in cell lines representative of mantle cell lymphoma (MCL). Cell growth, proliferation, and apoptosis were analyzed in four human MCL cell lines (Granta, NCEB, REC mice xenografted with UPN1 cells. R115777 inhibited the growth of MCL cell lines in vitro

Paris-Sud XI, Université de

319

2,3-Dihydroxybenzoic Acid-Containing Nanofiber Wound Dressings Inhibit Biofilm Formation by Pseudomonas aeruginosa  

PubMed Central

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

Ahire, Jayesh J.

2014-01-01

320

Growth and graviresponsiveness of primary roots of Zea mays seedlings deficient in abscisic acid and gibberellic acid  

NASA Technical Reports Server (NTRS)

The objective of this research was to determine if gibberellic acid (GA) and/or abscisic acid (ABA) are necessary for graviresponsiveness by primary roots of Zea mays. To accomplish this objective we measured the growth and graviresponsiveness of primary roots of seedlings in which the synthesis of ABA and GA was inhibited collectively and individually by genetic and chemical means. Roots of seedlings treated with Fluridone (an inhibitor of ABA biosynthesis) and Ancymidol (an inhibitor of GA biosynthesis) were characterized by slower growth rates but not significantly different gravicultures as compared to untreated controls. Gravicurvatures of primary roots of d-5 mutants (having undetectable levels of GA) and vp-9 mutants (having undectable levels of ABA) were not significantly different from those of wild-type seedlings. Roots of seedlings in which the biosynthesis of ABA and GA was collectively inhibited were characterized by gravicurvatures not significantly different for those of controls. These results (1) indicate that drastic reductions in the amount of ABA and GA in Z. mays seedlings do not significantly alter root graviresponsiveness, (2) suggest that neither ABA nor GA is necessary for root gravicurvature, and (3) indicate that root gravicurvature is not necessarily proportional to root elongation.

Moore, R.; Dickey, K.

1985-01-01

321

A Chemokine Receptor Antagonist Inhibits Experimental Breast Tumor Growth  

Microsoft Academic Search

The leukocyte infiltrate of human and murine epithelial cancers is regulated by chemokine production in the tumor microenvironment. In this article, we tested the hypothesis that chemokine receptor antagonists may have anticancer activity by inhibiting this infiltrate. We first char- acterized CC chemokines, chemokine receptors, and the leukocyte infil- trate in the 410.4 murine model of breast cancer. We found

Stephen C. Robinson; Kate A. Scott; Julia L. Wilson; Richard G. Thompson; Amanda E. I. Proudfoot; Frances R. Balkwill

2003-01-01

322

Effect of acetyl 11-keto beta-boswellic acid on metastatic growth factor responsible for angiogenesis.  

PubMed

Basic fibroblast growth factor (bFGF), a metastatic growth factor is known to be one of the promoting factors in the tumor induced angiogenesis. The antiangiogenic activity of acetyl 11-keto beta-boswellic acid was screened against bFGF-induced angiogenesis using in-vivo Matrigel Plug Assay. Histological & colorimetric examination confirmed that numerous blood vessels were present in Matrigel+bFGF group in comparison to Matrigel alone treated mice. Acetyl 11-keto beta-boswellic acids (10 mg/kg/d) inhibited the Matrigel+bFGF-induced angiogenesis significantly (P<0.01) in contrast to anti-inflammatory agent indomethacin (10 mg/kg/d) and alkylating agent cyclophosphamide (10 mg/kg/d). PMID:17257903

Singh, Shashank Kumar; Bhusari, Sachin; Singh, Reena; Saxena, Ajit; Mondhe, Dilip; Qazi, Ghulam Nabi

2007-05-01

323

Methyl anthranilate and ?-decalactone inhibit strawberry pathogen growth and achene Germination.  

PubMed

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

Chambers, Alan H; Evans, Shane Alan; Folta, Kevin M

2013-12-26

324

Plant growth inhibitory activity of Ophiopogon japonicus Ker-Gawler and role of phenolic acids and their analogues: a comparative study  

Microsoft Academic Search

Allelopathic potential of Ophiopogon japonicus was investigated. The methanolic extract of O. japonicus roots strongly inhibited root and hypocotyls growth of lettuce. Sequential partitioning of the methanol extract with organic solvents showed that the diethyl ether and n-butanol extract possess strong plant growth inhibitory activities. The allelopathic constituents of the diethyl ether extract were isolated and identified as salicylic acid

Zahida Iqbal; Syuntaro Hiradate; Hiroshi Araya; Yoshiharu Fujii

2004-01-01

325

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

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

Shinsuke Kuwaki; Iichiro Ohhira; Masumi Takahata; Atsuko Hirota; Yoshiyuki Murata; Mikiro Tada

2004-01-01

326

Vanadate inhibition of fungal phyA and bacterial appA2 histidine acid phosphatases  

Technology Transfer Automated Retrieval System (TEKTRAN)

The fungal PhyA protein, which was first identified as an acid optimum phosphomonoesterase (EC 3.1.3.8), could also serve as a vanadate haloperoxidase (EC 1.11.1.10) provided the acid phosphatase activity is shutdown by vanadate. To understand how vanadate inhibits both phytate and pNPP degrading ac...

327

Effect of soluble epoxide hydrolase inhibition on epoxyeicosatrienoic acid metabolism in human blood vessels  

E-print Network

blood vessels Xiang Fang,1 Neal L. Weintraub,2,3,4 Ryan B. McCaw,1 Shanming Hu,1 Shawn D. Harmon,1 James on epoxyeicosatrienoic acid metabolism in human blood vessels. Am J Physiol Heart Circ Physiol 287: H2412­H2420, 2004 epoxide hydrolase (sEH) inhibition on epoxyei- cosatrienoic acid (EET) metabolism in intact human blood

Hammock, Bruce D.

328

Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation.  

