Sample records for acids inhibit growth

  1. Calcite crystal growth rate inhibition by polycarboxylic acids

    USGS Publications Warehouse

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

    2001-01-01

    Calcite crystal growth rates measured in the presence of several polycarboxyclic acids show that tetrahydrofurantetracarboxylic acid (THFTCA) and cyclopentanetetracarboxylic acid (CPTCA) are effective growth rate inhibitors at low solution concentrations (0.01 to 1 mg/L). In contrast, linear polycarbocylic acids (citric acid and tricarballylic acid) had no inhibiting effect on calcite growth rates at concentrations up to 10 mg/L. Calcite crystal growth rate inhibition by cyclic polycarboxyclic acids appears to involve blockage of crystal growth sites on the mineral surface by several carboxylate groups. Growth morphology varied for growth in the absence and in the presence of both THFTCA and CPTCA. More effective growth rate reduction by CPTCA relative to THFTCA suggests that inhibitor carboxylate stereochemical orientation controls calcite surface interaction with carboxylate inhibitors. ?? 20O1 Academic Press.

  2. Glycyrrhizic acid inhibits influenza virus growth in embryonated eggs.

    PubMed

    Pompei, R; Paghi, L; Ingianni, A; Uccheddu, P

    1983-07-01

    Glycyrrhizic acid, at doses well tolerated by the cells in monolayer cultures, inhibited the recovery of hemagglutinins from both Influenza and Newcastle Disease virus-infected embryonated hen eggs. Since the drug had no effect on viral viability and did not impair the hemagglutinating activity of the virions, the growth of viruses into the embryo tissues might be mainly affected. Late viral replication steps, rather than the early ones, appeared to be involved in the inhibitory effect of glycyrrhizic acid. PMID:6633273

  3. The mechanism whereby growth hormone-release inhibiting hormone (somatostatin) inhibits food stimulated gastric acid secretion in the cat

    Microsoft Academic Search

    M. Albinus; E. L. Blair; E. R. Grund; J. D. Reed; D. J. Sanders; A. Gomez-Pan; A. V. Schally; G. M. Besser

    1975-01-01

    Growth hormone-release inhibiting hormone (somatostatin) inhibits the gastric acid response to food in concious cats. We have confirmed that this tetradecapeptide blocks the food stimulated gastrin release. However, the inhibition of gastrin release is delayed relative to that of acid secretion, showing that the inhibition of food stimulated acid secretion is by a primary effect on the acid secretory mechanism.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. Abscisic acid inhibits root growth in Arabidopsis through ethylene biosynthesis.

    PubMed

    Luo, Xingju; Chen, Zhizhong; Gao, Junping; Gong, Zhizhong

    2014-07-01

    When first discovered in 1963, abscisic acid (ABA) was called abscisin II because it promotes abscission. Later, researchers found that ABA accelerates abscission via ethylene. In Arabidopsis, previous studies have shown that high concentrations of ABA inhibit root growth through ethylene signaling but not ethylene production. In the present study in Arabidopsis, we found that ABA inhibits root growth by promoting ethylene biosynthesis. The ethylene biosynthesis inhibitor L-?-(2-aminoethoxyvinyl)-glycine reduces ABA inhibition of root growth, and multiple mutants of ACS (1-aminocyclopropane-1-carboxylate synthase) are more resistant to ABA in terms of root growth than the wild-type is. Two ABA-activated calcium-dependent protein kinases, CPK4 and CPK11, phosphorylate the C-terminus of ACS6 and increase the stability of ACS6 in ethylene biosynthesis. Plants expressing an ACS6 mutant that mimics the phosphorylated form of ACS6 produce more ethylene than the wild-type. Our results reveal an important mechanism by which ABA promotes ethylene production. This mechanism may be highly conserved among higher plants. PMID:24738778

  8. Muricholic Acids Inhibit Clostridium difficile Spore Germination and Growth

    PubMed Central

    Francis, Michael B.; Allen, Charlotte A.; Sorg, Joseph A.

    2013-01-01

    Infections caused by Clostridium difficile have increased steadily over the past several years. While studies on C. difficile virulence and physiology have been hindered, in the past, by lack of genetic approaches and suitable animal models, newly developed technologies and animal models allow these processes to be studied in detail. One such advance is the generation of a mouse-model of C. difficile infection. The development of this system is a major step forward in analyzing the genetic requirements for colonization and infection. While important, it is equally as important in understanding what differences exist between mice and humans. One of these differences is the natural bile acid composition. Bile acid-mediated spore germination is an important step in C. difficile colonization. Mice produce several different bile acids that are not found in humans. These muricholic acids have the potential to impact C. difficile spore germination. Here we find that the three muricholic acids (?-muricholic acid, ?-muricholic acid and ?-muricholic acid) inhibit C. difficile spore germination and can impact the growth of vegetative cells. These results highlight an important difference between humans and mice and may have an impact on C. difficile virulence in the mouse-model of C. difficile infection. PMID:24040011

  9. Recognition of specific patterns of amino acid inhibition of growth in higher plants, uncomplicated by glutamine-reversible `general amino acid inhibition'

    Microsoft Academic Search

    Carol A Bonner; Roy A Jensen

    1997-01-01

    The complexity of the regulatory mechanisms that govern amino acid biosynthesis, particularly in multibranched pathways, frequently results in sensitivity to growth inhibition by exogenous amino acids. Usually the inhibition caused by a given amino acid(s) is relieved by another amino acid(s), thus indicating the cause of inhibition to be a specific interference with endogenous formation of the latter amino acid(s).

  10. Liver acid sphingomyelinase inhibits growth of metastatic colon cancer

    PubMed Central

    Osawa, Yosuke; Suetsugu, Atsushi; Matsushima-Nishiwaki, Rie; Yasuda, Ichiro; Saibara, Toshiji; Moriwaki, Hisataka; Seishima, Mitsuru; Kozawa, Osamu

    2013-01-01

    Acid sphingomyelinase (ASM) regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate (S1P). These sphingolipids regulate carcinogenesis and proliferation, survival, and apoptosis of cancer cells. However, the role of ASM in host defense against liver metastasis remains unclear. In this study, the involvement of ASM in liver metastasis of colon cancer was examined using Asm–/– and Asm+/+ mice that were inoculated with SL4 colon cancer cells to produce metastatic liver tumors. Asm–/– mice demonstrated enhanced tumor growth and reduced macrophage accumulation in the tumor, accompanied by decreased numbers of hepatic myofibroblasts (hMFs), which express tissue inhibitor of metalloproteinase 1 (TIMP1), around the tumor margin. Tumor growth was increased by macrophage depletion or by Timp1 deficiency, but was decreased by hepatocyte-specific ASM overexpression, which was associated with increased S1P production. S1P stimulated macrophage migration and TIMP1 expression in hMFs in vitro. These findings indicate that ASM in the liver inhibits tumor growth through cytotoxic macrophage accumulation and TIMP1 production by hMFs in response to S1P. Targeting ASM may represent a new therapeutic strategy for treating liver metastasis of colon cancer. PMID:23298833

  11. Inhibition of Escherichia coli growth and diaminopimelic acid epimerase by 3-chlorodiaminopimelic acid.

    PubMed Central

    Baumann, R J; Bohme, E H; Wiseman, J S; Vaal, M; Nichols, J S

    1988-01-01

    The diaminopimelic acid (DAP) analog, 3-chloro-DAP, was synthesized and tested as the racemic acid for antibacterial activity and for inhibition of DAP epimerase. 3-Chloro-DAP was a potent inhibitor of DAP epimerase purified from Escherichia coli (Ki = 200 nM), and it is argued that 3-chloro-DAP is converted to a tight-binding transition state analog at the active site of this enzyme. Furthermore, 3-chloro-DAP inhibited growth of two E. coli mutants. In one of the mutants known for supersusceptibility to beta-lactams, inhibition was not seen until the mid-log phase of growth, while in the other mutant, a DAP auxotroph, inhibition occurred much earlier. Growth inhibition was reversed by DAP in both strains. In the auxotroph, the reversal was specific for meso-DAP, indicating that DAP epimerase was the target for 3-chloro-DAP. Thus we suggest a novel mechanism of bacterial growth inhibition which depends on DAP epimerase inhibition by a DAP analog. PMID:3056252

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

    PubMed

    Meguro, Ayano; Sato, Yutaka

    2014-01-01

    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. PMID:24686568

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

    NASA Astrophysics Data System (ADS)

    Meguro, Ayano; Sato, Yutaka

    2014-04-01

    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.

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

    PubMed Central

    2013-01-01

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

  15. Oleic acid inhibits stearic acid-induced inhibition of cell growth and pro-inflammatory responses in human aortic endothelial cells

    PubMed Central

    Harvey, Kevin A.; Walker, Candace L.; Xu, Zhidong; Whitley, Phillip; Pavlina, Thomas M.; Hise, Mary; Zaloga, Gary P.; Siddiqui, Rafat A.

    2010-01-01

    Saturated fatty acids (SFAs), significant components of both enteral/parenteral nutritional formulations (including diet), are linked to cardiovascular disease complications, such as atherosclerosis. We investigated whether oleic acid (C18:1n-9) reduces the growth inhibitory and pro-inflammatory effects of the stearic acid (C18:0) in human aortic endothelial cells (HAEC). Stearic acid induced growth inhibition at concentrations less than 50 ?M, whereas higher concentrations invoked cytotoxicity. Stearic acid-induced growth inhibition and cytotoxic effects were eradicated upon cosupplementation with oleic acid (25 ?M). Oleic acid (as low as 5 ?M) also inhibited the stearic acid-induced increase in intercellular adhesion molecule-1 (ICAM-1) expression. Stearic acid-induced phosphorylation of nuclear factor-kappa B (NF-?B), a transcriptional regulator of ICAM-1, was also reduced by oleic acid. HAECs supplemented with either stearic or oleic acid resulted in cellular incorporation of C18:0 and C18:1n-9, respectively. Stearic acid primarily incorporated into phospholipids without increasing the total fatty acid content in HAECs. In contrast, oleic acid, with or without stearic acid, incorporated into both phospholipids and triglycerides, with a significant increase in total fatty acid amounts in triglycerides. Our data suggest that oleic acid has the ability to reduce the inflammatory effects of long-chain SFAs in HAECs through reducing cellular stearic acid incorporation and NF-?B activation. PMID:20852092

  16. Auxin-Induced Ethylene Triggers Abscisic Acid Biosynthesis and Growth Inhibition1

    PubMed Central

    Hansen, Hauke; Grossmann, Klaus

    2000-01-01

    The growth-inhibiting effects of indole-3-acetic acid (IAA) at high concentration and the synthetic auxins 7-chloro-3-methyl-8-quinolinecarboxylic acid (quinmerac), 2-methoxy-3,6-dichlorobenzoic acid (dicamba), 4-amino-3,6,6-trichloropicolinic acid (picloram), and naphthalene acetic acid, were investigated in cleavers (Galium aparine). When plants were root treated with 0.5 mm IAA, shoot epinasty and inhibition of root and shoot growth developed during 24 h. Concomitantly, 1-aminocyclopropane-1-carboxylic acid (ACC) synthase activity, and ACC and ethylene production were transiently stimulated in the shoot tissue within 2 h, followed by increases in immunoreactive (+)-abscisic acid (ABA) and its precursor xanthoxal (xanthoxin) after 5 h. After 24 h of treatment, levels of xanthoxal and ABA were elevated up to 2- and 24-fold, relative to control, respectively. In plants treated with IAA, 7-chloro-3-methyl-8-quinolinecarboxylic acid, naphthalene acetic acid, 2-methoxy-3,6-dichlorobenzoic acid, and 4-amino-3,6,6-trichloropicolinic acid, levels of ethylene, ACC, and ABA increased in close correlation with inhibition of shoot growth. Aminoethoxyvinyl-glycine and cobalt ions, which inhibit ethylene synthesis, decreased ABA accumulation and growth inhibition, whereas the ethylene-releasing ethephon promoted ABA levels and growth inhibition. In accordance, tomato mutants defective in ethylene perception (never ripe) did not produce the xanthoxal and ABA increases and growth inhibition induced by auxins in wild-type plants. This suggests that auxin-stimulated ethylene triggers ABA accumulation and the consequent growth inhibition. Reduced catabolism most probably did not contribute to ABA increase, as indicated by immunoanalyses of ABA degradation and conjugation products in shoot tissue and by pulse experiments with [3H]-ABA in cell suspensions of G. aparine. In contrast, studies using inhibitors of ABA biosynthesis (fluridone, naproxen, and tungstate), ABA-deficient tomato mutants (notabilis, flacca, and sitiens), and quantification of xanthophylls indicate that ABA biosynthesis is influenced, probably through stimulated cleavage of xanthophylls to xanthoxal in shoot tissue. PMID:11080318

  17. Growth inhibition of Erwinia amylovora and related Erwinia species by neutralized short?chain fatty acids.

    PubMed

    Konecki, Katrin; Gernold, Marina; Wensing, Annette; Geider, Klaus

    2013-11-01

    Short-chain fatty acids (SCFAs) are used to preserve food and could be a tool for control of fire blight caused by Erwinia amylovora on apple, pear and related rosaceous plants. Neutralized acids were added to buffered growth media at 0.5–75 mM and tested at pHs ranging from 6.8 to 5.5. Particularly at low pH, SCFAs with a chain length exceeding that of acetic acid such as propionic acid were effective growth inhibitors of E. amylovora possibly due to uptake of free acid and its intracellular accumulation. We also observed high inhibition with monochloroacetic acid. An E. billingiae strain was as sensitive to the acids as E. amylovora or E. tasmaniensis. Fire blight symptoms on pear slices were reduced when the slices were pretreated with neutralized propionic acid. Propionic acid is well water soluble and could be applied in orchards as a control agent for fire blight. PMID:24077735

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

    NASA Astrophysics Data System (ADS)

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

    2000-01-01

    The crystallization of calcium carbonate minerals plays an integral role in the water chemistry of terrestrial ecosystems. Humic substances, which are ubiquitous in natural waters, have been shown to reduce or inhibit calcite crystal growth in experiments. The purpose of this study is to quantify and understand the kinetic effects of hydrophobic organic acids isolated from the Florida Everglades and a fulvic acid from Lake Fryxell, Antarctica, on the crystal growth of calcite (CaCO 3). Highly reproducible calcite growth experiments were performed in a sealed reactor at constant pH, temperature, supersaturation (? = 4.5), P CO2 (10 -3.5atm), and ionic strength (0.1 M) with various concentrations of organic acids. Higher plant-derived aquatic hydrophobic acids from the Everglades were more effective growth inhibitors than microbially derived fulvic acid from Lake Fryxell. Organic acid aromaticity correlated strongly with growth inhibition. Molecular weight and heteroatom content correlated well with growth inhibition, whereas carboxyl content and aliphatic nature did not.