PubMed

Many protein misfolding diseases, for example, Alzheimer's, Parkinson's and Huntington's, are characterised by the accumulation of protein aggregates in an amyloid fibrillar form. Natural products which inhibit fibril formation are a promising avenue to explore as therapeutics for the treatment of these diseases. In this study we have shown, using in vitro thioflavin T assays and transmission electron microscopy, that grape seed extract inhibits fibril formation of kappa-casein (?-CN), a milk protein which forms amyloid fibrils spontaneously under physiological conditions. Among the components of grape seed extract, gallic acid was the most active component at inhibiting ?-CN fibril formation, by stabilizing ?-CN to prevent its aggregation. Concomitantly, gallic acid significantly reduced the toxicity of ?-CN to pheochromocytoma12 cells. Furthermore, gallic acid effectively inhibited fibril formation by the amyloid-beta peptide, the putative causative agent in Alzheimer's disease. It is concluded that the gallate moiety has the fibril-inhibitory activity. PMID:24157371

Liu, Yanqin; Pukala, Tara L; Musgrave, Ian F; Williams, Danielle M; Dehle, Francis C; Carver, John A

2013-12-01

329

Mechanism of iron inhibition by stearic acid Langmuir-Blodgett monolayers  

SciTech Connect

Many organic compounds can be adsorbed onto the interface of a metal and solution to form a thin film that inhibits the corrosion process according to a blocking and/or negative catalytic effect. Using the Langmuir-Blodgett (LB) technique, stearic acid (SA) monolayers were deposited onto the surface of an iron (Fe) electrode to study the inhibition effect and the mechanism of SA in a neutral medium. Molecular orientation and the number of deposited monolayers of SA were shown to have marked effects on inhibition of Fe corrosion. The inhibition mechanism depended mainly on blocking.

Xing, W.; Shan, Y.; Guo, D.; Lu, T.; Xi, S. [Chinese Academy of Sciences, Changchun (China). Lab. of Electroanalytical Chemistry

1995-01-01

330

Bibersteinia trehalosi inhibits the growth of Mannheimia haemolytica by a proximity-dependent mechanism.  

PubMed

Mannheimia (Pasteurella) haemolytica is the only pathogen that consistently causes severe bronchopneumonia and rapid death of bighorn sheep (BHS; Ovis canadensis) under experimental conditions. Paradoxically, Bibersteinia (Pasteurella) trehalosi and Pasteurella multocida have been isolated from BHS pneumonic lungs much more frequently than M. haemolytica. These observations suggest that there may be an interaction between these bacteria, and we hypothesized that B. trehalosi overgrows or otherwise inhibits the growth of M. haemolytica. Growth curves (monoculture) demonstrated that B. trehalosi has a shorter doubling time ( approximately 10 min versus approximately 27 min) and consistently achieves 3-log higher cell density (CFU/ml) compared to M. haemolytica. During coculture M. haemolytica growth was inhibited when B. trehalosi entered stationary phase (6 h) resulting in a final cell density for M. haemolytica that was 6 to 9 logs lower than expected with growth in the absence of B. trehalosi. Coculture supernatant failed to inhibit M. haemolytica growth on agar or in broth, indicating no obvious involvement of lytic phages, bacteriocins, or quorum-sensing systems. This observation was confirmed by limited growth inhibition of M. haemolytica when both pathogens were cultured in the same media but separated by a filter (0.4-microm pore size) that limited contact between the two bacterial populations. There was significant growth inhibition of M. haemolytica when the populations were separated by membranes with a pore size of 8 mum that allowed free contact. These observations demonstrate that B. trehalosi can both outgrow and inhibit M. haemolytica growth with the latter related to a proximity- or contact-dependent mechanism. PMID:20038698

Dassanayake, Rohana P; Call, Douglas R; Sawant, Ashish A; Casavant, N Carol; Weiser, Glen C; Knowles, Donald P; Srikumaran, Subramaniam

2010-02-01

331

The metalloendopeptidase nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF).  

PubMed Central

Nardilysin (N-arginine dibasic convertase, or NRDc) is a cytosolic and cell-surface metalloendopeptidase that, in vitro, cleaves substrates upstream of Arg or Lys in basic pairs. NRDc differs from most of the other members of the M16 family of metalloendopeptidases by a 90 amino acid acidic domain (DAC) inserted close to its active site. At the cell surface, NRDc binds heparin-binding epidermal growth factor-like growth factor (HB-EGF) and enhances HB-EGF-induced cell migration. An active-site mutant of NRDc fulfills this function as well as wild-type NRDc, indicating that the enzyme activity is not required for this process. We now demonstrate that NRDc starts at Met(49). Furthermore, we show that HB-EGF not only binds to NRDc but also potently inhibits its enzymic activity. NRDc-HB-EGF interaction involves the 21 amino acid heparin-binding domain (P21) of the growth factor, the DAC of NRDc and most probably its active site. Only disulphide-bonded P21 dimers are inhibitory. We also show that Ca(2+), via the DAC, regulates both NRDc activity and HB-EGF binding. We conclude that the DAC is thus a key regulatory element for the two distinct functions that NRDc fulfills, i.e. as an HB-EGF modulator and a peptidase. PMID:12095415

Hospital, Véronique; Nishi, Eiichiro; Klagsbrun, Michael; Cohen, Paul; Seidah, Nabil G; Prat, Annik

2002-01-01

332

Salicylic acid inhibits enzymatic browning of fresh-cut Chinese chestnut (Castanea mollissima) by competitively inhibiting polyphenol oxidase.  