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

    USGS Publications Warehouse

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

    2000-01-01

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

  20. Growth inhibition of plant pathogenic fungi by hydroxy fatty acids

    Microsoft Academic Search

    C T Hou; R J Forman III

    2000-01-01

      Hydroxy fatty acids are plant self-defense substances (Masui et al, Phytochemistry1989). Three types of hydroxy fatty acids: 10-hydroxystearic acid (HSA), 7S,10S-dihydroxy-8(E)-octadecenoic acid (DOD), and 12,13,17-trihydroxy-9(Z)-octadecenoic acid (THOA) were tested against the following plant pathogenic fungi: Erysiphe graminis f sp tritici (common disease name, wheat powdery mildew); Puccinia recondita (wheat leaf rust); Pseudocercosporella herpotrichoides (wheat foot rot); Septoria nodorum (wheat glume

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

    PubMed Central

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

    2012-01-01

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

  2. Protection by selective amino acid solutions against doxorubicin induced growth inhibition of Escherichia coli

    Microsoft Academic Search

    Huda S. Amash; Olen R. Brown; Victor A. Padron

    1995-01-01

    1.1. Incubation of Escherichia coli with 0.7 mM doxorubicin in MBS-glucose medium resulted in complete growth inhibition, an inhibition that was blocked by placing specific amino acids (AA) in the medium.2.2. The mechanism of protection by AA was similar to that reported previously for cells poisoned by hyperoxia and by paraquat, e.g. of 20 common AA, ten protect, ten do

  3. Quantitative Analysis of the Modes of Growth Inhibition by Weak Organic Acids in Saccharomyces cerevisiae

    PubMed Central

    Ullah, Azmat; Orij, Rick; Brul, Stanley

    2012-01-01

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

  4. [Chemical structure of dicarboxylic acids and their capacity inhibiting of calcium oxalate crystal growth].

    PubMed

    Deng, Sui-ping; Hu, Peng; Ouyang, Jian-ming

    2007-10-01

    The effect of dicarboxylic acids with a three C-C bonds distance on the crystallization of calcium oxalate (CaOxa) was investigated in silica gel system by means of X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). These acids include succinic acid, maleic acid, fumaric acid, malic acid, L-aspartic acid and tartaric acid. All the dicarboxylic acids can inhibit the aggregation of calcium oxalate monohydrate (COM) and induce the formation of calcium oxalate dehydrate (COD). But their ability to inhibit the growth and aggregation of COM, to diminish the specific surface area of COM and to induce COD formation were strengthened as the number of the substituted hydroxyl or amino group increased. The molecular mechanisms were discussed in terms of chemical structures of dicarboxylic acids. Only the dicarboxylic acids with a HOOC-CH(R)-CH2-COOH (R=OH or NH2) group were found to have the best inhibitory effect on the CaOxa urinary stones. The results could provide some clue to looking for new drugs for urinary stones in clinic. PMID:18306777

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

    PubMed

    Chipley, J R; Uraih, N

    1980-08-01

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

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

    Microsoft Academic Search

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

    1985-01-01

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

  7. Growth Stimulation and Inhibition Effects of 4-Hydroxybenzoic Acid and Some Related Compounds on the Freshwater Green Alga Pseudokirchneriella subcapitata

    Microsoft Academic Search

    Y. Kamaya; S. Tsuboi; T. Takada; K. Suzuki

    2006-01-01

    4-Hydroxybenzoic acid (4-HBA) exhibited low algal toxicity with the 72-h median inhibition concentration (IC50) of 9.9 mmol\\/L in the standard growth inhibition test using the freshwater green alga Pseudokirchneriella subcapitata. In contrast, it stimulated the algal growth at lower concentrations ranging from 0.1 to 1.0 mmol\\/L. Comparative studies\\u000a with benzoic acid and 2- and 3-hydroxybenzoic acids (2-HBA and 3-HBA) indicated

  8. Competitive Inhibition of Amino Acid Uptake Suppresses Chlamydial Growth: Involvement of the Chlamydial Amino Acid Transporter BrnQ? †

    PubMed Central

    Braun, Peter R.; Al-Younes, Hesham; Gussmann, Joscha; Klein, Jeannette; Schneider, Erwin; Meyer, Thomas F.

    2008-01-01

    Chlamydiaceae are obligate intracellular bacterial pathogens that strictly depend on host metabolites, such as nucleotides, lipids, and amino acids. Depletion of amino acids in cell culture media results in abnormal chlamydial development in vitro. Surprisingly, enrichment of certain amino acids also retards chlamydial growth. Our experiments revealed that the antichlamydial effects are largely independent of changes in the host cell transcriptome or proteome and in the major signal transduction pathway modulated by amino acids, the mTOR (mammalian target of rapamycin) pathway. Furthermore, the chlamydial growth inhibition induced by leucine, isoleucine, methionine, or phenylalanine was completely reversed by concomitant addition of valine. In contrast, the growth inhibition induced by serine, glycine, or threonine was not reversed by valine addition. Functional characterization of the only predicted chlamydial transporter for branched-chain amino acids, BrnQ, revealed that it can be blocked by leucine, isoleucine, methionine, or phenylalanine but not by serine, glycine, or threonine. This chlamydial transporter is the only known BrnQ homolog possessing specificity for methionine, suggesting a unique strategy for methionine uptake among gram-negative bacteria. The antichlamydial effects of leucine, isoleucine, methionine, and phenylalanine could be explained as competitive inhibition of the BrnQ transporter and subsequent valine starvation. PMID:18024516

  9. Pathogen survival during anaerobic digestion: Fatty acids inhibit anaerobic growth of Escherichia coli

    Microsoft Academic Search

    Pirshing Abdul; David Lloyd

    1985-01-01

    Summary The fate of pathogens in anaerobic digesters has been studied in a laboratory model system in which glucose-nutrient broth cultures of genetically-defined strains ofEscherichia coli received additions of fatty acids at concentrations similar to those attained during anaerobic treatment of farm wastes. Marked concentration-dependent inhibition of growth was observed for both antibiotic resistant and sensitive strains, and the effects

  10. Selective growth inhibition of human malignant melanoma cells by syringic acid-derived proteasome inhibitors

    PubMed Central

    2013-01-01

    Background It has been shown that proteasome inhibition leads to growth arrest in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was found that some of these inhibitors do not induce apoptosis in several human normal cell lines. This selective activity makes proteasome inhibition a promising target for new generation of anticancer drugs. Clinical validation of the proteasome, as a therapeutic target in oncology, has been provided by the dipeptide boronic acid derivative; bortezomib. Bortezomib has proven to be effective as a single agent in multiple myeloma and some forms of non-Hodgkin’s lymphoma. Syringic acid (4-hydroxy-3,5-dimethoxybenzoic acid, 1), a known phenolic acid, was isolated from the methanol extract of Tamarix aucheriana and was shown to possess proteasome inhibitory activity. Methods Using Surflex-Dock program interfaced with SYBYL, the docking affinities of syringic acid and its proposed derivatives to 20S proteasome were studied. Several derivatives were virtually proposed, however, five derivatives: benzyl 4-hydroxy-3,5-dimethoxybenzoate (2), benzyl 4-(benzyloxy)-3,5-dimethoxybenzoate (3), 3'-methoxybenzyl 3,5-dimethoxy-4-(3'-methoxybenzyloxy)benzoate (4), 3'-methoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (5) and 3',5'-dimethoxybenzyl 4-hydroxy-3,5-dimethoxybenzoate (6), were selected based on high docking scores, synthesized, and tested for their anti-mitogenic activity against human colorectal, breast and malignant melanoma cells as well as normal human fibroblast cells. Results Derivatives 2, 5, and 6 showed selective dose-dependent anti-mitogenic effect against human malignant melanoma cell lines HTB66 and HTB68 with minimal cytotoxicity on colorectal and breast cancer cells as well as normal human fibroblast cells. Derivatives 2, 5 and 6 significantly (p???0.0001) inhibited the various proteasomal chymotrypsin, PGPH, and trypsin like activities. They growth arrested the growth of HTB66 cells at G1 and G2-phases. They also arrested the growth of HTB68 cells at S- and G2-phase, respectively. Moreover, derivatives 2, 5, and 6 markedly induced apoptosis (? 90%) in both HTB66 and HTB68. Conclusions Computer-derived syringic acid derivatives possess selective anti-mitogenic activity on human malignant melanoma cells that may be attributed to perturbation of cell cycle, induction of apoptosis and inhibition of various 26S proteasomal activities. PMID:23958424

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

    PubMed Central

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

    2010-01-01

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

  12. Ethylene Formation in Pea Seedlings; Its Relation to the Inhibition of Bud Growth Caused by Indole-3-Acetic Acid 1

    PubMed Central

    Burg, Stanley P.; Burg, Ellen A.

    1968-01-01

    Indole-3-acetic acid stimulates ethylene production in the nodal region of pea stems, and the gas inhibits bud growth. At all concentrations of IAA there is a close correlation between the intensity and duration of ethylene production and the bud inhibition which results. Kinetin reverses the inhibitory actions of ethylene and IAA on bud growth. It is concluded that auxins suppress bud development by stimulating ethylene formation. The possibility that auxin induced ethylene formation controls apical dominance is considered. PMID:16656884

  13. Docosahexaenoic acid (DHA), a primary tumor suppressive omega-3 fatty acid, inhibits growth of colorectal cancer independent of p53 mutational status.

    PubMed

    Kato, Taeko; Kolenic, Nicole; Pardini, Ronald S

    2007-01-01

    Human colon carcinoma COLO 205, carrying wild type p53, grown subcutaneously in athymic mice was inhibited 80% by a high fat menhaden oil diet containing a mixture of omega-3 fatty acids compared to the low fat corn oil diet containing omega-6 fatty acids. Feeding a high fat diet of golden algae oil containing docosahexaenoic acid (DHA) as the sole long chain omega-3 fatty acid resulted in 93% growth inhibition. Similar findings were previously reported for WiDr colon carcinoma containing mutated p53 (His237). In vitro, 125 muM DHA inhibited COLO 205 growth by 81%, WiDr by 42%, while eicosapentaenoic acid (EPA) marginally inhibited growth of both lines by approximately 30%. DHA inhibited cell proliferation by 41% in WiDr but did not significantly inhibit proliferation in COLO 205. Cell cycle analysis revealed that DHA arrested cell cycle at Resting/Gap 1 (G0/G1 phase) in WiDr and at Gap 2/Mitosis (G2/M) phase in COLO 205. DHA induced apoptosis in COLO 205 but not in WiDr, and EPA did not induce apoptosis in either line. Taken together, these findings suggest DHA is the primary tumor suppressive omega-3 fatty acid in vivo and in vitro and inhibits cancer growth by p53 dependent and independent pathways, while the marginal inhibition by EPA is p53 independent. PMID:17640164

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

    USGS Publications Warehouse

    Reddy, Michael M.; Leenheer, Jerry

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    USGS Publications Warehouse

    Reddy, Michael M.

    2012-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

    Reddy, Michael M.

    2012-08-01

    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.

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

    PubMed

    Meinelt, Thomas; Phan, Thy-My; Behrens, Sascha; Wienke, Andreas; Pedersen, Lars-Flemming; Liu, Dibo; Straus, David L

    2015-04-01

    Peracetic acid (PAA) is a therapeutic agent used for disinfection in aquaculture, but it must be investigated thoroughly in order to mitigate diseases without harming the fish. Successful disinfectants (like PAA) should not leave dangerous residues in the environment in order to successfully contribute to sustainable aquaculture. The aim of our study was to compare the effectiveness of 6 commercial PAA products with different molecular PAA:H2O2 ratios to reduce bacterial growth of Aeromonas salmonicida and Yersinia ruckeri and to determine effective concentrations and exposure times. All products reduced colony-forming units (CFUs) of A. salmonicida and Y. ruckeri. Products with higher molecular PAA:H2O2 ratios inhibited growth better than products with lower molecular PAA:H2O2 ratios at the same PAA concentration; this indicates that H2O2 is not the driving force in the reduction of A. salmonicida and Y. ruckeri growth by PAA in vitro. The practical application of the products with high molecular PAA:H2O2 ratios should be prioritized if these pathogens are diagnosed. PMID:25850398

  19. 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...

  20. Mechanism of Growth Inhibition by Free Bile Acids in Lactobacilli and Bifidobacteria

    Microsoft Academic Search

    Peter Kurdi; Koji Kawanishi; Kanako Mizutani; Atsushi Yokota

    2006-01-01

    The effects of the free bile acids (FBAs) cholic acid (CA), deoxycholic acid (DCA), and chenodeoxycholic acid on the bioenergetics and growth of lactobacilli and bifidobacteria were investigated. It was found that these FBAs reduced the internal pH levels of these bacteria with rapid and stepwise kinetics and, at certain concentrations, dissipated pH. The bile acid concentrations that dissipated pH

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    Microsoft Academic Search

    Liam Good; Peter E. Nielsen

    1998-01-01

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

  4. Inhibition of Abscisic Acid Biosynthesis in Cercospora rosicola by Inhibitors of Gibberellin Biosynthesis and Plant Growth Retardants

    PubMed Central

    Norman, Shirley M.; Poling, Stephen M.; Maier, Vincent P.; Orme, Edward D.

    1983-01-01

    The fungus Cercospora rosicola produces abscisic acid (ABA) as a secondary metabolite. We developed a convenient system using this fungus to determine the effects of compounds on the biosynthesis of ABA. Inasmuch as ABA and the gibberellins (GAs) both arise via the isoprenoid pathway, it was of interest to determine if inhibitors of GA biosynthesis affect ABA biosynthesis. All five putative inhibitors of GA biosynthesis tested inhibited ABA biosynthesis. Several plant growth retardants with poorly understood actions in plants were also tested; of these, six inhibited ABA biosynthesis to varying degrees and two had no effect. Effects of plant growth retardants on various branches of the isoprenoid biosynthetic pathway may help to explain some of the diverse and unexpected results reported for these compounds. Knowledge that certain inhibitors of GA biosynthesis also have the ability to inhibit ABA biosynthesis in C. rosicola indicates the need for further studies in plants on the mode of action of these compounds. PMID:16662775

  5. Triterpene acids from apple peel inhibit lepidopteran larval midgut lipases and larval growth.

    PubMed

    Christeller, John T; McGhie, Tony K; Poulton, Joanne; Markwick, Ngaire P

    2014-07-01

    Fruit extracts from apple, kiwifruit, feijoa, boysenberry, and blueberry were screened for the presence of lipase inhibitory compounds against lepidopteran larval midgut crude extracts. From 120 extracts, six showed significant inhibition with an extract from the peel of Malus × domestica cv. "Big Red" showing highest levels of inhibition. Because this sample was the only apple peel sample in the initial screen, a survey of peels from seven apple cultivars was undertaken and showed that, despite considerable variation, all had inhibitory activity. Successive solvent fractionation and LC-MS of cv. "Big Red" apple peel extract identified triterpene acids as the most important inhibitory compounds, of which ursolic acid and oleanolic acid were the major components and oxo- and hydroxyl-triterpene acids were minor components. When ursolic acid was incorporated into artificial diet and fed to Epiphyas postvittana Walker (Tortricidae: Lepidoptera) larvae at 0.16% w/v, a significant decrease in larval weight was observed after 21 days. This concentration of ursolic acid is less than half the concentration reported in the skin of some apple cultivars. PMID:24753088

  6. Retinoic acid inhibits the infectivity and growth of Chlamydia pneumoniae in epithelial and endothelial cells through different receptors.

    PubMed

    Puolakkainen, Mirja; Lee, Amy; Nosaka, Tadayoshi; Fukushi, Hideto; Kuo, Cho-Chou; Campbell, Lee Ann

    2008-05-01

    Chlamydia pneumoniae is a human respiratory pathogen that has also been associated with cardiovascular disease. C. pneumoniae infection accelerates atherosclerotic plaque development in hyperlipidemic animals and promotes oxidation of low density lipoprotein in vitro. All-trans-retinoic acid (ATRA), an antioxidant, has been shown to inhibit C. pneumoniae infectivity for endothelial cells by preventing binding of the organism to the M6P/IGF2 receptor on the cell surface. This current study investigates whether ATRA similarly affects C. pneumoniae infectivity of epithelial cells, which are the primary site of infection in the respiratory tract, and the effects on intracellular growth in both endothelial and epithelial cells. Because ATRA binds to both the nuclear retinoid acid receptor (RAR) and the M6P/IGF2 receptor, 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB), an ATRA analog, which binds to the RAR but not the M6P/IGF2 receptor was used to differentiate the receptor mediating the effects of ATRA. The results of this study showed two separate effects of ATRA. The first effect is through interaction with the M6P/IGF2 receptor on the cell surface preventing attachment of the organism (inhibition by ATRA but not TTNPB) in endothelial cells and the second is through the nuclear receptor (inhibition by both ATRA and TTNPB) which inhibits growth in both epithelial and endothelial cells. PMID:18162363

  7. Growth inhibition of lactic acid bacteria in ham by nisin: a model approach.

    PubMed

    Kalschne, Daneysa L; Geitenes, Simone; Veit, Marilei R; Sarmento, Cleonice M P; Colla, Eliane

    2014-12-01

    Lactic acid bacteria (LAB) have been described as spoilage organisms in vacuum-packed cooked ham. A Fractional Factorial Design was performed to investigate the relative merits of sodium chloride, sodium lactate, sodium tripolyphosphate, sodium erythorbate, nisin and pediocin, in limiting the Lactobacillus sakei growth in broth culture. This allowed rejection of sodium chloride, sodium lactate and sodium erythorbate (no significant effects on growth), and a Central Composite Rotatable Design broth culture study was performed comparing the effects of nisin and pediocin. From this study, nisin was identified as a more important variable for inclusion into a cooked ham model (significant effects on growth parameters: logarithmic increase in the population, exponential microbial growth rate and lag phase extension). The validation of this outcome in a model formulation of vacuum-packed sliced cooked ham (0.001%, 0.007% and 0.013% of nisin) stored for 60days, confirmed the inhibitory effect of nisin on total LAB growth. PMID:25108514

  8. Targeting Mitochondrial STAT3 with the Novel Phospho-Valproic Acid (MDC-1112) Inhibits Pancreatic Cancer Growth in Mice

    PubMed Central

    Mackenzie, Gerardo G.; Huang, Liqun; Alston, Ninche; Ouyang, Nengtai; Vrankova, Kvetoslava; Mattheolabakis, George; Constantinides, Panayiotis P.; Rigas, Basil

    2013-01-01

    New agents are needed to treat pancreatic cancer, one of the most lethal human malignancies. We synthesized phospho-valproic acid, a novel valproic acid derivative, (P-V; MDC-1112) and evaluated its efficacy in the control of pancreatic cancer. P-V inhibited the growth of human pancreatic cancer xenografts in mice by 60%–97%, and 100% when combined with cimetidine. The dominant molecular target of P-V was STAT3. P-V inhibited the phosphorylation of JAK2 and Src, and the Hsp90-STAT3 association, suppressing the activating phosphorylation of STAT3, which in turn reduced the expression of STAT3-dependent proteins Bcl-xL, Mcl-1 and survivin. P-V also reduced STAT3 levels in the mitochondria by preventing its translocation from the cytosol, and enhanced the mitochondrial levels of reactive oxygen species, which triggered apoptosis. Inhibition of mitochondrial STAT3 by P-V was required for its anticancer effect; mitochondrial STAT3 overexpression rescued animals from the tumor growth inhibition by P-V. Our results indicate that P-V is a promising candidate drug against pancreatic cancer and establish mitochondrial STAT3 as its key molecular target. PMID:23650499

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

    PubMed

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

    2013-09-01

    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

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

    Microsoft Academic Search

    Donald W. Sparling

    1990-01-01

    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

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

    PubMed Central

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

    1997-01-01

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

  12. Effect of Inhibition of Deoxyribonucleic Acid and Protein Synthesis on the Direction of Cell Wall Growth in Streptococcus faecalis

    PubMed Central

    Higgins, M. L.; Daneo-Moore, L.; Boothby, D.; Shockman, G. D.

    1974-01-01

    Selective inhibition of protein synthesis in Streptococcus faecalis (ATCC 9790) was accompanied by a rapid and severe inhibition of cell division and a reduction of enlargement of cellular surface area. Continued synthesis of cell wall polymers resulted in rapid thickening of the wall to an extent not seen in exponential-phase populations. Thus, the normal direction of wall growth was changed from a preferential feeding out of new wall surface to that of thickening existing cell surfaces. However, the overall manner in which the wall thickened, from nascent septa toward polar regions, was the same in both exponential-phase and inhibited populations. In contrast, selective inhibition of deoxyribonucleic acid (DNA) synthesis using mitomycin C was accompanied by an increase in cellular surface area and by division of about 80% of the cells in random populations. Little or no wall thickening was observed until the synthesis of macromolecules other than DNA was impaired and further cell division ceased. Concomitant inhibition of both DNA and protein synthesis inhibited cell division but permitted an increase in average cell volume. In such doubly inhibited cells, walls thickened less than in cells inhibited for protein synthesis only. On the basis of the results obtained, a model for cell surface enlargement and cell division is presented. The model proposes that: (i) each wall enlargement site is influenced by an individual chromosome replication cycle; (ii) during chromosome replication peripheral surface enlargement would be favored over thickening (or septation); (iii) a signal associated with chromosome termination would favor thickening (and septation) at the expense of surface enlargement; and (iv) a factor or signal related to protein synthesis would be required for one or more of the near terminal stages of cell division or cell separation, or both. Images PMID:4133352

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

    PubMed

    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

    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

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

    SciTech Connect

    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

    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.

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

    PubMed Central

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

    2012-01-01

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

  16. Kinetic analysis on the production of polyhydroxyalkanoates from volatile fatty acids by Cupriavidus necator with a consideration of substrate inhibition, cell growth, maintenance, and product formation

    Microsoft Academic Search

    Jin Wang; Zheng-Bo Yue; Guo-Ping Sheng; Han-Qing Yu

    2010-01-01

    Volatile fatty acids (VFAs) could be utilized by Cupriavidus necator (previously named as Ralstonia eutropha) as its sole carbon and energy source for growth and polyhydroxyalkanoates (PHAs) synthesis. In such a biosynthesis, VFAs at a high concentration had an inhibition on cell growth and deteriorate metabolite production. In this work the kinetics of PHAs production and consumption of VFAs by

  17. Release of cyclic phosphatidic acid from gelatin-based hydrogels inhibit colon cancer cell growth and migration.

    PubMed

    Tsukahara, Tamotsu; Murakami-Murofushi, Kimiko

    2012-01-01

    Microparticle and nanoparticle formulations are widely used to improve the bioavailability of low-solubility drugs and as vehicles for organ- and tissue-specific targeted drug delivery. We investigated the effect of a novel, controlled-release form of a bioactive lipid, cyclic phosphatidic acid (cPA), on human colon cancer cell line functions. We encapsulated cPA in gelatin-based hydrogels and examined its ability to inhibit the viability and migration of HT-29 and DLD-1 cells in vitro and the LPA-induced activity of the transcription factor peroxisome proliferator-activated receptor gamma (PPAR?). The hydrogel delivery system prolonged cPA release into the culture medium. Accordingly, cPA-hydrogel microspheres substantially inhibited LPA-induced PPAR? activity and cell growth and migration compared with that of cells cultured with cPA alone. Thus, hydrogel microspheres are a potential system for stable and efficient delivery of bioactive lipids such as cPA and may offer a new strategy for targeted colon cancer treatment. PMID:23008752

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

    PubMed Central

    Srivastava, Sanjay K.

    2013-01-01

    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

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

    PubMed

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

    2014-10-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    SciTech Connect

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

    2013-01-01

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

  2. RAR?2-Mediated Growth Inhibition in HeLa Cells

    Microsoft Academic Search

    Seong Pan Si; Xinhua Lee; Hui C. Tsou; Rachel Buchsbaum; Elmi Tibaduiza; Monica Peacocke

    1996-01-01

    Retinoic acid inhibits the growth of a variety of normal and transformed cellsin vitroandin vivo.How retinoic acid inhibits cell growth is poorly understood but involves interactions between the ligand and a series of nuclear and cytoplasmic receptors. The nuclear receptors for retinoic acid are of two types, the RARs and the RXRs. Each can function as a ligand-inducible transcription enhancing

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-04-01

    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

  5. Ethylene-induced inhibition of root growth requires abscisic acid function in rice (Oryza sativa L.) seedlings.

    PubMed

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

    2014-10-01

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

  6. Methaneseleninic acid and ?-Tocopherol combination inhibits prostate tumor growth in Vivo in a xenograft mouse model

    PubMed Central

    Singh, Chandra K.; Ndiaye, Mary A.; Siddiqui, Imtiaz A.; Nihal, Minakshi; Havighurst, Thomas; Kim, KyungMann; Zhong, Weixiong; Mukhtar, Hasan; Ahmad, Nihal

    2014-01-01

    Studies have shown that vitamin E and selenium possess antiproliferative effects against prostate cancer (PCa). However, results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) suggest that vitamin E (?-tocopheryl acetate; 400 mg) and/or selenium (L-selenomethionine; 200 ?g) were ineffective against PCa in humans. It is arguable that the selected dose/formulation of vitamin E/selenium were not optimal in SELECT. Thus, additional studies are needed to define the appropriate formulations/dose regimens of these agents. Here, we investigated the effect of methaneseleninic acid (MSA; 41 ?g/kg) and/or ?-tocopherol (?T; 20.8 mg/kg or 41.7 mg/kg) in Nu/J mice implanted with 22R?1 tumors. MSA (41 ?g/kg) and ?T (20.8 mg/kg) combination was most consistent in imparting anti-proliferative response; resulting in a significant decrease in i) tumor volume/weight, ii) serum PSA, and iii) Ki-67 immunostaining. Further, we observed i) an upregulation of pro-apoptosis Bax and a down-regulation of the pro-survival Bcl2, and ii) an increase in pro-apoptosis Bad. Furthermore, the combination resulted in a modulation of apolipoprotein E, selenoprotein P and Nrf2 in a fashion that favors antiproliferative responses. Overall, our study suggested that a combination of MSA and ?T, at lower dose regimen, could be useful in PCa management. PMID:25004451

  7. Methaneseleninic acid and ?-Tocopherol combination inhibits prostate tumor growth in Vivo in a xenograft mouse model.

    PubMed

    Singh, Chandra K; Ndiaye, Mary A; Siddiqui, Imtiaz A; Nihal, Minakshi; Havighurst, Thomas; Kim, KyungMann; Zhong, Weixiong; Mukhtar, Hasan; Ahmad, Nihal

    2014-06-15

    Studies have shown that vitamin E and selenium possess antiproliferative effects against prostate cancer (PCa). However, results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) suggest that vitamin E (?-tocopheryl acetate; 400 mg) and/or selenium (L-selenomethionine; 200 ?g) were ineffective against PCa in humans. It is arguable that the selected dose/formulation of vitamin E/selenium were not optimal in SELECT. Thus, additional studies are needed to define the appropriate formulations/dose regimens of these agents. Here, we investigated the effect of methaneseleninic acid (MSA; 41 µg/kg) and/or ?-tocopherol (?T; 20.8 mg/kg or 41.7 mg/kg) in Nu/J mice implanted with 22R?1 tumors. MSA (41 µg/kg) and ?T (20.8 mg/kg) combination was most consistent in imparting anti-proliferative response; resulting in a significant decrease in i) tumor volume/weight, ii) serum PSA, and iii) Ki-67 immunostaining. Further, we observed i) an upregulation of pro-apoptosis Bax and a down-regulation of the pro-survival Bcl2, and ii) an increase in pro-apoptosis Bad. Furthermore, the combination resulted in a modulation of apolipoprotein E, selenoprotein P and Nrf2 in a fashion that favors antiproliferative responses. Overall, our study suggested that a combination of MSA and ?T, at lower dose regimen, could be useful in PCa management. PMID:25004451

  8. Basal and acidic fibroblast growth factor-induced atrial natriuretic peptide gene expression and secretion is inhibited by staurosporine.

    PubMed

    Tokola, H; Salo, K; Vuolteenaho, O; Ruskoaho, H

    1994-04-15

    We examined the mechanisms involved in the activation of atrial natriuretic peptide (ANP) gene expression and secretion in response to acidic fibroblast growth factor (aFGF) by studying the effects of staurosporine, a protein kinase C inhibitor, and 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of protein kinase C, on basal and AFGF-induced ANP messenger RNA (mRNA) and immunoreactive ANP (IR-ANP) levels in cultured neonatal rat cardiac myocytes. Acidic FGF caused a dose- and time-dependent increase in IR-ANP and immunoreactive N-terminal fragment of proANP (IR-NT-proANP) release into the culture medium from ventricular but not from atrial myocytes. In ventricular cells, 50 ng/ml aFGF for 24 or 48 h resulted in a 70% or 181% increase, respectively, in the accumulation of IR-ANP into the culture medium. Acidic FGF also stimulated ANP gene expression significantly; after 48 h of incubation, the ANP mRNA levels of aFGF-treated ventricular myocytes were 205% (P < 0.001) higher than those of control cells. Staurosporine alone at concentration of 10 nM significantly decreased the basal IR-ANP and IR-NT-proANP secretion, and inhibited the aFGF-induced increase in ANP mRNA and IR-ANP levels in ventricular myocytes. TPA (100 nM) alone significantly stimulated ANP gene expression and secretion but these effects were not augmented by combining aFGF with TPA. High performance liquid chromatographical analysis showed that atrial and ventricular myocytes maintained in serum-free medium were capable of secreting processed, ANP99-126 sized material, and that aFGF did not alter the processing of ANP in ventricular cultures. These results demonstrate that aFGF is a potent stimulator of ANP gene expression and secretion in cultured neonatal rat ventricular but not in atrial cells. The observations that (a) staurosporine completely abolished the effects of aFGF on ANP gene expression and release and (b) ANP secretory and gene expression inducing effects of phorbol ester were not augmented by aFGF, suggest an important role of protein kinase C in mediating aFGF-induced ANP gene expression and secretion. PMID:7519562

  9. Efficacy of washing meat surfaces with 2% levulinic, acetic, or lactic acid for pathogen decontamination and residual growth inhibition.