PubMed

The inhibitory effect and associated mechanisms of salicylic acid (SA) on the browning of fresh-cut Chinese chestnut were investigated. Shelled and sliced chestnuts were immersed in different concentrations of an SA solution, and the browning of the chestnut surface and interior were inhibited. The activities of polyphenol oxidase (PPO) and peroxidase (POD) extracted from chestnuts were measured in the presence and absence of SA. SA at concentrations higher than 0.3g/L delayed chestnut browning by significantly inhibiting the PPO activity (P<0.01), and the POD activity was not significantly affected (P>0.05). The binding and inhibition modes of SA with PPO and POD, determined by AUTODOCK 4.2 and Lineweaver-Burk plots, respectively, established SA as a competitive inhibitor of PPO. PMID:25308637

Zhou, Dan; Li, Lin; Wu, Yanwen; Fan, Junfeng; Ouyang, Jie

2015-03-15

333

Australian plants with potential to inhibit bacteria and processes involved in ruminal biohydrogenation of fatty acids  

Microsoft Academic Search

Conjugated linoleic acids (CLA) are health-promoting fatty acids found in foods derived from ruminant products that are formed in the rumen during bacterial biohydrogenation of linoleic acid (LA). Although selective antimicrobials might increase CLA production by manipulation of ruminal microflora, feeding of antibiotic growth promoters to livestock is declining due to fears of development of antibiotic resistance in human pathogens.

Z. Durmic; C. S. McSweeney; G. W. Kemp; P. Hutton; R. J. Wallace; P. E. Vercoe

2008-01-01

334

BRD4 Inhibitor Inhibits Colorectal Cancer Growth and Metastasis  

PubMed Central

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

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

335

Bithionol inhibits ovarian cancer cell growth In Vitro - studies on mechanism(s) of action  

PubMed Central

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

2014-01-01

336

Salicylhydroxamic acid (SHAM) inhibition of the dissolved inorganic carbon concentrating process in unicellular green algae  

SciTech Connect

Rates of photosynthetic O{sub 2} evolution, for measuring K{sub 0.5}(CO{sub 2} + HCO{sub 3}{sup {minus}}) at pH 7, upon addition of 50 micromolar HCO{sub 3}{sup {minus}} to air-adapted Chlamydomonas, Dunaliella, or Scenedesmus cells, were inhibited up to 90% by the addition of 1.5 to 4.0 millimolar salicylhydroxamic acid (SHAM) to the aqueous medium. The apparent K{sub i}(SHAM) for Chlamydomonas cells was about 2.5 millimolar, but due to low solubility in water effective concentrations would be lower. Salicylhydroxamic acid did not inhibit oxygen evolution or accumulation of bicarbonate by Scenedesmus cells between pH 8 to 11 or by isolated intact chloroplasts from Dunaliella. Thus, salicylhydroxamic acid appears to inhibit CO{sub 2} uptake, whereas previous results indicate that vanadate inhibits bicarbonate uptake. These conclusions were confirmed by three test procedures with three air-adapted algae at pH 7. Salicylhydroxamic acid inhibited the cellular accumulation of dissolved inorganic carbon, the rate of photosynthetic O{sub 2} evolution dependent on low levels of dissolved inorganic carbon (50 micromolar NaHCO{sub 3}), and the rate of {sup 14}CO{sub 2} fixation with 100 micromolar ({sup 14}C)HCO{sub 3}{sup {minus}}. Salicylhydroxamic acid inhibition of O{sub 2} evolution and {sup 14}CO{sub 2}-fixation was reversed by higher levels of NaHCO{sub 3}. Thus, salicylhydroxamic acid inhibition was apparently not affecting steps of photosynthesis other than CO{sub 2} accumulation. Although salicylhydroxamic acid is an inhibitor of alternative respiration in algae, it is not known whether the two processes are related.

Goyal, A.; Tolbert, N.E. (Michigan State Univ., East Lansing (USA))

1990-03-01

337

Corrosion inhibition of indole-3-acetic acid on mild steel in 0.5 M HCl  

Microsoft Academic Search

Corrosion inhibition of indole-3-acetic acid on mild steel in acidic medium (0.5M HCl) containing the desired amount of inhibitor has been investigated at different temperatures by using potentiodynamic polarization, electrochemical impedance spectroscopy, and polarization resistance measurements. The experimental results showed that corrosion potential shifted toward a more negative potential region in the presence of indole-3-acetic acid than that of blank

Gül?en Avci

2008-01-01

338

Growth changes of apple seedlings in response to simulated acid rain  

SciTech Connect

In a greenhouse experiment, Malus hupehensis (Pamp.) Rehd. seedlings were treated weekly with simulated acid rain solutions ranging from pH 2.25 to ph 7.0. Necrotic lesions developed on leaves at pH 2.25 and pH 2.50 immediately after the first application at the 8-node stage. Following the 9th weekly application on seedlings with 23 to 26 nodes, lesions developed at pH levels up to 3.25. At final destructive harvest, 20% of the leaf area at pH 2.25 and 8% of the leaf area at pH 2.50 was injured. Significant growth reduction occured at these 2 pH levels. Regression analysis indicated extensive growth inhibition at growth inhibition around pH 3.5, some inhibition between pH 4.5 and pH 5.6, and normal growth at pH 7.0 in comparison to the unsprayed control. Growth was negatively correlated with lesion formation at 3 destructive harvest dates. Relative growth rates were reduced only at pH 2.25 and pH 2.50 and reduction in the unit leaf rate was also observed. Lesion development continued to increase on the basal leaves through the 6th weekly application but leveled off during the final applications. Negative correlations of photosynthesis rate to lesion percentage and dry weight to lesion percentage were observed.

Forsline, P.L.; Dee, R.J.; Melious, R.E.