    PubMed

    Carpenter, C E; Smith, J V; Broadbent, J R

    2011-06-01

    We compared spray washing at 55.4 °C with 2% levulinic acid to that with lactic or acetic acid for decontamination of pathogenic bacteria inoculated onto meat surfaces, and their residual protection against later growth of pathogenic bacteria. The model systems included Escherichia coli O157:H7 on beef plate, Salmonella on chicken skin and pork belly, and Listeria monocytogenes on turkey roll. In the decontamination studies, acid washes lowered recoverable numbers of pathogens by 0.6 to 1 log/cm(2) as compared to no-wash controls, and only lactic acid lowered the number of pathogens recovered as compared to the water wash. Washing with levulinic acid at 68.3 or 76.7 °C did not result in additional decontamination of E. coli. Acetic acid prevented residual growth of E. coli and L. monocytogenes, and it reduced numbers of Salmonella on chicken skin to below recoverable levels. Overall, levulinic acid did not provide as effective decontamination as lactic acid nor residual protection as acetic acid. PMID:21251765

  10. Inhibition of enterotoxin production by, and growth of enteropathogens in a lactic acid-fermenting cereal gruel

    Microsoft Academic Search

    R. R. Kingamkono; E. Sjögren; U. Svanberg

    1998-01-01

    Growth and enterotoxin production of three strains of Campylobacter jejuni or Escherichia coli known to produce heat labile enterotoxins were evaluated when added into a lactic acid-fermenting cereal gruel, togwa. A single strain of each of the enteropathogens was simultaneously inoculated with a lactic acid starter culture (sc) to reach a level of about 107 c.f.u.\\/ml and was left to

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

    PubMed

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

    2015-04-01

    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

  12. ???????????????????????????????????????????????????????????????? Escherichia coli ????????????????????????? ISOLATION AND SCREENING OF LACTIC ACID BACTERIA CAPABLE OF INHIBITING GROWTH OF SOME ESCHERICHIA COLI ISOLATED FROM SWINE

    Microsoft Academic Search

    Mongkhon Punyarat; Narumol Thongwai

    One hundred and forty-seven strains of lactic acid bacteria (LAB) were isolated from some soils, fermented foods, vegetables, fruits, milk and animal products. After cultivation in MRS broth at 37 ?C for 96 hours, each culture supernatant was evaluated its growth inhibitory activity by using a paper disc diffusion method against one strain of Escherichia coli O157:H7 and nine strains

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

    SciTech Connect

    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

    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.

  14. Anaerobic lactic acid degradation during ensilage of whole crop maize inoculated with lactobacillus buchneri inhibits yeast growth and improves aerobic stability

    PubMed

    Driehuis; Elferink; Spoelstra

    1999-10-01

    Aerobic deterioration of silages is initiated by (facultative) aerobic micro-organisms, usually yeasts, that oxidize the preserving organic acids. In this study, a Lactobacillus buchneri strain isolated from maize silage was evaluated for its potential as a bacterial inoculant that enhances aerobic stability of silages. In four experiments, chopped whole crop maize (30-43% dry matter (DM)) was inoculated with Lact. buchneri and ensiled in laboratory silos. Uninoculated silages served as controls. Analysis of silages treated with Lact. buchneri at levels of 103-106 cfu g-1 after about 3 months of anaerobic storage showedthat acetic acid and 1-propanol contents increased with inoculum levels above 104 cfu g-1,whereas lactic acid decreased. Propionic acid, silage pH and DM loss increased withinoculum levels above 105 cfu g-1. Time course experiments with maize inoculated with Lact. buchneri at 4 x 104-2 x 105 cfu g-1 showed that up to 7-14 d after ensiling, Lact. buchneri had no effect on silage characteristics. Thereafter, the lactic acid content of the inoculated silages declined and, simultaneously, acetic acid and, to a lesser extent, propionic acid and 1-propanol, accumulated. Inoculation reduced survival of yeasts during the anaerobic storage phase and inhibited yeast growth when the silage was exposed to O2, resulting in a substantial improvement in aerobic stability. The results indicate that the use of Lact. buchneri as a silage inoculant can enhance aerobic stability by inhibition of yeasts. The ability of the organism to ferment lactic acid to acetic acid appears to be an important underlying principle of this effect. PMID:10583687

  15. Vitamin E analog alpha-TEA, methylseleninic acid, and trans-resveratrol in combination synergistically inhibit human breast cancer cell growth.

    PubMed

    Snyder, Rachel M; Yu, Weiping; Jia, Li; Sanders, Bob G; Kline, Kimberly

    2008-01-01

    Alpha-tocopherol ether-linked acetic acid analog [2,5,7,8-tetramethyl-2R-(4R, 8R-12-trimethyltridecyl) chroman-6-yloxyacetic acid (alpha-TEA)] is a novel form of vitamin E effective at killing cancer cells but not normal cells. alpha -TEA alone and together with methylseleninic acid (MSA) and trans-resveratrol (t-RES) were investigated for ability to induce apoptosis, DNA synthesis arrest, and cellular differentiation and inhibit colony formation in human MDA-MB-435-F-L breast cancer cells in culture. The 3 agents alone were effective in inhibiting cell growth by each of the 4 different assays, and 3-way combination treatments synergistically inhibited cell proliferation in each assay in comparison to individual treatments. Furthermore, combinations of alpha -TEA, t-RES, and MSA significantly enhanced levels of apoptosis in human breast (MDA-MB-231, MCF7, and T47D) and prostate (LnCaP, PC-3, and DU-145) cancer cell lines as well as in immortalized but nontumorigenic MCF10A cells but not primary cultures of human mammary epithelial cells. Western immunoblotting confirmed the induction of apoptosis in that the 3 agents induced poly(adenosine diphosphate-ribose) polymerase cleavage, with earlier detection and more complete cleavage seen in the combination treatment. Mechanistic studies showed combination treatments to inhibit cell proliferation via downregulation of cyclin D1 and induce apoptosis via activation of caspases 8 and 9 and downregulation of prosurvival proteins FLIP and survivin. In summary, the combination of alpha-TEA, MSA, and t-RES is more effective than single treatments for inhibiting cell proliferation, inducing cellular differentiation, and inducing cell death by apoptosis in human cancer cells in culture. PMID:18444175

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  18. 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

    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

    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

  19. Alleviation of salt-induced photosynthesis and growth inhibition by salicylic acid involves glycinebetaine and ethylene in mungbean (Vigna radiata L.).

    PubMed

    Khan, M Iqbal R; Asgher, M; Khan, Nafees A

    2014-07-01

    The influence of salicylic acid (SA) in alleviation of salt stress in mungbean (Vigna radiata L.) through modulation of glycinebetaine (GB) and ethylene was studied. SA application at 0.5 mM increased methionine (Met) and GB accumulation in plants concomitant with the suppression of ethylene formation by inhibiting 1-aminocyclopropane carboxylic acid synthase (ACS) activity more conspicuously under salt stress than no stress. The increased GB accumulation together with reduced ethylene under salt stress by SA application was associated with increased glutathione (GSH) content and lower oxidative stress. These positive effects on plant metabolism induced by SA application led to improved photosynthesis and growth under salt stress. These results suggest that SA induces GB accumulation through increased Met and suppresses ethylene formation under salt stress and enhances antioxidant system resulting in alleviation of adverse effects of salt stress on photosynthesis and growth. These effects of SA were substantiated by the findings that application of SA-analogue, 2, 6, dichloro-isonicotinic acid (INA) and ethylene biosynthesis inhibitor, aminoethoxyvinylglycine (AVG) resulted in similar effects on Met, GB, ethylene production, photosynthesis and growth under salt stress. Future studies on the interaction between SA, GB and ethylene could be exploited for adaptive responses of plants under salt stress. PMID:24727790

  20. Methylseleninic acid elevates REDD1 and inhibits prostate cancer cell growth despite AKT activation and mTOR dysregulation in hypoxia

    PubMed Central

    Sinha, Indu; Allen, Joshua E; Pinto, John T; Sinha, Raghu

    2014-01-01

    Methylseleninic acid (MSeA) is a monomethylated selenium metabolite theoretically derived from subsequent ?-lyase or transamination reactions of dietary Se-methylselenocysteine that has potent antitumor activity by inhibiting cell proliferation of several cancers. Our previous studies showed that MSeA promotes apoptosis in invasive prostate cancer cells in part by downregulating hypoxia-inducible factor HIF-1?. We have now extended these studies to evaluate the impact of MSeA on REDD1 (an mTOR inhibitor) in inducing cell death of invasive prostate cancer cells in hypoxia. In both PTEN+ and PTEN? prostate cancer cells we show that MSeA elevates REDD1 and phosphorylation of AKT along with p70S6K in hypoxia. Furthermore, REDD1 induction by MSeA is independent of AKT and the mTOR inhibition in prostate cancer cells causes partial resistance to MSeA-induced growth reduction in hypoxia. Our data suggest that MSeA induces REDD1 and inhibits prostate cancer cell growth in hypoxia despite activation of AKT and dysregulation of mTOR. MSeA elevates REDD1 and AKT to promote cell death in invasive prostate cancer cells in hypoxia. PMID:24515947

  1. Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (?-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo

    PubMed Central

    Zhang, Hao; Zheng, Donghui; Ding, Jing; Xu, Huae; Li, Xiaolin; Sun, Weihao

    2015-01-01

    Previous reports have shown that ursolic acid (UA), a pentacyclic triterpenoid derived from Catharanthus trichophyllus roots, could inhibit the growth of a series of cancer cells. However, the potential for clinical application of UA is greatly hampered by its poor solubility, whereas the hydrophobicity of UA renders it a promising model drug for nanosized delivery systems. In the current study, we loaded UA into amphiphilic poly(N-vinylpyrrolidone)-block-poly (?-caprolactone) nanoparticles and performed physiochemical characterization as well as analysis of the releasing capacity. In vitro experiments indicated that UA-NPs inhibited the growth of liver cancer cells and induced cellular apoptosis more efficiently than did free UA. Moreover, UA-NPs significantly delayed tumor growth and localized to the tumor site when compared with the equivalent dose of UA. In addition, both Western blotting and immunohistochemistry suggested that the possible mechanism of the superior efficiency of UA-NPs is mediation by the regulation of apoptosis-related proteins. Therefore, UA-NPs show potential as a promising nanosized drug system for liver cancer therapy.

  2. Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (?-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo.

    PubMed

    Zhang, Hao; Zheng, Donghui; Ding, Jing; Xu, Huae; Li, Xiaolin; Sun, Weihao

    2015-01-01

    Previous reports have shown that ursolic acid (UA), a pentacyclic triterpenoid derived from Catharanthus trichophyllus roots, could inhibit the growth of a series of cancer cells. However, the potential for clinical application of UA is greatly hampered by its poor solubility, whereas the hydrophobicity of UA renders it a promising model drug for nanosized delivery systems. In the current study, we loaded UA into amphiphilic poly(N-vinylpyrrolidone)-block-poly (?-caprolactone) nanoparticles and performed physiochemical characterization as well as analysis of the releasing capacity. In vitro experiments indicated that UA-NPs inhibited the growth of liver cancer cells and induced cellular apoptosis more efficiently than did free UA. Moreover, UA-NPs significantly delayed tumor growth and localized to the tumor site when compared with the equivalent dose of UA. In addition, both Western blotting and immunohistochemistry suggested that the possible mechanism of the superior efficiency of UA-NPs is mediation by the regulation of apoptosis-related proteins. Therefore, UA-NPs show potential as a promising nanosized drug system for liver cancer therapy. PMID:25792825

  3. Anti-gene peptide nucleic acid specifically inhibits MYCN expression in human neuroblastoma cells leading to cell growth inhibition and apoptosis.

    PubMed

    Tonelli, Roberto; Purgato, Stefania; Camerin, Consuelo; Fronza, Raffaele; Bologna, Fabrizio; Alboresi, Simone; Franzoni, Monica; Corradini, Roberto; Sforza, Stefano; Faccini, Andrea; Shohet, Jason M; Marchelli, Rosangela; Pession, Andrea

    2005-05-01

    We developed an anti-gene peptide nucleic acid (PNA) for selective inhibition of MYCN transcription in neuroblastoma cells, targeted against a unique sequence in the antisense DNA strand of exon 2 of MYCN and linked at its NH(2) terminus to a nuclear localization signal peptide. Fluorescence microscopy showed specific nuclear delivery of the PNA in six human neuroblastoma cell lines: GI-LI-N and IMR-32 (MYCN-amplified/overexpressed); SJ-N-KP and NB-100 (MYCN-unamplified/low-expressed); and GI-CA-N and GI-ME-N (MYCN-unamplified/unexpressed). Antiproliferative effects were observable at 24 hours (GI-LI-N, 60%; IMR-32, 70%) and peaked at 72 hours (GI-LI-N, 80%; IMR-32, 90%; SK-N-KP, 60%; NB-100, 50%); no reduction was recorded for GI-CA-N and GI-ME-N (controls). In MYCN-amplified/overexpressed IMR-32 cells and MYCN-unamplified/low-expressed SJ-N-KP cells, inhibition was recorded of MYCN mRNA (by real-time PCR) and N-Myc (Western blotting); these inhibitory effects increased over 3 days after single treatment in IMR-32. Anti-gene PNA induced G(1)-phase accumulation (39-53%) in IMR-32 and apoptosis (56% annexin V-positive cells at 24 hours in IMR-32 and 22% annexin V-positive cells at 48 hours in SJ-N-KP). Selective activity of the PNA was shown by altering three point mutations, and by the observation that an anti-gene PNA targeted against the noncoding DNA strand did not exert any effect. These findings could encourage research into development of an anti-gene PNA-based tumor-specific agent for neuroblastoma (and other neoplasms) with MYCN expression. PMID:15897242

  4. Secreted protein acidic and rich in cysteine inhibits the growth of human pancreatic cancer cells with G1 arrest induction.

    PubMed

    Mao, Zhengfa; Ma, Xiaoyan; Fan, Xin; Cui, Lei; Zhu, Ting; Qu, Jianguo; Zhang, Jianxin; Wang, Xuqing

    2014-10-01

    Aberrant secreted protein acidic and rich in cysteine (SPARC) expression has been reported to play an important role in the tumor development. However, the pattern and the role of SPARC in pancreatic cancer remain largely unknown. Therefore, we further deciphered the role of SPARC played in pancreatic cancer. We first evaluated the SPARC expression in human pancreatic cancer tissues and pancreatic cancer cells. Then we forced expression and silenced SPARC expression in pancreatic cancer cell lines MIA PaCa2 and PANC-1, respectively, using lentivirus vectors. We characterized the stable cells in vitro. In this study, we found that SPARC expression was weak in cancer cells in specimens which negatively correlated with the expression level of phosphorylated pRB and poorer outcome. Moreover, our results demonstrated that SPARC negatively regulated pancreatic cell growth in vitro. Furthermore, we disclosed that the activation of p53 and p27(Kip1) may involve in the effect of SPARC on pancreatic cancer cells. SPARC is downregulated in pancreatic cancer cells and retards the growth of pancreatic cancer cell. Taken together, these results indicate SPARC may be a potential target for pancreatic cancer therapy. PMID:25027401

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

    PubMed

    Sparling, D W

    1990-01-01

    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. PMID:2353844

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

    USGS Publications Warehouse

    Robbins, C.S.

    1990-01-01

    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.

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

    SciTech Connect

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

    2013-08-02

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

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

    PubMed Central

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

    2014-01-01

    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

  9. Exploration of effects of emodin in selected cancer cell lines: enhanced growth inhibition by ascorbic acid and regulation of LRP1 and AR under hypoxia-like conditions.