1983-01-01

339

Lifespan Based Pharmacokinetic-Pharmacodynamic Model of Tumor Growth Inhibition by Anticancer Therapeutics  

PubMed Central

Accurate prediction of tumor growth is critical in modeling the effects of anti-tumor agents. Popular models of tumor growth inhibition (TGI) generally offer empirical description of tumor growth. We propose a lifespan-based tumor growth inhibition (LS TGI) model that describes tumor growth in a xenograft mouse model, on the basis of cellular lifespan T. At the end of the lifespan, cells divide, and to account for tumor burden on growth, we introduce a cell division efficiency function that is negatively affected by tumor size. The LS TGI model capability to describe dynamic growth characteristics is similar to many empirical TGI models. Our model describes anti-cancer drug effect as a dose-dependent shift of proliferating tumor cells into a non-proliferating population that die after an altered lifespan TA. Sensitivity analysis indicated that all model parameters are identifiable. The model was validated through case studies of xenograft mouse tumor growth. Data from paclitaxel mediated tumor inhibition was well described by the LS TGI model, and model parameters were estimated with high precision. A study involving a protein casein kinase 2 inhibitor, AZ968, contained tumor growth data that only exhibited linear growth kinetics. The LS TGI model accurately described the linear growth data and estimated the potency of AZ968 that was very similar to the estimate from an established TGI model. In the case study of AZD1208, a pan-Pim inhibitor, the doubling time was not estimable from the control data. By fixing the parameter to the reported in vitro value of the tumor cell doubling time, the model was still able to fit the data well and estimated the remaining parameters with high precision. We have developed a mechanistic model that describes tumor growth based on cell division and has the flexibility to describe tumor data with diverse growth kinetics. PMID:25333487

Mo, Gary; Gibbons, Frank; Schroeder, Patricia; Krzyzanski, Wojciech

2014-01-01

340

Vitamin K enhancement of sorafenib-mediated HCC cell growth inhibition in vitro and in vivo.  

PubMed

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

Wei, Gang; Wang, Meifang; Hyslop, Terry; Wang, Ziqiu; Carr, Brian I

2010-12-15

341

Vitamin K enhancement of Sorafenib-mediated HCC cell growth inhibition in vitro and in vivo  

PubMed Central

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

Wei, Gang; Wang, Meifanf; Hyslop, Terry; Wang, Ziqiu; Carr, Brian I.

2010-01-01

342

Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma  

PubMed Central

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

Lamoureux, Francois; Baud'huin, Marc; Ory, Benjamin; Guiho, Romain; Zoubeidi, Amina; Gleave, Martin; Heymann, Dominique; Rédini, Françoise

2014-01-01

343

Antiandrogenic activity of anthranilic acid ester derivatives as novel lead structures to inhibit prostate cancer cell proliferation.  

PubMed

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

Roell, Daniela; Rösler, Thomas W; Degen, Stephanie; Matusch, Rudolf; Baniahmad, Aria

2011-06-01

344

Corrosion inhibition and adsorption behavior of methionine on mild steel in sulfuric acid and synergistic effect of iodide ion  

Microsoft Academic Search

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

E. E. Oguzie; Y. Li; F. H. Wang

2007-01-01

345

Copper corrosion inhibition by triphenylmethane derivatives in sulphuric acid media  

Microsoft Academic Search

Triphenylmethane derivatives, namely fuchsin basic (FB) and fuchsin acid (FA), were studied for their possible use as copper corrosion inhibitors in 0.001 to 1.0 M sulphuric acid solutions. Benzotriazole (BTA) was also tested for comparative purposes. These inhibitors were studied in concentrations from 1×10?5 to 1×10?1 M at temperatures from 298 to 328 K. The gravimetric method was employed to

J. M. Bastidas; P. Pinilla; E. Cano; J. L. Polo; S. Miguel

2003-01-01

346

Indole3-butyric acid in plant growth and development  

Microsoft Academic Search

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

Jutta Ludwig-Müller

2000-01-01

347

Alpha Cyano-4-Hydroxy-3-Methoxycinnamic Acid Inhibits Proliferation and Induces Apoptosis in Human Breast Cancer Cells  

PubMed Central

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

Hamdan, Lamia; Arrar, Zoheir; Al Muataz, Yacoub; Suleiman, Lutfi; Négrier, Claude; Mulengi, Joseph Kajima; Boukerche, Habib

2013-01-01

348

Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells.  

PubMed

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

Hamdan, Lamia; Arrar, Zoheir; Al Muataz, Yacoub; Suleiman, Lutfi; Négrier, Claude; Mulengi, Joseph Kajima; Boukerche, Habib

2013-01-01

349

Effects of simulated acid rain on seedling emergence and growth of five broad-leaved species  

Microsoft Academic Search

Seeds and seedlings of five broad-leaved species were separately exposed to simulated acid rain at pH values of 2.0, 3.5,\\u000a 5.0, and 6.0, or to distilled water (the control). The results showed that seed germination was remarkably inhibited by pH\\u000a 2.0 treatment for three species. Significant foliar damage, decline in chlorophyll contents, and retardation of the seedlings\\u000a growth of all

Fan Houbao; Li Chuanrong

1999-01-01

350

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...

351

Inhibition of Mold Growth by Sourdough Bread Cultures  

Microsoft Academic Search

Sourdough bread cultures are mixtures of wild yeasts and Lactobacillus bacteria living in flour and water, where they form an interesting symbiosis that makes the culture quite stable. The presence of lactic acid bacteria (LAB) in sourdough bread cultures increases the shelf life of the sourdough bread and other sweet baked goods made with these cultures, due to the inhibitory

Pei Ven Kam; Andreia Bianchini; Lloyd B Bullerman

2007-01-01

352

Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation.  

PubMed

Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. PMID:24326154

Lamy, Sylvie; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R

2014-03-10

353

Ursodeoxycholic Acid but Not Tauroursodeoxycholic Acid Inhibits Proliferation and Differentiation of Human Subcutaneous Adipocytes  

PubMed Central

Stress of endoplasmic reticulum (ERS) is one of the molecular triggers of adipocyte dysfunction and chronic low inflammation accompanying obesity. ERS can be alleviated by chemical chaperones from the family of bile acids (BAs). Thus, two BAs currently used to treat cholestasis, ursodeoxycholic and tauroursodeoxycholic acid (UDCA and TUDCA), could potentially lessen adverse metabolic effects of obesity. Nevertheless, BAs effects on human adipose cells are mostly unknown. They could regulate gene expression through pathways different from their chaperone function, namely through activation of farnesoid X receptor (FXR) and TGR5, G-coupled receptor. Therefore, this study aimed to analyze effects of UDCA and TUDCA on human preadipocytes and differentiated adipocytes derived from paired samples of two distinct subcutaneous adipose tissue depots, abdominal and gluteal. While TUDCA did not alter proliferation of cells from either depot, UDCA exerted strong anti-proliferative effect. In differentiated adipocytes, acute exposition to neither TUDCA nor UDCA was able to reduce effect of ERS stressor tunicamycin. However, exposure of cells to UDCA during whole differentiation process decreased expression of ERS markers. At the same time however, UDCA profoundly inhibited adipogenic conversion of cells. UDCA abolished expression of PPAR? and lipogenic enzymes already in the early phases of adipogenesis. This anti-adipogenic effect of UDCA was not dependent on FXR or TGR5 activation, but could be related to ability of UDCA to sustain the activation of ERK1/2 previously linked with PPAR? inactivation. Finally, neither BAs did lower expression of chemokines inducible by TLR4 pathway, when UDCA enhanced their expression in gluteal adipocytes. Therefore while TUDCA has neutral effect on human preadipocytes and adipocytes, the therapeutic use of UDCA different from treating cholestatic diseases should be considered with caution because UDCA alters functions of human adipose cells. PMID:24312631

Mališová, Lucia; Ková?ová, Zuzana; Koc, Michal; Kra?merová, Jana; Štich, Vladimír; Rossmeislová, Lenka

2013-01-01

354

Ursodeoxycholic acid but not tauroursodeoxycholic acid inhibits proliferation and differentiation of human subcutaneous adipocytes.  

PubMed

Stress of endoplasmic reticulum (ERS) is one of the molecular triggers of adipocyte dysfunction and chronic low inflammation accompanying obesity. ERS can be alleviated by chemical chaperones from the family of bile acids (BAs). Thus, two BAs currently used to treat cholestasis, ursodeoxycholic and tauroursodeoxycholic acid (UDCA and TUDCA), could potentially lessen adverse metabolic effects of obesity. Nevertheless, BAs effects on human adipose cells are mostly unknown. They could regulate gene expression through pathways different from their chaperone function, namely through activation of farnesoid X receptor (FXR) and TGR5, G-coupled receptor. Therefore, this study aimed to analyze effects of UDCA and TUDCA on human preadipocytes and differentiated adipocytes derived from paired samples of two distinct subcutaneous adipose tissue depots, abdominal and gluteal. While TUDCA did not alter proliferation of cells from either depot, UDCA exerted strong anti-proliferative effect. In differentiated adipocytes, acute exposition to neither TUDCA nor UDCA was able to reduce effect of ERS stressor tunicamycin. However, exposure of cells to UDCA during whole differentiation process decreased expression of ERS markers. At the same time however, UDCA profoundly inhibited adipogenic conversion of cells. UDCA abolished expression of PPAR? and lipogenic enzymes already in the early phases of adipogenesis. This anti-adipogenic effect of UDCA was not dependent on FXR or TGR5 activation, but could be related to ability of UDCA to sustain the activation of ERK1/2 previously linked with PPAR? inactivation. Finally, neither BAs did lower expression of chemokines inducible by TLR4 pathway, when UDCA enhanced their expression in gluteal adipocytes. Therefore while TUDCA has neutral effect on human preadipocytes and adipocytes, the therapeutic use of UDCA different from treating cholestatic diseases should be considered with caution because UDCA alters functions of human adipose cells. PMID:24312631

Mališová, Lucia; Ková?ová, Zuzana; Koc, Michal; Kra?merová, Jana; Stich, Vladimír; Rossmeislová, Lenka

2013-01-01

355

The secreted glycoprotein CREG inhibits cell growth dependent on the mannose-6-phosphate/insulin-like growth factor II receptor.  

PubMed

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

Di Bacco, Alessandra; Gill, Grace

2003-08-21

356

Epoxygenase metabolites of arachidonic acid inhibit vasopressin response in toad bladder  

SciTech Connect

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.

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

357

Acid-catalyzed reactions of epoxides for atmospheric nanoparticle growth.  

PubMed

Although new particle formation accounts for about 50% of the global aerosol production in the troposphere, the chemical species and mechanism responsible for the growth of freshly nucleated nanoparticles remain largely uncertain. Here we show large size growth when sulfuric acid nanoparticles of 4-20 nm are exposed to epoxide vapors, dependent on the particle size and relative humidity. Composition analysis of the nanoparticles after epoxide exposure reveals the presence of high molecular weight organosulfates and polymers, indicating the occurrence of acid-catalyzed reactions of epoxides. Our results suggest that epoxides play an important role in the growth of atmospheric newly nucleated nanoparticles, considering their large formation yields from photochemical oxidation of biogenic volatile organic compounds. PMID:25338124

Xu, Wen; Gomez-Hernandez, Mario; Guo, Song; Secrest, Jeremiah; Marrero-Ortiz, Wilmarie; Zhang, Annie L; Zhang, Renyi

2014-11-01

358

Hydroperoxide lyase products, hexanal, hexenal and nonenal, inhibit soybean seedling growth  

SciTech Connect

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.