    PubMed

    Masaldan, Shashank; Iyer, Vidhya V

    2014-01-01

    This study explores the link between the antiproliferative activity of emodin through the generation of reactive oxygen species (ROS) in various cancer cell lines and the expression of the androgen receptor (AR) in the prostate cancer cell lines LNCaP (androgen-sensitive) and PC-3 (androgen-refractory), as well as the pro-metastatic low-density lipoprotein receptor-related protein 1 (LRP1) in the above prostate cancer cells and the nonprostate cell lines A549 (lung), HCT-15 (colon) and MG-63 (bone) under normoxic and hypoxia-like conditions. Among all cell lines, emodin showed most growth inhibition in LNCaP, followed by A549. The mechanism of cytotoxicity of emodin was postulated to be the widely reported ROS generation, based on the observations of poor in vitro radical-scavenging activity and increased growth inhibition of emodin by ascorbic acid (AA) pre-treatment owing to the additive effects of ROS generation by emodin and pro-oxidant effects of AA. Emodin downregulated AR in LNCaP under normoxic and hypoxia-like conditions (simulated by CoCl(2)) and LRP1 under normoxia. Emodin upregulated LRP1 in other cell lines, except HCT-15, under normoxic, and even more markedly under hypoxia-like conditions. The downregulation of AR in LNCaP and upregulation of LRP1 in all cell lines, except HCT-15, under hypoxia-like conditions along with growth inhibition by emodin, suggests that emodin may be a useful therapeutic option against androgen-sensitive prostate cancer and other such LRP1-expressing cancers to attempt the targeting of the elevated LRP1 levels to allow the uptake of emodin and/or any other accompanying therapeutic agents by LRP1. PMID:23212659

  10. Amplified lipid rafts of malignant cells constitute a target for inhibition of aberrantly active NFAT and melanoma tumor growth by the aminobisphosphonate zoledronic acid.

    PubMed

    Levin-Gromiko, Uliana; Koshelev, Valeria; Kushnir, Paz; Fedida-Metula, Shlomit; Voronov, Elena; Fishman, Daniel

    2014-11-01

    Nuclear factors of activated T cells (NFAT) are critical modulators of cancer cell growth and survival. However, the mechanisms of their oncogenic dysregulation and strategies for targeting in tumors remain elusive. Here, we report coupling of anti- apoptotic NFAT (NFAT2) activation to cholesterol-enriched lipid raft microdomains of malignant melanoma cells and interruption of this pathway by the aminobisphosphonate zoledronic acid (Zol). The pathway was indicated by capability of Zol to promote apoptosis and to retard in vivo outgrowth of tumorigenic melanoma cell variants through inhibition of permanently active NFAT2. NFAT2 inhibition resulted from disintegration of cholesterol-enriched rafts due to reduction of cellular cholesterol by Zol. Mechanistically, raft disruption abolished raft-localized robust store-operated Ca(2+) (SOC) entry, blocking constitutive activation of protein kinase B/Akt (PKB) and thereby reactivating the NFAT repressor glycogen synthase kinase 3? (GSK3?). Pro-apoptotic inactivation of NFAT2 also followed reactivation of GSK3? by direct inhibition of PKB or SOC, whereas GSK3? blockade prevented Zol-induced NFAT2 inhibition and cell death. The rescuing effect of GSK3? blockade was reproduced by recovery of entire SOC/PKB/GSK3? cascade after reconstitution of rafts by cholesterol replenishment of Zol-treated tumorigenic cells. Remarkably, these malignant cells displayed higher cholesterol and lipid raft content than non-tumorigenic cells, which expressed weak SOC, PKB and NFAT2 activities and resisted raft-ablating action of Zol. Together, the results underscore the functional relevance of amplified melanoma rafts for tumor-promoting NFAT2 signaling and reveal these distinctive microdomains as a target for in vitro and in vivo demise of tumorigenic cells through NFAT2 inhibition by the clinical agent Zol. PMID:25142972

  11. The Ellagic Acid Derivative 4,4'-Di-O-Methylellagic Acid Efficiently Inhibits Colon Cancer Cell Growth through a Mechanism Involving WNT16.

    PubMed

    Ramírez de Molina, Ana; Vargas, Teodoro; Molina, Susana; Sánchez, Jenifer; Martínez-Romero, Jorge; González-Vallinas, Margarita; Martín-Hernández, Roberto; Sánchez-Martínez, Ruth; Gómez de Cedrón, Marta; Dávalos, Alberto; Calani, Luca; Del Rio, Daniele; González-Sarrías, Antonio; Espín, Juan Carlos; Tomás-Barberán, Francisco A; Reglero, Guillermo

    2015-05-01

    Ellagic acid (EA) and some derivatives have been reported to inhibit cancer cell proliferation, induce cell cycle arrest, and modulate some important cellular processes related to cancer. This study aimed to identify possible structure-activity relationships of EA and some in vivo derivatives in their antiproliferative effect on both human colon cancer and normal cells, and to compare this activity with that of other polyphenols. Our results showed that 4,4'-di-O-methylellagic acid (4,4'-DiOMEA) was the most effective compound in the inhibition of colon cancer cell proliferation. 4,4'-DiOMEA was 13-fold more effective than other compounds of the same family. In addition, 4,4'-DiOMEA was very active against colon cancer cells resistant to the chemotherapeutic agent 5-fluoracil, whereas no effect was observed in nonmalignant colon cells. Moreover, no correlation between antiproliferative and antioxidant activities was found, further supporting that structure differences might result in dissimilar molecular targets involved in their differential effects. Finally, microarray analysis revealed that 4,4'-DiOMEA modulated Wnt signaling, which might be involved in the potential antitumor action of this compound. Our results suggest that structural-activity differences between EA and 4,4'-DiOMEA might constitute the basis for a new strategy in anticancer drug discovery based on these chemical modifications. PMID:25758919

  12. Retinoic acid receptor beta2 re-expression and growth inhibition in thyroid carcinoma cell lines after 5-aza-2'-deoxycytidine treatment.

    PubMed

    Miasaki, F Y; Vivaldi, A; Ciampi, R; Agate, L; Collecchi, P; Capodanno, A; Pinchera, A; Elisei, R

    2008-08-01

    The treatment of both undifferentiated and de-differentiated thyroid tumors, which are unresponsive to radioiodine, represents one of the biggest challenges for thyroidologists. The aim of the present study was to investigate in vitro the methylation status of retinoic acid receptors (RAR)beta2 promoter and the effect of the demethylating agent 5-aza-2'-deoxycytidine (5-Aza-CdR) on 5 human thyroid cancer cell lines. The methylation status of RARbeta2 promoter was analyzed by methylation-specific PCR. The effect of 5-Aza-CdR on cell growth and apoptosis was evaluated by cell counting, enzymelinked immunosorbent assay tests and fluorescence-activated cell sorting analysis, while the effect on the expression of RAR and thyroid-specific genes was measured by qualitative and quantitative RT-PCR. Methylation of RARbeta2 promoter was present only in ARO cells. 5-Aza-CdR determined growth inhibition in all cell lines, probably due to apoptosis in WRO, NPA, and ARO cells, and to inhibition of DNA synthesis in TT cells. Treatment with 5-Aza-CdR induced the expression of RARbeta mRNA in ARO and FRO cells, a slight increase of the expression of Tg, TPO and thyroid trancription factor 1 (TTF-1) mRNA and the new expression of low levels of NIS in TT cells. A significant increase of TTF-1 mRNA in FRO cells was also observed. In this study we demonstrated that RARbeta2 promoter was methylated in ARO cell line. However, the 5-Aza-CdR treatment induced RARbetamRNA expression not only in ARO but also in FRO and TT cell lines, whose RARbeta2 promoter was unmethylated. A significant reduction of cell growth, but not cell re-differentiation, was also observed after 5-Aza-CdR treatment. PMID:18852534

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2015-05-01

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

  15. 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

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

    2015-03-01

    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

  16. Desalted Cod Spoilage Flora Inhibition by Citric Acid and Potassium Sorbate Combination

    Microsoft Academic Search

    Sónia Pedro; Irineu Batista; M. Leonor Nunes; M. Fernando Bernardo

    2004-01-01

    Desalted cod spoilage isolates were tested in culture broth for growth inhibition by citric acid and potassium sorbate. Preservative effect was also evaluated in refrigeratedcod juice and desalted cod spiked with Shewanella putrefaciens and Pseudomonas fluorescens orputida. Combination of 0.15% citric acid and 0.1% potassium sorbate inhibited growth of approximately 60% of isolates, including the former two strains. Total inhibition

  17. Somatostatin inhibits deoxyribonucleic acid synthesis induced by both thyrotropin and insulin-like growth factor-I in FRTL5 cells.

    PubMed

    Tsuzaki, S; Moses, A C

    1990-06-01

    Somatostatin, a cyclic tetradecapeptide, is both a hypothalamic hormone and a paracrine peptide, with effects on many tissues. Despite the fact that somatostatin can inhibit various cellular events in a number of cell lines, somatostatin is a constituent of medium defined for optimal growth of FRTL5, a line of differentiated and nontransformed rat thyroid follicular cells. In the present study we have evaluated the role of somatostatin in the control of DNA synthesis in FRTL5 cells and have investigated the mechanisms of somatostatin interaction with pathways stimulated by TSH and insulin-like growth factor-I (IGF-I). Somatostatin inhibits TSH-stimulated DNA synthesis and cell proliferation in FRTL5 cells. Maximal effects are observed at somatostatin concentrations of 0.1-10 ng/ml, and the effects are diminished at somatostatin concentrations above 10 ng/ml. Somatostatin also inhibits (Bu)2cAMP-stimulated DNA synthesis, suggesting that the loci of somatostatin action are both proximal and distal to activation of adenylate cyclase. Somatostatin also inhibits DNA synthesis stimulated by insulin-like growth factor-I (IGF-I), a pleiotropic growth factor that works through non-cAMP-dependent pathways. The somatostatin analog octreotide is more potent than native somatostatin in inhibiting DNA synthesis stimulated by either TSH or IGF-I. Somatostatin does not alter TSH or IGF-I binding to FRTL5, demonstrating that somatostatin affects the postreceptor signal transduction pathways stimulated by these factors. We conclude that 1) the use of somatostatin in hormone-supplemented medium for FRTL5 is unnecessary and may inhibit cell growth; 2) somatostatin can inhibit the direct effects of IGF-I on peripheral tissues in addition to its ability to interfere with IGF-I synthesis by inhibiting the synthesis and release of pituitary GH; and 3) somatostatin is a useful tool for dissecting the pathways involved in mediating differentiated function and growth of FRTL5 cells. PMID:1972059

  18. Well having inhibited microbial growth

    DOEpatents

    Lee, Brady D.; Dooley, Kirk J.

    2006-08-15

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

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

    Microsoft Academic Search

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

    2007-01-01

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

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

    SciTech Connect

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

    1990-08-01

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

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

    PubMed

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

    2013-02-01

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

  2. Influence of ethylenediaminetetraacetic acid (EDTA) on the on the ability of fatty acids to inhibit the growth of bacteria associated with poultry processing.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of ethylenediaminetetraacetic acid (EDTA) on the bactericidal activity of alkaline salts of fatty acids was examined. A 0.5 M concentration of caproic, caprylic, capric, and lauric acids was dissolved in 1.0 M potassium hydroxide (KOH), and then supplemented with 0, 5, or 10 mM of EDTA. T...

  3. Expression of retinoic acid receptor-beta sensitizes prostate cancer cells to growth inhibition mediated by combinations of retinoids and a 19-nor hexafluoride vitamin D3 analog.

    PubMed

    Campbell, M J; Park, S; Uskokovic, M R; Dawson, M I; Koeffler, H P

    1998-04-01

    Retinoids and analogs of vitamin D3 may achieve greater in vivo applications if the toxic side effects encountered at pharmacologically active doses could be alleviated. These seco-steroid hormones often act in concert, and therefore, we attempted to dissect these interactions by isolating combinations of receptor-selective retinoids and a potent vitamin D3 analog [1alpha,25(OH)2-16ene-23-yne-26,27,F6-19nor-D3, code name LH] that were potent inhibitors of prostate cancer cell growth at low, physiologically safer doses. Using a panel of prostate cancer cell lines representing progressively more transformed phenotypes, we found that the LNCaP cell line (least transformed) was either additively or synergistically inhibited in its clonal growth by LH and various naturally occurring and receptor-selective retinoids, the most potent combination being with a retinoic acid receptor (RAR)betagamma-selective retinoid (SR11262). The effect was not found with either PC-3 (intermediate transformation) or DU-145 (most transformed). We also undertook RT-PCR to examine the subtypes of RARs present, and we found that PC-3 and DU-145 did not express RARbeta. Stable expression of RARbeta into the RARbeta-negative PC-3 cells resulted in increased sensitivity to SR11262 and LH proportional to the amount of RARbeta expressed. This study indicates that RARbeta may play an important role in synergistically controlling cell proliferation, and expression is lost with increased prostate cancer cell transformation. Simultaneous administration of a potent vitamin D3 analog and receptor-selective retinoids may have therapeutic potential for the treatment of androgen-dependent and -independent prostate cancer. PMID:9528984

  4. Novel Bioactivity of Ellagic Acid in Inhibiting Human Platelet Activation

    PubMed Central

    Chang, Yi; Chen, Wei-Fan; Lin, Kuan-Hung; Hsieh, Cheng-Ying; Chou, Duen-Suey; Lin, Li-Jyun; Sheu, Joen-Rong; Chang, Chao-Chien

    2013-01-01

    Pomegranates are widely consumed either as fresh fruit or in beverage form as juice and wine. Ellagic acid possesses potent antioxidative properties; it is known to be an effective phytotherapeutic agent with antimutagenic and anticarcinogenic qualities. Ellagic acid (20 to 80??M) exhibited a potent activity in inhibiting platelet aggregation stimulated by collagen; however, it did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or U46619. Treatment with ellagic acid (50 and 80??M) significantly inhibited platelet activation stimulated by collagen; this alteration was accompanied by the inhibition of relative [Ca2+]i mobilization, and the phosphorylation of phospholipase C (PLC)?2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt, as well as hydroxyl radical (OH?) formation. In addition, ellagic acid also inhibited p38 MAPK and Akt phosphorylation stimulated by hydrogen peroxide. By contrast, ellagic acid did not significantly affect PKC activation and platelet aggregation stimulated by PDBu. This study is the first to show that, in addition to being considered a possible agent for preventing tumor growth, ellagic acid possesses potent antiplatelet properties. It appears to initially inhibit the PLC?2-PKC cascade and/or hydroxyl radical formation, followed by decreased phosphorylation of MAPKs and Akt, ultimately inhibiting platelet aggregation. PMID:23533502

  5. Inhibition and Facilitation of Nucleic Acid Amplification

    Microsoft Academic Search

    IAN G. WILSON

    1997-01-01

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

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

    SciTech Connect

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

    2012-04-15

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

  7. Taurolidine Inhibits Tumor Cell Growth In Vitro and In Vivo

    Microsoft Academic Search

    Morgan McCourt; Jiang Huai Wang; Shastri Sookhai; H. Paul Redmond

    2000-01-01

    Background: Taurolidine, a derivative of the amino acid taurine, exhibits antiendotoxin, antibacterial, and antiadherence activity. We hypothesized that Taurolidine may inhibit tumor cell growth, both in an in vitro and in vivo setting. Our aim was to examine the effect of Taurolidine on the growth of a rat metastatic colorectal tumor cell line (DHD\\/K12\\/TRb) in vitro and in vivo.Methods: In