Gardner, H.W.; Dornbos, D.L. Jr. (Dept. of Agriculture, Peoria, IL (USA))

1989-04-01

359

CD43 Promotes Cells Transformation by Preventing Merlin-Mediated Contact Inhibition of Growth  

PubMed Central

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

Camacho-Concha, Nohemi; Olivos-Ortiz, Amiel; Nuñez-Rivera, Alfredo; Pedroza-Saavedra, Adolfo; Gutierrez-Xicotencatl, Lourdes; Rosenstein, Yvonne; Pedraza-Alva, Gustavo

2013-01-01

360

Inhibition of vitamin B12-dependent microbial growth by nitrous oxide  

SciTech Connect

In methionine-free media, nitrous oxide inhibits the growth of an auxotrophic strain of Escherichia coli lacking a cobalamin-independent pathway for the de novo synthesis of methionine. Prototrophic E. coli is similarly inhibited by nitrous oxide if the cobalamin-independent pathway is selectively depressed by sulfanilamide. Nitrous oxide thus effectively inactivates cobalamin-dependent 5-methyltetrahydrofolate-homocysteine methyltransferase in intact bacteria.

Alston, T.A. (Massachusetts General Hospital, Boston (USA))

1991-01-01

361

A systems chemical biology study of malate synthase and isocitrate lyase inhibition in Mycobacterium tuberculosis during active and NRP growth.  

PubMed

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 persistence 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

May, Elebeoba E; Leitão, Andrei; Tropsha, Alexander; Oprea, Tudor I

2013-12-01

362

Protease Inhibition by Oleic Acid Transfer From Chronic Wound Dressings to Albumin  

SciTech Connect

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.

Edwards, J. V.; Howley, Phyllis; Davis, Rachel M.; Mashchak, Andrew D.; Goheen, Steven C.

2007-08-01

363

Fatty acid synthase inhibition results in a magnetic resonance-detectable drop in phosphocholine  

PubMed Central

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

Ross, James; Najjar, Amer M.; Sankaranarayanapillai, Madhuri; Tong, William P.; Kaluarachchi, Kumaralal; Ronen, Sabrina M.

2008-01-01

364

Inhibition of the Indole?3?acetic acid?induced Epinastic Curvature in Tobacco Leaf Strips by 2,4?Dichlorophenoxyacetic Acid  

PubMed Central

It has been reported that auxin induces an epinastic growth response in plant leaf tissues. Leaf strips of tobacco (Nicotiana tabacum L. ‘Bright Yellow 2’) were used to study the effects of indole?3?acetic acid (IAA), the principal form of auxin in higher plants, and a synthetic auxin, 2,4?dichlorophenoxyacetic acid (2,4?D), on epinastic leaf curvature. Incubation of leaf strips with 10 µm IAA resulted in a marked epinastic curvature response. Unexpectedly, 2,4?D showed only a weak IAA?like activity in inducing epinasty. Interestingly, the presence of 2,4?D resulted in inhibition of the IAA?dependent epinastic curvature. In vivo Lineweaver–Burk kinetic analysis clearly indicated that the interaction between IAA and 2,4?D reported here is not a result of competitive inhibition. Using kinetic analysis, it was not possible to determine whether the mode of interaction between IAA and 2,4?D was non?competitive or uncompetitive. 2,4?D inhibits the IAA?dependent epinasty via complex and as yet unidentified mechanisms. PMID:12588726

KAWANO, NAKAKO; KAWANO, TOMONORI; LAPEYRIE, FREDERIC

2003-01-01

365

The inhibition of free radical generation by human neutrophils through the synergistic effects of metronidazole with palmitoleic acid: a possible mechanism of action of metronidazole in rosacea and acne  

Microsoft Academic Search

Metronidazole is clinically effective in treating not only rosacea but also acne inflammation. Yet it is generally considered not to be very effective in inhibiting the growth of anaerobic Propionibacterium acnes. We report here our investigation into the synergistic effects of metronidazole and palmitoleic acid on the anaerobic growth of P. acnes as well as on human neutrophil functions, including

H. Akamatsu; M. Oguchi; S. Nishijima; Y. Asada; M. Takahashi; T. Ushijima; Y. Niwa

1990-01-01

366

Inhibition of Alanine Aminotransferase in Silico and in Vivo Promotes Mitochondrial Metabolism to Impair Malignant Growth*  

PubMed Central

Cancer cells commonly exhibit increased nonoxidative d-glucose metabolism whereas induction of mitochondrial metabolism may impair malignant growth. We have first used an in silico method called elementary mode analysis to identify inhibition of ALAT (l-alanine aminotransferase) as a putative target to promote mitochondrial metabolism. We then experimentally show that two competitive inhibitors of ALAT, l-cycloserine and ?-chloro-l-alanine, inhibit l-alanine production and impair d-glucose uptake of LLC1 Lewis lung carcinoma cells. The latter inhibition is linked to an initial energy deficit, as quantified by decreased ATP content, which is then followed by an activation of AMP-activated protein kinase and subsequently increased respiration rates and mitochondrial production of reactive oxygen species, culminating in ATP replenishment in ALAT-inhibited LLC1 cells. Moreover, we observe altered phosphorylation of p38 MAPK (mitogen-activated protein kinase 14), ERK (extracellular signal-regulated kinase 1/2), and Rb1 (retinoblastoma 1) proteins, as well as decreased expression of Cdc25a (cell decision cycle 25 homolog A) and Cdk4 (cyclin-dependent kinase 4). Importantly, these sequelae of ALAT inhibition culminate in similarly reduced anchorage-dependent and anchorage-independent growth rates of LLC1 cells, together suggesting that inhibition of ALAT efficiently impairs cancer growth by counteracting the Warburg effect due to compensatory activation of mitochondrial metabolism. PMID:21540181

Beuster, Gregor; Zarse, Kim; Kaleta, Christoph; Thierbach, René; Kiehntopf, Michael; Steinberg, Pablo; Schuster, Stefan; Ristow, Michael

2011-01-01

367

Inhibition of alanine aminotransferase in silico and in vivo promotes mitochondrial metabolism to impair malignant growth.  