  8. Plant pathology Growth inhibition of Agaricus bisporus

    E-print Network

    Paris-Sud XI, Université de

    Plant pathology Growth inhibition of Agaricus bisporus and associated thermophilic species limited the radial growth of A bisporus mycelium. The IC50 values of benomyl, carbendazim, flusilazol fortement li- mitée que par le tébuconazole. Les valeurs de CI50 du bénomyl, du carbendazime, du flusilazole

  9. Specific bile acids inhibit hepatic fatty acid uptake

    PubMed Central

    Nie, Biao; Park, Hyo Min; Kazantzis, Melissa; Lin, Min; Henkin, Amy; Ng, Stephanie; Song, Sujin; Chen, Yuli; Tran, Heather; Lai, Robin; Her, Chris; Maher, Jacquelyn J.; Forman, Barry M.; Stahl, Andreas

    2012-01-01

    Bile acids are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism. Here we tested the novel hypothesis that naturally occurring bile acids interfere with protein-mediated hepatic long chain free fatty acid (LCFA) uptake. To this end stable cell lines expressing fatty acid transporters as well as primary hepatocytes from mouse and human livers were incubated with primary and secondary bile acids to determine their effects on LCFA uptake rates. We identified ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) as the two most potent inhibitors of the liver-specific fatty acid transport protein 5 (FATP5). Both UDCA and DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. Subsequently, mice were treated with these secondary bile acids in vivo to assess their ability to inhibit diet-induced hepatic triglyceride accumulation. Administration of DCA in vivo via injection or as part of a high-fat diet significantly inhibited hepatic fatty acid uptake and reduced liver triglycerides by more than 50%. In summary, the data demonstrate a novel role for specific bile acids, and the secondary bile acid DCA in particular, in the regulation of hepatic LCFA uptake. The results illuminate a previously unappreciated means by which specific bile acids, such as UDCA and DCA, can impact hepatic triglyceride metabolism and may lead to novel approaches to combat obesity-associated fatty liver disease. PMID:22531947

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

    PubMed Central

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

    2014-01-01

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

  11. Retinoic acid regulates growth hormone gene expression

    Microsoft Academic Search

    Gabriela Bedo; Pilar Santisteban; Ana Aranda

    1989-01-01

    VITAMIN A is required for normal growth and development, and retinoic acid (RA) may be the active metabolite in this process1. Recent evidence indicates that RA acts through binding to a nuclear receptor2-5 which belongs to the steroid\\/thyroid hormone receptor superfamily6. The receptors seem to associate with hormone-response elements in the target genes resulting in the activation (or inhibition) of

  12. Growth of transplastomic cells expressing D-amino acid oxidase in chloroplasts is tolerant to D-alanine and inhibited by D-valine.

    PubMed

    Gisby, Martin F; Mudd, Elisabeth A; Day, Anil

    2012-12-01

    Dual-conditional positive/negative selection markers are versatile genetic tools for manipulating genomes. Plastid genomes are relatively small and conserved DNA molecules that can be manipulated precisely by homologous recombination. High-yield expression of recombinant products and maternal inheritance of plastid-encoded traits make plastids attractive sites for modification. Here, we describe the cloning and expression of a dao gene encoding D-amino acid oxidase from Schizosaccharomyces pombe in tobacco (Nicotiana tabacum) plastids. The results provide genetic evidence for the uptake of D-amino acids into plastids, which contain a target that is inhibited by D-alanine. Importantly, this nonantibiotic-based selection system allows the use of cheap and widely available D-amino acids, which are relatively nontoxic to animals and microbes, to either select against (D-valine) or for (D-alanine) cells containing transgenic plastids. Positive/negative selection with d-amino acids was effective in vitro and against transplastomic seedlings grown in soil. The dual functionality of dao is highly suited to the polyploid plastid compartment, where it can be used to provide tolerance against potential D-alanine-based herbicides, control the timing of recombination events such as marker excision, influence the segregation of transgenic plastid genomes, identify loci affecting dao function in mutant screens, and develop D-valine-based methods to manage the spread of transgenic plastids tagged with dao. PMID:23085840

  13. Aliphatic fatty acids and esters: inhibition of growth and exoenzyme production of Candida, and their cytotoxicity in vitro: anti-Candida effect and cytotoxicity of fatty acids and esters.

    PubMed

    Souza, Juliana L S; da Silva, Adriana F; Carvalho, Pedro H A; Pacheco, Bruna S; Pereira, Cláudio M P; Lund, Rafael G

    2014-09-01

    The secretion of extracellular phospholipases and proteinases of Candida has been described as a relevant virulence factor in human infections. Aliphatic fatty acids have antimicrobial properties, but the mechanism by which they affect the virulence factors of microorganisms, such as Candida, is still unclear, and there are a few reports about their toxicity. The current study investigated the in vitro antifungal activity, exoenzyme production and cytotoxicity of some aliphatic fatty acids and their ester derivatives against the Candida species. The minimum inhibitory concentration and minimum fungicidal concentrations of aliphatic medium-chain fatty acids, methyl and ethyl esters were performed using the CLSI M27-A3 method and the cytotoxicity assay was performed according to ISO 10993-5. The influence of these compounds in the inhibition of the production of hydrolytic enzymes, phospholipases and proteinases by Candida was also investigated. Data analysis was performed using the one-way ANOVA method (p?0.05). In relation to the MIC against Candida species, the fatty acid with the best result was Lauric acid, although its ester derivatives showed no activity. The inhibition of phospholipase production was more significant than the inhibition of proteinase production by Candida. Tested fatty acids revealed more than 80% cell viability in their MIC concentrations. Additionally, a cell viability of 100% was reported at concentrations of anti-enzymatic effect. Therefore, the potential use of these fatty acids could be the basis for more antimicrobial tests. PMID:24907517

  14. Growth Inhibition and Induction of Apoptosis of Colon Cancer Cell Lines by Applying Marine Phospholipid

    Microsoft Academic Search

    Zakir Hossain; Masashi Hosokawa; Koretaro Takahashi

    2008-01-01

    Polyunsaturated fatty acids (PUFAs) exhibit beneficial biological functions in carcinogenic processes. We examined the effects of PUFAs in the acid and phospholipid forms on three colon cancer cell lines (HT-29, Caco-2, and DLD-1). Docosahexaenoic acid (DHA) and eicosapentaenoic (EPA) in both acid and phospholipid forms showed growth inhibition effects on experimental colon cancer cell lines. But these PUFAs had the

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

    PubMed

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

    2014-10-01

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

  16. Inhibiting bacterial fatty acid synthesis.

    PubMed

    Zhang, Yong-Mei; White, Stephen W; Rock, Charles O

    2006-06-30

    The type II fatty acid synthase consists of a series of individual enzymes, each encoded by a separate gene, that catalyze discrete steps in chain elongation. The formation of fatty acids is vital to bacteria, and each of the essential enzymes and their acyl group carriers represent a potential target for the development of novel antibacterial therapeutics. High resolution x-ray and/or NMR structures of representative members of every enzyme in the type II pathway are now available, and these structures are a valuable resource to guide antibacterial drug discovery. The role of each enzyme in regulating pathway activity and the diversity in the components of the pathway in the major human pathogens are important considerations in deciding the most suitable targets for future drug development. PMID:16648134

  17. Dietary linoleic acid, immune inhibition and disease

    PubMed Central

    Sammon, A.

    1999-01-01

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

  18. How Does Interferon Inhibit Tumour Growth?: Discussion

    Microsoft Academic Search

    Michael Stoker

    1982-01-01

    Interferon can inhibit tumour growth in experimental animals and in some patients with benign and malignant tumours. There is experimental evidence to suggest that several mechanisms may be involved: a direct effect on the tumour or an indirect effect via the host, or both. Thus, interferon may slow the rate of tumour cell multiplication and this may lead to cell

  19. Phytic Acid Inhibits Lipid Peroxidation In Vitro

    PubMed Central

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

    2013-01-01

    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

  20. MFR PAPER 1339 Phosphonoacetic Acid Inhibition of

    E-print Network

    of DNA viruses. Mem- bers of this diverse family of viruses are found throughout the phylogeny phosphonoace- tic acid (PAA), functions specifically by inhibiting the herpesvirus coded DNA dependent DNA by trypan blue dye exclu- sion at the beginning and end (72 hours postinoculation) of each experiment in

  1. Docosahexaenoic acid inhibits vascular endothelial growth factor (VEGF)-induced cell migration via the GPR120/PP2A/ERK1/2/eNOS signaling pathway in human umbilical vein endothelial cells.

    PubMed

    Chao, Che-Yi; Lii, Chong-Kuei; Ye, Siou-Yu; Li, Chien-Chun; Lu, Chia-Yang; Lin, Ai-Hsuan; Liu, Kai-Li; Chen, Haw-Wen

    2014-05-01

    Cell migration plays an important role in angiogenesis and wound repair. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is essential for endothelial cell survival, proliferation, and migration. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, shows both anti-inflammatory and antioxidant activities in vitro and in vivo. This study investigated the molecular mechanism by which DHA down-regulates VEGF-induced cell migration. HUVECs were used as the study model, and the MTT assay, Western blot, wound-healing assay, and phosphatase activity assay were used to explore the effects of DHA on cell migration. GPR120 is the putative receptor for DHA action. The results showed that DHA, PD98059 (an ERK1/2 inhibitor), and GW9508 (a GPR120 agonist) inhibited VEGF-induced cell migration. In contrast, pretreatment with okadaic acid (OA, a PP2A inhibitor) and S-nitroso-N-acetyl-DL-penicillamine (an NO donor) reversed the inhibition of cell migration by DHA. VEGF-induced cell migration was accompanied by phosphorylation of ERK1/2 and eNOS. Treatment of HUVECs with DHA increased PP2A enzyme activity and decreased VEGF-induced phosphorylation of ERK1/2 and eNOS. However, pretreatment with OA significantly decreased DHA-induced PP2A enzyme activity and reversed the DHA inhibition of VEGF-induced ERK1/2 and eNOS phosphorylation. These results suggest that stimulation of PP2A activity and inhibition of the VEGF-induced ERK1/2/eNOS signaling pathway may be involved in the DHA suppression of VEGF-induced cell migration. Thus, the effect of DHA on angiogenesis and wound repair is at least partly by virtue of its attenuation of cell migration. PMID:24734983

  2. Understanding biocatalyst inhibition by carboxylic acids.

    PubMed

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

    2013-01-01

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

  3. {2-[1-(3-Methoxycarbonylmethyl-1H-indol-2-yl)-1-methyl-ethyl]-1H-indol-3-yl}-acetic acid methyl ester (MIAM) inhibited human hepatocellular carcinoma growth through upregulation of Sirtuin-3 (SIRT3).

    PubMed

    Li, Ye; Wang, Wenjing; Xu, Xiaoxue; Sun, Shiyue; Qu, Xian-Jun

    2015-02-01

    {2-[1-(3-Methoxycarbonylmethyl-1H-indol-2-yl)-1-methyl-ethyl]-1H-indol-3-yl}-acetic acid methyl ester (MIAM) is a novel indole compound. Our previous studies showed that MIAM possessed activity against many cancers xenografted in mice without significant toxicity. In this study, we determined the effect of MIAM on human hepatocellular carcinoma (HCC) by both in vitro and in vivo assays. In in vitro assay, the experiments were performed in the hypoxic incubator. MIAM inhibited HCC growth with dose-dependent manner. The effects of MIAM on HCC might be due to its activities in induction of apoptosis, arrest of cell cycle in G0/G1 phase. Further studies showed that MIAM might exert its actions through multiple mechanisms. MIAM could reduce intracellular ATP, increase levels of p53/p21 and SIRT3/SOD2/Bax. MIAM also had the activity of reducing HIF1? and hexokinase II (HK II) in HCC. MIAM had the activity of increasing cellular reactive oxygen species (ROS) in HCC. However, the increase of ROS might not be its main mechanism in inhibition of HCC. MIAM might inhibit HepG2 growth through induction of apoptosis. We determined the relationship between level of SIRT3 and cell viability in the MIAM-treated cells. MIAM treatment resulted in increase of SIRT3 in HCC. Further, HepG2 cells infected with human SIRT3 were more sensitive to MIAM than the cells without infection of SIRT3. These results suggested that MIAM might inhibit HCC growth through upregulation of SIRT3. Importantly, the effect of MIAM was confirmed in the HepG2 xenografts bearing in mice. MIAM treatment did not induce significant toxicology to mice. Together, MIAM could be developed as potential agent for treatment of HCC. PMID:25661348

  4. Mechanism of the inhibitory action of linoleic acid on the growth of Staphylococcus aureus.

    PubMed

    Greenway, D L; Dyke, K G

    1979-11-01

    Linoleic acid, but not stearic acid, inhibited the growth of Staphylococcus aureus NCTC 8325. Growth inhibition was associated with an increase in the permeability of the bacterial membrane. The presence of a plasmid conferring resistance to penicillin (PC plasmid, e.g. pI258blaI-) increased the growth inhibitory and membrane permeability effects of linoleic acid. Under growth inhibitory conditions, linoleic acid was incorporated into the lipid of both PC plasmid-containing and PC plasmid-negative bacteria and there was little difference between these cultures in the uptake or fate of linoleic acid. Experiments using a glycerol auxotroph of S. aureus suggested that free linoleic acid, rather than lipid containing this acid, inhibits growth. Linoleic acid probably inhibits growth by increasing the permeability of the bacterial membrane as a result of its surfactant action, and the presence of the PC plasmid increases these effects. PMID:93615

  5. Delayed fluorescence in algal growth inhibition tests

    Microsoft Academic Search

    Maja Berden-Zrimec; Luka Drinovec; Alexis Zrimec; Tatjana Tišler

    2007-01-01

    A series of 72-hour growth inhibition tests with green alga Desmodesmus (Scenedesmus) subspicatus (ISO 8692) has been performed to test the delayed fluorescence (DF) parameters as possible endpoint measurements. Sensitivity\\u000a to five toxicants with direct and indirect effects on photosynthesis was tested, and the median effective concentration (EC50) values derived from the cell concentration, absorbance and DF were compared. The

  6. Ormeloxifene efficiently inhibits ovarian cancer growth.

    PubMed

    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

    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

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

    PubMed Central

    2009-01-01

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

  8. Lipoproteins inhibit macrophage activation by lipoteichoic acid

    Microsoft Academic Search

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

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

  9. Inhibitory Action of Fatty Acids on the Growth of Neisseria gonorrhoeae

    PubMed Central

    Miller, Richard D.; Brown, Kenneth E.; Morse, Stephen A.