PubMed

Cancer cells commonly exhibit increased nonoxidative D-glucose metabolism whereas induction of mitochondrial metabolism may impair malignant growth. We have first used an in silico method called elementary mode analysis to identify inhibition of ALAT (L-alanine aminotransferase) as a putative target to promote mitochondrial metabolism. We then experimentally show that two competitive inhibitors of ALAT, L-cycloserine and ?-chloro-L-alanine, inhibit L-alanine production and impair D-glucose uptake of LLC1 Lewis lung carcinoma cells. The latter inhibition is linked to an initial energy deficit, as quantified by decreased ATP content, which is then followed by an activation of AMP-activated protein kinase and subsequently increased respiration rates and mitochondrial production of reactive oxygen species, culminating in ATP replenishment in ALAT-inhibited LLC1 cells. Moreover, we observe altered phosphorylation of p38 MAPK (mitogen-activated protein kinase 14), ERK (extracellular signal-regulated kinase 1/2), and Rb1 (retinoblastoma 1) proteins, as well as decreased expression of Cdc25a (cell decision cycle 25 homolog A) and Cdk4 (cyclin-dependent kinase 4). Importantly, these sequelae of ALAT inhibition culminate in similarly reduced anchorage-dependent and anchorage-independent growth rates of LLC1 cells, together suggesting that inhibition of ALAT efficiently impairs cancer growth by counteracting the Warburg effect due to compensatory activation of mitochondrial metabolism. PMID:21540181

Beuster, Gregor; Zarse, Kim; Kaleta, Christoph; Thierbach, René; Kiehntopf, Michael; Steinberg, Pablo; Schuster, Stefan; Ristow, Michael

2011-06-24

368

Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth factor  

Microsoft Academic Search

· Background: Ocular diseases caused by neovascularization are among the leading causes of blindness. No specific pharmacological\\u000a treatment is available. Among potential drugs, thalidomide deserves special interest since a wide body of clinical experience\\u000a exists. However, its antiangiogenic effect is controversial. We therefore investigated the effect of thalidomide on corneal\\u000a angiogenesis induced by vascular endothelial growth factor (VEGF), which has

Friedrich E. Kruse; Antonia M. Joussen; Klaus Rohrschneider; Matthias D. Becker; Hans E. Völcker

1998-01-01

369

Growth of Francisella tularensis LVS in macrophages: the acidic intracellular compartment provides essential iron required for growth.  

PubMed

Murine macrophages supported exponential intracellular growth of Francisella tularensis LVS in vitro with a doubling time of 4 to 6 h. LVS was internalized and remained in a vacuolar compartment throughout its growth cycle. The importance of endosome acidification to intracellular growth of this bacterium was assessed by treatment of LVS-infected macrophages with several different lysosomotropic agents (chloroquine, NH4Cl, and ouabain). Regardless of the agent used or its mechanism of action, macrophages treated with agents that blocked endosome acidification no longer supported replication of LVS. Over several experiments for each lysosomotropic agent, the number of CFU of LVS recovered from treated macrophage cultures was equivalent to the input inoculum (approximately 10(4) CFU) at 72 h. In contrast, over 10(8) CFU was consistently recovered from untreated cultures. Pretreatment of macrophages with these endosome acidification inhibitors did not alter their ingestion of bacteria. Further, the effects of the inhibitors were completely reversible: inhibitor-pretreated LVS-infected macrophages washed free of the agent and cultured in medium fully supported LVS growth over 72 h. Endosome acidification is an important cellular event essential for release of iron from transferrin. The growth-inhibitory effects of both chloroquine and NH4Cl were completely reversed by addition of ferric PPi, a transferrin-independent iron source, at a neutral pH but not by addition of excess holotransferrin. Thus, intracellular localization in an acidic vesicle which facilitates the availability of iron essential for Francisella growth is a survival tactic of this bacterium, and iron depletion is one mechanism that macrophages use to inhibit its growth. PMID:7890413

Fortier, A H; Leiby, D A; Narayanan, R B; Asafoadjei, E; Crawford, R M; Nacy, C A; Meltzer, M S

1995-04-01

370

Free fatty acids inhibit the activity of Clostridium histolyticum collagenase and human neutrophil elastase.  

PubMed

We investigated the ability of free fatty acids to inhibit the activity of Clostridium histolyticum collagenase (EC 3.4.24.3) and human neutrophil elastase (EC 3.4.21.37). We determined the activity of collagenase by degradation of resorufin-labeled casein fluorimetrically. The determination of the elastase activity was performed by a spectrophotometric method using a 4-nitroanilide peptide substrate. We found that most of the tested fatty acids inhibited collagenase at concentrations between 50 microM and 500 microM. For elastase we found an inhibition of the activity at concentrations between 500 nM and 50 microM. The most potent inhibitory fatty acids of both enzymes differed. Thus, as a result for collagenase we can assume that the saturated fatty acids with C(16)-C(19) were the most potent ones. For elastase the inhibition rate of unsaturated acids was much higher than the rate of the saturated ones. The highly active erucic acid with an IC(50) value of 450 nM (elastase) is remarkable. PMID:12357383

Rennert, Beate; Melzig, Matthias F

2002-09-01

371

AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis  

PubMed Central

The cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. In particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. We found that the energy regulator AMPK, which potently inhibits fatty acid synthesis, restricts infection of the Bunyavirus, Rift Valley Fever Virus (RVFV), an important re-emerging arthropod-borne human pathogen for which there are no effective vaccines or therapeutics. We show restriction of RVFV both by AMPK and its upstream activator LKB1, indicating an antiviral role for this signaling pathway. Furthermore, we found that AMPK is activated during RVFV infection, leading to the phosphorylation and inhibition of acetyl-CoA carboxylase, the first rate-limiting enzyme in fatty acid synthesis. Activating AMPK pharmacologically both restricted infection and reduced lipid levels. This restriction could be bypassed by treatment with the fatty acid palmitate, demonstrating that AMPK restricts RVFV infection through its inhibition of fatty acid biosynthesis. Lastly, we found that this pathway plays a broad role in antiviral defense since additional viruses from disparate families were also restricted by AMPK and LKB1. Therefore, AMPK is an important component of the cell intrinsic immune response that restricts infection through a novel mechanism involving the inhibition of fatty acid metabolism. PMID:22532801

Moser, Theresa S.; Schieffer, Daniel; Cherry, Sara

2012-01-01

372

p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells.  