    1977-01-01

    Fatty acids of various chain lengths (C1 to C24) were examined for their effects on growth, oxygen consumption, and in vitro reduced nicotinamide adenine dinucleotide oxidase activity of Neisseria gonorrhoeae CS-7. The growth inhibition caused by saturated fatty acids increased with increasing chain length to a maximum with palmitic acid (C16). Stearic acid (C18) and longer saturated fatty acids showed little inhibition of growth. However, unsaturated fatty acids of chain length C16 to C20 were inhibitory. Similar inhibition was observed with Bacillus subtilis and a deep rough mutant of Salmonella typhimurium. Wildtype S. typhimurium and Pseudomonas aeruginosa were more resistant to medium-chain (C7 to C10) fatty acids and completely resistant to long-chain (C12 to C18) fatty acids. Thus, sensitivity of N. gonorrhoeae to long-chain fatty acids appears to be related to the permeability of the outer membrane. Growth inhibition by short-chain (C1 to C6) fatty acids was pH dependent; inhibition of growth increased with decreasing pH. Saturated fatty acids inhibited oxygen consumption by log-phase cells of N. gonorrhoeae. This inhibition increased with increasing chain length to a maximum observed with myristic acid (C14). Whereas stearic acid (C18) had little effect upon oxygen consumption, unsaturated C18 fatty acids were inhibitory. An in vitro inhibition of reduced nicotinamide adenine dinucleotide oxidase activity by saturated (C1 to C12) and unsaturated (C16 to C20) fatty acids was also observed. Although the inhibitory concentrations were generally higher than those required to inhibit growth or oxygen consumption, an inhibition of electron transport may be partially responsible for the observed growth inhibition. PMID:19358

  10. D440N mutation in the acid-labile subunit of insulin-like growth factor complexes inhibits secretion and complex formation.

    PubMed

    Firth, Sue M; Yan, Xiaolang; Baxter, Robert C

    2011-02-01

    The acid-labile subunit (ALS) regulates IGF bioavailability by forming heterotrimeric complexes with IGFs and IGF-binding protein-3 (IGFBP-3). A homozygous missense mutation (D440N) resulting in undetectable circulating levels of ALS with a concomitant reduction in IGF-I and IGFBP-3 has been reported to cause mild growth retardation. To understand how this particular mutation affects ALS circulating levels and IGF-transport function, we expressed recombinant ALS and its variants, D440N-ALS, T442A-ALS, and D440N/T442A-ALS, using adenovirus vectors. Compared with wild-type ALS, the secretion of D440N-ALS was 80% lower. The D440N mutation was proposed to generate an N-glycosylation site additional to the seven existing motifs in ALS. D440N-ALS appeared larger than ALS, attributable to N-linked glycans because deglycosylation with N-glycosidase F reduced both proteins to the same molecular mass. When ALS was incubated with IGF-I and IGFBP-3, 70-80% of IGF-I was detected by gel-filtration chromatography in forms corresponding to the 150-kDa ternary complex. In contrast, when D440N-ALS was tested, less than 30% of IGF-I was found in high molecular mass complexes. Two other ALS variants mutated in the same putative glycosylation site, D440N/T442A-ALS and T442A-ALS, showed similar chromatographic profiles to wild-type ALS. The D440N mutation in ALS generates a hyperglycosylated form with impaired secretion and complex formation, potentially leading to dysregulation of endocrine IGF, thus contributing to the growth retardation observed in the affected patient. This is the first study to explain how a natural mutation, D440N, in ALS impairs its function. PMID:21177759

  11. Growth inhibition and induction of apoptosis of colon cancer cell lines by applying marine phospholipid.

    PubMed

    Hossain, Zakir; Hosokawa, Masashi; Takahashi, Koretaro

    2009-01-01

    Polyunsaturated fatty acids (PUFAs) exhibit beneficial biological functions in carcinogenic processes. We examined the effects of PUFAs in the acid and phospholipid forms on three colon cancer cell lines (HT-29, Caco-2, and DLD-1). Docosahexaenoic acid (DHA) and eicosapentaenoic (EPA) in both acid and phospholipid forms showed growth inhibition effects on experimental colon cancer cell lines. But these PUFAs had the strongest growth-inhibitory effect on HT-29 than Caco-2 and DLD-1. Combined application of PUFAs and sodium butyrate (NaBt) increased the growth inhibition. Growth inhibition was apparently caused by increased lipid peroxidation. DHA or EPA in combination with NaBt significantly increased caspase-3 activity compared to control. DHA and DHA-rich phosphatidylcholine decreased Bcl-2 level in HT-29 and Caco-2 cells. PMID:19116882

  12. Equine platelets inhibit E. coli growth and can be activated by bacterial lipopolysaccharide and lipoteichoic acid although superoxide anion production does not occur and platelet activation is not associated with enhanced production by neutrophils.

    PubMed

    Aktan, I; Dunkel, B; Cunningham, F M

    2013-04-15

    Activated platelets can contribute to host defense through release of products with bactericidal actions such as antimicrobial peptides and reactive oxygen species (ROS), as well as by forming heterotypic aggregates with neutrophils and enhancing their antimicrobial properties. Whilst release of vasoactive mediators from equine platelets in response to stimuli including bacterial lipopolysaccharide (LPS) has been documented, neither ROS production, nor the effects of activated platelets on equine neutrophil ROS production, have been reported. This study first sought evidence that activated equine platelets inhibit bacterial growth. Platelet superoxide production in response to stimuli including Escherichia coli-derived LPS and lipoteichoic acid (LTA) from Staphylococcus aureus was then determined. The ability of LPS and LTA to up-regulate platelet P-selectin expression and induce platelet-neutrophil aggregate formation was investigated and the effect of co-incubating activated platelets with neutrophils on superoxide production measured. Growth of E. coli was inhibited in a time-dependent manner, and to a similar extent, by addition of platelet rich plasma (PRP) or platelet poor plasma (PPP) obtained by centrifugation of PRP. Activation of platelets in PRP by addition of thrombin led to a significant increase in the inhibitory action between 0.5 and 2h. Although phorbol myristate acetate (PMA) caused superoxide production by equine platelets in a protein kinase C-dependent manner, thrombin, platelet activating factor (PAF), LPS, LTA and formyl-methionyl-leucyl phenylalanine (FMLP) were without effect. LPS and LTA did induce platelet activation, measured as an increase in P-selectin expression (% positive cells: 17±3 (un-stimulated); 63±6 (1?g/ml LPS); 64±6 (1?g/ml LTA); n=5) but not platelet superoxide production or heterotypic aggregate formation. Co-incubation of activated platelets with neutrophils did not increase neutrophil superoxide production. This study has demonstrated for the first time that when activated, equine platelets, like those of other species, are capable of releasing ROS that could assist in bacterial killing. However, the findings suggest that neither superoxide production by platelets nor enhancement of production by neutrophils is likely to play a significant role. Nevertheless, as has been reported in man, equine PPP and PRP did inhibit E. coli growth in vitro, and addition of thrombin significantly increased the inhibitory effect of PRP. This suggests that products released from activated platelets could contribute to antimicrobial activity in the horse. The factors in equine plasma and released by activated platelets that are responsible for inhibiting bacterial growth have yet to be determined. PMID:23332730

  13. Caffeic acid phenethyl ester reduces the secretion of vascular endothelial growth factor through the inhibition of the ROS, PI3K and HIF-1? signaling pathways in human retinal pigment epithelial cells under hypoxic conditions.

    PubMed

    Paeng, Sung Hwa; Jung, Won-Kyo; Park, Won Sun; Lee, Dae-Sung; Kim, Gi-Young; Choi, Yung Hyun; Seo, Su-Kil; Jang, Won Hee; Choi, Jung Sik; Lee, Young-Min; Park, Saegwang; Choi, Il-Whan

    2015-05-01

    Choroidal neovascularization (CNV) can lead to progressive and severe visual loss. Vascular endothelial growth factor (VEGF) promotes the development of CNV. Caffeic acid phenethyl ester (CAPE), a biologically active component of the honeybee (Apis mellifera) propolis, has been demonstrated to have several interesting biological regulatory properties. The objective of this study was to determine whether treatment with CAPE results in the inhibition of the production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial cells (RPE cells) under hypoxic conditions and to explore the possible underlying mechanisms. An in vitro experimental model of hypoxia was used to mimic an ischemic microenvironment for the RPE cells. Human RPE cells (ARPE-19) were exposed to hypoxia with or without CAPE pre-treatment. ARPE-19 cells were used to investigate the pathway involved in the regulation of VEGF production under hypoxic conditions, based on western blot analysis, enzyme-linked immunosorbent assay (ELISA) and electrophoretic mobility shift assay (EMSA). The amount of VEGF released from the hypoxia?exposed cells was significantly higher than that of the normoxic controls. Pre-treatment with CAPE suppressed the hypoxia-induced production of VEGF in the ARPE-19 cells, and this effect was inhibited through the attenuation of reactive oxygen species (ROS) production, and the inhibition of phosphoinositide 3-kinase (PI3K)/AKT and hypoxia-inducible factor-1? (HIF-1?) expression. These in vitro findings suggest that CAPE may prove to be a novel anti-angiogenic agent for the treatment of diseases associated with CNV. PMID:25738890

  14. Selenium nanoparticles inhibit Staphylococcus aureus growth

    PubMed Central

    Tran, Phong A; Webster, Thomas J

    2011-01-01

    Staphylococcus aureus is a key bacterium commonly found in numerous infections. S. aureus infections are difficult to treat due to their biofilm formation and documented antibiotic resistance. While selenium has been used for a wide range of applications including anticancer applications, the effects of selenium nanoparticles on microorganisms remain largely unknown to date. The objective of this in vitro study was thus to examine the growth of S. aureus in the presence of selenium nanoparticles. Results of this study provided the first evidence of strongly inhibited growth of S. aureus in the presence of selenium nanoparticles after 3, 4, and 5 hours at 7.8, 15.5, and 31 ?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

  15. Stanniocalcin-2 inhibits mammalian growth by proteolytic inhibition of the insulin-like growth factor axis.

    PubMed

    Jepsen, Malene R; Kløverpris, Søren; Mikkelsen, Jakob H; Pedersen, Josefine H; Füchtbauer, Ernst-Martin; Laursen, Lisbeth S; Oxvig, Claus

    2015-02-01

    Mammalian stanniocalcin-2 (STC2) is a secreted polypeptide widely expressed in developing and adult tissues. However, although transgenic expression in mice is known to cause severe dwarfism, and targeted deletion of STC2 causes increased postnatal growth, its precise biological role is still unknown. We found that STC2 potently inhibits the proteolytic activity of the growth-promoting metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A). Proteolytic inhibition requires covalent binding of STC2 to PAPP-A and is mediated by a disulfide bond, which involves Cys-120 of STC2. Binding of STC2 prevents PAPP-A cleavage of insulin-like growth factor-binding protein (IGFBP)-4 and hence release within tissues of bioactive IGF, required for normal growth. Concordantly, we show that STC2 efficiently inhibits PAPP-A-mediated IGF receptor signaling in vitro and that transgenic mice expressing a mutated variant of STC2, STC2(C120A), which is unable to inhibit PAPP-A, grow like wild-type mice. Our work identifies STC2 as a novel proteinase inhibitor and a previously unrecognized extracellular component of the IGF system. PMID:25533459

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

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  17. Osteoclast inhibition impairs chondrosarcoma growth and bone destruction.

    PubMed

    Otero, Jesse E; Stevens, Jeff W; Malandra, Allison E; Fredericks, Douglas C; Odgren, Paul R; Buckwalter, Joseph A; Morcuende, Jose

    2014-12-01

    Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients. PMID:25125336

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

    Microsoft Academic Search

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

    1990-01-01

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

  19. Preliminary investigation on the presence of peptides inhibiting the growth of Listeria innocua and Listeria

    E-print Network

    Boyer, Edmond

    , salts, and organic acids, prior to freeze-drying. The growth of Listeria innocua LRGIA 01NOTE Preliminary investigation on the presence of peptides inhibiting the growth of Listeria that these peptides can exert an effective antimicrobial effect. The aim of this study was to investigate the anti

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

    PubMed Central

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

    2014-01-01

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

  1. 1,25-Dihydroxyvitamin D3 and 9-cis-Retinoic Acid Act Synergistically to Inhibit the Growth of LNCaP Prostate Cells and Cause Accumulation of Cells in G1

    Microsoft Academic Search

    SARAH E. BLUTT; ELIZABETH A. ALLEGRETTO; J. WESLEY PIKE

    1997-01-01

    Recent studies have suggested that the active metabolite of vita- min D3, 1,25-dihydroxyvitamin D3, can inhibit the growth and\\/or induce the differentiation of a variety of cell types and that these characteristics might be useful in the treatment of some cancers. Retinoids also promote the differentiation and inhibit the growth of some cells. That the vitamin D receptor acts as

  2. Cell growth inhibition by sequence-specific RNA minihelices.

    PubMed

    Hipps, D; Schimmel, P

    1995-08-15

    RNA minihelices which reconstruct the 12 base pair acceptor-T psi C domains of transfer RNAs interact with their cognate tRNA synthetases. These substrates lack the anticodons of the genetic code and, therefore, cannot participate in steps of protein synthesis subsequent to aminoacylation. We report here that expression in Escherichia coli of either of two minihelices, each specific for a different amino acid, inhibited cell growth. Inhibition appears to be due to direct competition between the minihelix and its related tRNA for binding to their common synthetase. This competition, in turn, sharply lowers the pool of the specific charged tRNA for protein synthesis. Inhibition is relieved by single nucleotide changes which disrupt the minihelix-synthetase interaction. The results suggest that sequence-specific RNA minihelix substrates bind to cognate synthetases in vivo and can, in principle, act as cell growth regulators. Naturally occurring non-tRNA substrates for aminoacylation may serve a similar purpose. PMID:7664744

  3. Cell growth inhibition by sequence-specific RNA minihelices.

    PubMed Central

    Hipps, D; Schimmel, P

    1995-01-01

    RNA minihelices which reconstruct the 12 base pair acceptor-T psi C domains of transfer RNAs interact with their cognate tRNA synthetases. These substrates lack the anticodons of the genetic code and, therefore, cannot participate in steps of protein synthesis subsequent to aminoacylation. We report here that expression in Escherichia coli of either of two minihelices, each specific for a different amino acid, inhibited cell growth. Inhibition appears to be due to direct competition between the minihelix and its related tRNA for binding to their common synthetase. This competition, in turn, sharply lowers the pool of the specific charged tRNA for protein synthesis. Inhibition is relieved by single nucleotide changes which disrupt the minihelix-synthetase interaction. The results suggest that sequence-specific RNA minihelix substrates bind to cognate synthetases in vivo and can, in principle, act as cell growth regulators. Naturally occurring non-tRNA substrates for aminoacylation may serve a similar purpose. Images PMID:7664744

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

    PubMed

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

    2015-03-30

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

  5. Azadirachtin interacts with retinoic acid receptors and inhibits retinoic acid-mediated biological responses.

    PubMed

    Thoh, Maikho; Babajan, Banaganapalli; Raghavendra, Pongali B; Sureshkumar, Chitta; Manna, Sunil K

    2011-02-11

    Considering the role of retinoids in regulation of more than 500 genes involved in cell cycle and growth arrest, a detailed understanding of the mechanism and its regulation is useful for therapy. The extract of the medicinal plant Neem (Azadirachta indica) is used against several ailments especially for anti-inflammatory, anti-itching, spermicidal, anticancer, and insecticidal activities. In this report we prove the detailed mechanism on the regulation of retinoic acid-mediated cell signaling by azadirachtin, active components of neem extract. Azadirachtin repressed all trans-retinoic acid (ATRA)-mediated nuclear transcription factor ?B (NF-?B) activation, not the DNA binding but the NF-?B-dependent gene expression. It did not inhibit I?B? degradation, I?B? kinase activity, or p65 phosphorylation and its nuclear translocation but inhibited NF-?B-dependent reporter gene expression. Azadirachtin inhibited TRAF6-mediated, but not TRAF2-mediated NF-?B activation. It inhibited ATRA-induced Sp1 and CREB (cAMP-response element-binding protein) DNA binding. Azadirachtin inhibited ATRA binding with retinoid receptors, which is supported by biochemical and in silico evidences. Azadirachtin showed strong interaction with retinoid receptors. It suppressed ATRA-mediated removal of retinoid receptors, bound with DNA by inhibiting ATRA binding to its receptors. Overall, our data suggest that azadirachtin interacts with retinoic acid receptors and suppresses ATRA binding, inhibits falling off the receptors, and activates transcription factors like CREB, Sp1, NF-?B, etc. Thus, azadirachtin exerts anti-inflammatory and anti-metastatic responses by a novel pathway that would be beneficial for further anti-inflammatory and anti-cancer therapies. PMID:21127062

  6. Mechanism of specific inhibition of phototropism by phenylacetic acid in corn seedling

    SciTech Connect

    Vierstra, R.D.; Poff, K.L.