PubMed

A diet high in fiber is associated with a decreased incidence and growth of colon cancers. Butyrate, a four-carbon short-chain fatty acid product of fiber fermentation within the colon, appears to mediate these salutary effects. We sought to determine the molecular mechanism by which butyrate mediates growth inhibition of colonic cancer cells and thereby to elucidate the molecular link between a high-fiber diet and the arrest of colon carcinogenesis. We show that concomitant with growth arrest, butyrate induces p21 mRNA expression in an immediate-early fashion, through transactivation of a promoter cis-element(s) located within 1.4 kb of the transcriptional start site, independent of p53 binding. Studies using the specific histone hyperacetylating agent, trichostatin A, and histone deacetylase 1 indicate that growth arrest and p21 induction occur through a mechanism involving histone hyperacetylation. We show the critical importance of p21 in butyrate-mediated growth arrest by first confirming that stable overexpression of the p21 gene is able to cause growth arrest in the human colon carcinoma cell line, HT-29. Furthermore, using p21-deleted HCT116 human colon carcinoma cells, we provide convincing evidence that p21 is required for growth arrest to occur in response to histone hyperacetylation, but not for serum starvation nor postconfluent growth. Thus, p21 appears to be a critical effector of butyrate-induced growth arrest in colonic cancer cells, and may be an important molecular link between a high-fiber diet and the prevention of colon carcinogenesis. PMID:9618491

Archer, S Y; Meng, S; Shei, A; Hodin, R A

1998-06-01

373

Inhibition of Microbial Growth by Ajoene, a Sulfur-Containing Compound Derived from Garlic  

Microsoft Academic Search

Ajoene, a garlic-derived sulfur-containing compound that prevents platelet aggregation, exhibited broad- spectrum antimicrobial activity. Growth of gram-positive bacteria, such as Bacillus cereus, Bacillus subtilis, Mycobacteriumsmegmatis,andStreptomycesgriseus,wasinhibitedat5 mgofajoeneperml.Staphylococcusaureus andLactobacillus plantarumalso were inhibited below 20 mg of ajoene per ml. For gram-negative bacteria, such asEscherichia coli,Klebsiella pneumoniae, andXanthomonas maltophilia, MICs were between 100 and 160 mg\\/ml. Ajoene also inhibited yeast growth at concentrations

RIE NAGANAWA; NAMI IWATA; KEIKO ISHIKAWA; HIROYUKI FUKUDA; TSUCHIYOSHI FUJINO; ANDATSUSHI SUZUKI

1996-01-01

374

Inhibition of mammalian and oncornavirus nucleic acid polymerase activities by alkoxybenzophenanthridine alkaloids.  

PubMed

The alkoxybenzophenanthridine alkaloids (coralyne acetosulfate, fagaronine chloride, and nitidine chloride) have been reported to possess antileukemic activity in mice. These compounds were tested for inhibition of reverse transcriptase activity of an RNA tumor virus and DNA polymerase, RNA polymerase, and polyadenylic acid polymerase activities of NIH-Swiss mouse embryos. Reverse transcriptase and DNA polymerase activities were strongly inhibited by these antileukemic alkaloids, whereas RNA polymerase and polyadenylic acid polymerase activities were only moderately affected. Viral and cellular DNA polymerase activities were potently diminished by the alkaloids when poly[d(A-T)], poly(dA)-oligo(dT), and poly(rA)-oligo(dT) template primers were used in the reaction mixture; however, no inhibition of enzyme activity was obtained with poly(rC)-oligo(dG) as template primer. These results suggest that alkoxybenzophenanthridine alkaloids inhibit DNA polymerase activity by interaction with A:T base pairs of the template primer. PMID:58719

Sethi, V S

1976-07-01

375

Lobaplatin inhibits growth of gastric cancer cells by inducing apoptosis  

PubMed Central

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

Yin, Chu-Yang; Lin, Xiao-Lin; Tian, Lei; Ye, Ming; Yang, Xin-Ying; Xiao, Xiu-Ying

2014-01-01

376

Androglobin knockdown inhibits growth of glioma cell lines  

PubMed Central

Globin family was famous for oxygen supply function of its members such as hemoglobin and myoglobin. With the progress of research, several members of this protein family have been proven to play roles in tumors including glioma. Androglobin (ADGB) is a recently identified member of globin family with very few studies about its function. In the present study, we show that ADGB plays an oncogene role in glioma. Lentiviral vector mediated ADGB knockdown inhibited the proliferation of glioma cell lines determined by MTT assay and colony formation assay. ADGB knockdown also increased the apoptosis of glioma cell line U251 assessed by flow cytometry. In addition, western blot showed that ADGB knockdown altered levels of several proteins related to proliferation, survival or apoptosis in U251 cells. These findings suggest ADGB is involved in the progression of glioma in vitro. PMID:24966926

Huang, Bo; Lu, Yi-Sheng; Li, Xia; Zhu, Zhi-Chuan; Li, Kui; Liu, Ji-Wei; Zheng, Jing; Hu, Ze-Lan

2014-01-01

377

Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2  

PubMed Central

Cholangiocarcinoma (CCA) is an often fatal primary malignancy of the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids (CBAs), which are correlated with bile duct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, the specific mechanisms by which bile acids may