    1981-05-01

    Using geotropism as a control for phototropism, compounds similar to phenylacetic acid that phototreact with flavins and/or have auxin-like activity were examined for their ability to specifically inhibit phototropism in corn seedlings using geotropism as a control. Results using indole-3-acetic acid, napthalene-1-acetic acid, naphthalene-2-acetic acid, phenylacetic acid, and ..beta..-phenylpyruvic acid suggest that such compounds will specifically inhibit phototropism primarily because of their photoreactivity with flavins and not their auxin activity. In addition, the in vivo concentration of phenylacetic acid required to induce specificity was well below that required to stimulate coleoptile growth. Estimates of the percentage of photoreceptor pigment inactivated by phenylacetic acid (>10%) suggest that phenylacetic acid could be used to photoaffinity label the flavoprotein involved in corn seedling phototropism.

  7. Aurin tricarboxylic acid inhibits experimental venous thrombosis.

    PubMed

    Bernat, A; Lale, A; Herbert, J M

    1994-06-15

    In vitro, aurin tricarboxylic acid (ATA) inhibited ristocetin-induced human platelet agglutination in a dose-dependent manner. The IC50 value (dose which inhibits 50% of platelet agglutination) was 60 +/- 8.7 micrograms/ml. In vivo, the i.v. administration of ATA to rats reduced the thrombus formation in an arteriovenous shunt with an ED50 value of 9.0 +/- 1.6 mg/kg. In a venous thrombosis model, using a combination of a thrombogenic challenge and stasis, ATA displayed a significant, dose-dependent antithrombotic effect, the ED50 value being of 18.3 +/- 2.0 mg/kg. In an experimental model of disseminated intravascular coagulation, ATA protected mice from the lethal effect of thromboplastin-induced thromboembolism with a ED50 value of 1.1 +/- 0.15 mg/kg, being in that respect 12 times less potent than standard heparin (ED50 = 90 +/- 15 micrograms/kg). These observations therefore show that ATA is active in both arterial- or venous-type thrombosis models and suggest that von Willebrand Factor might be important not only in arterial but also in venous thrombosis. PMID:8091404

  8. Investigations on dendrimer space reveal solid and liquid tumor growth-inhibition by original phosphorus-based dendrimers and the corresponding monomers and dendrons with ethacrynic acid motifs.

    PubMed

    El Brahmi, Nabil; Mignani, Serge M; Caron, Joachim; El Kazzouli, Saïd; Bousmina, Mosto M; Caminade, Anne-Marie; Cresteil, Thierry; Majoral, Jean-Pierre

    2015-02-19

    The well-known reactive diuretic ethacrynic acid (EA, Edecrin), with low antiproliferative activities, was chemically modified and grafted onto phosphorus dendrimers and the corresponding simple branched phosphorus dendron-like derivatives affording novel nanodevices showing moderate to strong antiproliferative activities against liquid and solid tumor cell lines, respectively. PMID:25503793

  9. A chemical pollen suppressant inhibits auxin-induced growth in maize coleoptile sections

    SciTech Connect

    Vesper, M.J. (Univ. of Dayton, OH (USA)); Cross, J.W. (Sogetal, Inc., Hayward, CA (USA))

    1990-05-01

    Chemical inhibitors of pollen development having a phenylcinnoline carboxylate structure were found to inhibit IAA- and 1-NAA-induced growth in maize coleoptile sections. The inhibitor (100 {mu}M) used in these experiments caused approx. 35% reduction in auxin-induced growth over the auxin concentration range of 0.3 to 100 {mu}M. Growth inhibition was noted as a lengthening of the latent period and a decrease in the rate of an auxin-induced growth response. An acid growth response to pH 5 buffer in abraded sections was not impaired. The velocity of basipetal transport of ({sup 3}H)IAA through the coleoptile sections also was not inhibited by the compound, nor was uptake of ({sup 3}H)IAA. Similarly, the inhibitor does not appear to alter auxin-induced H{sup +} secretion. We suggest that the agent targets some other process necessary for auxin-dependent growth.

  10. Investigations on dendrimer space reveal solid and liquid tumor growth-inhibition by original phosphorus-based dendrimers and the corresponding monomers and dendrons with ethacrynic acid motifs

    NASA Astrophysics Data System (ADS)

    El Brahmi, Nabil; Mignani, Serge M.; Caron, Joachim; El Kazzouli, Saïd; Bousmina, Mosto M.; Caminade, Anne-Marie; Cresteil, Thierry; Majoral, Jean-Pierre

    2015-02-01

    The well-known reactive diuretic ethacrynic acid (EA, Edecrin), with low antiproliferative activities, was chemically modified and grafted onto phosphorus dendrimers and the corresponding simple branched phosphorus dendron-like derivatives affording novel nanodevices showing moderate to strong antiproliferative activities against liquid and solid tumor cell lines, respectively.The well-known reactive diuretic ethacrynic acid (EA, Edecrin), with low antiproliferative activities, was chemically modified and grafted onto phosphorus dendrimers and the corresponding simple branched phosphorus dendron-like derivatives affording novel nanodevices showing moderate to strong antiproliferative activities against liquid and solid tumor cell lines, respectively. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05983b

  11. Inhibition of Aluminum Oxyhydroxide Precipitation with Citric Acid

    SciTech Connect

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

    2005-12-06

    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.

  12. Accumulation of polyhydroxyalkanoic acid containing large amounts of unsaturated monomers in Pseudomonas fluorescens BM07 utilizing saccharides and its inhibition by 2-bromooctanoic acid.

    PubMed

    Lee, H J; Choi, M H; Kim, T U; Yoon, S C

    2001-11-01

    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 (C(7)) to hexadecanoic acid (C(16)) 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 (C(18)) 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 beta-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 microM, 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 K(i) (the concentration for 50% inhibition of PHA synthesis) for 2-bromooctanoic acid was determined to be 60 microM, 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

  13. Inhibition Against Growth of Glioblastoma Multiforme In Vitro Using Etoposide-Loaded Solid Lipid Nanoparticles with p-Aminophenyl-?-d-Manno-Pyranoside and Folic Acid.

    PubMed

    Kuo, Yung-Chih; Lee, Chia-Hao

    2015-05-01

    Solid lipid nanoparticles (SLNs) grafted with p-aminophenyl-?-d-manno-pyranoside (APMP) and folic acid (FA) (APMP-FA-SLNs) were applied to encapsulate 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-?-d-glucopyranoside) (etoposide) (ETP) for promoting the antiproliferation of malignant glioblastoma multiforme. ETP-loaded APMP-FA-SLNs (APMP-FA-ETP-SLNs) were used to penetrate the blood-brain barrier (BBB) and retard the propagation of U87MG cells. An incorporation of APMP and FA increased the particle size, the cytotoxicity to U87MG cells, and the permeability coefficient for propidium iodide and ETP across the BBB. In addition, an increase in the APMP and FA concentration reduced the zeta potential, the grafting efficiency of APMP and FA, the dissolution rate of ETP, and the transendothelial electrical resistance. Immunochemical staining images evidenced that APMP-FA-ETP-SLNs could infiltrate the BBB via glucose transporter 1 and recognize U87MG cells via folate receptor. APMP-FA-ETP-SLNs can be an effective pharmacotherapeutic formulation in targeting delivery to the brain and in inhibitory efficacy against tumorous cells for cancer therapy. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1804-1814, 2015. PMID:25694089

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

    PubMed

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

    2010-01-01

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

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

    Microsoft Academic Search

    A.-P. Zeng; A. Ross; H. Biebl; C. Tag; B. Guenzel; W.-D. Deckwer

    1994-01-01

    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

  16. Influence of humic acids on laurel growth, associated rhizospheric microorganisms, and mycorrhizal fungi

    Microsoft Academic Search

    G. Vallini; A. Pera; L. Avio; M. Valdrighi; M. Giovannetti

    1993-01-01

    Increasing concentrations of humic acids were tested in order to determine their effects on the microbial rhizosphere and the growth of laurel (Laurus nobilis L.). Plants that were treated with 300 mg kg-1 of humic acids had the heaviest weights of both fresh and dry shoots; however, doses of 3000 mg kg-1 were highly phytotoxic and inhibited the growth of

  17. Inhibition of in vitro growth of enteropathogens by new Lactobacillus isolates of human intestinal origin

    Microsoft Academic Search

    Lorenzo Drago; Maria Rita Gismondo; Alessandra Lombardi; Christoph de Haën; Luigia Gozzini

    1997-01-01

    Three human Lactobacillus strains, coded B21060, B21070 and B21190, have recently been isolated. The strains show a series of features (acid and bile resistance, adhesion to various types of mucosal cell) which make them particularly promising for the preparation of probiotic products. In the present study, the ability of the strains to inhibit the growth of pathogens in coculture was

  18. Effects of fatty acids on growth and poly-3-hydroxybutyrate production in bacteria.

    PubMed

    Lo, K W; Chua, H; Lawford, H; Lo, W H; Yu, Peter H F

    2005-01-01

    The effects of saturated and unsaturated fatty acids (lauric acid, palmitic acid, steric acid, oleic acid, linoleic acid, soybean oil) on Sphaerotilus natans, 0B17 (Pseudomonas sp.), and recombinant Escherichia coli DH5(/pUC19/CAB were studied. Oleic acid enhances Poly-3-hydroxybutyrate (PHB) production in these three bacterial strains, suggesting that the single double bond of the acid activates the polyhydroxylkanoate accumulation enzymatic reaction. Under the effect of lauric acid and linoleic acid, the growth of S. natans and 0B17 were totally inhibited. However, the enhanced PHB accumulation in recombinant E. coli was observed. PMID:15920264

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

    PubMed Central

    2013-01-01

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

  20. Novel Approaches to Inhibition of Gastric Acid Secretion

    PubMed Central

    Shin, Jai Moo; Hunt, Richard

    2010-01-01

    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

  1. Novel approaches to inhibition of gastric acid secretion.

    PubMed

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

    2010-12-01

    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

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

    Microsoft Academic Search

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

    2010-01-01

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

  3. Method for concentrating antisera for preparing Mycoplasma growth inhibition discs.

    PubMed

    Windsor, G D; Trigwell

    1976-03-01

    Mycoplasma growth inhibiting antibody in rabbit anitsera was concentrated with a dry polyacrylamide gel. Discs prepared with such concentrated antisera inhibited only the homologous organism provided the antisera had been heated at 56 degrees C for 30 min, and when dried retained their potency during storage for over two years at 4 degrees C. PMID:1265363

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. Inhibition of miRNA maturation by peptide nucleic acids.

    PubMed

    Avitabile, Concetta; Fabbri, Enrica; Bianchi, Nicoletta; Gambari, Roberto; Romanelli, Alessandra

    2014-01-01

    Molecules able to interfere in miRNA genesis and function are potent tools to unravel maturation and processing pathways. Antisense oligonucleotides or analogs are actually employed for the inhibition of miRNA function. Here we illustrate how Peptide Nucleic Acids oligomers targeting pre-miRNA are exploited to inhibit miRNA maturation. PMID:24166311

  6. Orally administered FTS (salirasib) inhibits human pancreatic tumor growth in nude mice

    Microsoft Academic Search

    Roni Haklai; Galit Elad-Sfadia; Yaakov Egozi; Yoel Kloog

    2008-01-01

    Background  \\u000a S-trans,trans-farnesylthiosalicylic acid (salirasib, FTS) is a synthetic small molecule that acts as a potent Ras inhibitor. Salirasib\\u000a inhibits specifically both oncogenically activated Ras and growth factor receptor-mediated Ras activation, resulting in the\\u000a inhibition of Ras-dependent tumor growth. The objectives of this study were to develop a sensitive LC-MS\\/MS assay for determination\\u000a of FTS in plasma, to assess the bioavailabilty

  7. Inhibition of 13-cis retinoic acid-induced gene expression of homeobox B7 by thalidomide.

    PubMed

    Milanovi?, Dusan; Maier, Patrick; Lohr, Frank; Wenz, Frederik; Herskind, Carsten

    2007-09-15

    Thalidomide and 13-cis retinoic acid (RA) show anticancer effects as sole agents or in combination with other drugs. However, induction of homeobox (HOX) gene expression by 13-cis RA may contribute to tumor progression thereby potentially limiting its efficacy. The purpose was to test if thalidomide can inhibit 13-cis RA-induced HOXB7 expression and whether thalidomide may enhance the antiproliferative effect of 13-cis RA in U343MG glioblastoma cells. Quantitative real-time PCR showed significant inhibition of 13-cis RA-induced HOXB7 expression by thalidomide with IC(50) approximately 0.1-0.2 microg/ml when given simultaneously with 13-cis RA but not when administered 18 h later (p < 0.0001). 13-cis RA alone inhibited proliferation and colony formation in a concentration-dependent manner whereas growth inhibition by thalidomide alone at 5-100 microg/ml was constant at 80-90% of controls. At 10% serum concentration, growth inhibition by a combination of the 2 drugs was additive but at 1% serum, growth inhibition was synergistic. It is concluded that thalidomide inhibits the RA-induced HOXB7 expression in glioblastoma cells and that 13-cis RA/thalidomide combinations can in principle enhance cytotoxicity. The improved cell kill induced by thalidomide is attributed to downregulation of growth stimulatory factors induced by 13-cis RA. Implications for the modus operandi of thalidomide in embryogenesis are noted. PMID:17514648

  8. Growth of tobacco in short-day conditions leads to high starch, low sugars, altered diurnal changes in the Nia transcript and low nitrate reductase activity, and inhibition of amino acid synthesis.

    PubMed

    Matt, P; Schurr, U; Klein, D; Krapp, A; Stitt, M

    1998-12-01

    Diurnal changes in carbohydrates and nitrate reductase (NR) activity were compared in tobacco (Nicotiana tabacum. L.cv. Gatersleben) plants growing in a long (18 h light/6 h dark) and a short (6 h light/18 h dark) day growth regime, or after short-term changes in the light regime. In long-day-grown plants, source leaves contained high levels of sugars throughout the light and dark periods. In short-day-grown plants, levels of sucrose and reducing sugars were very low at the end of the night and, although they rose during the light period, remained much lower than in long days and declined to very low levels again by the middle of the night. Starch accumulated more rapidly in short-day-than long-day-grown plants. Starch was completely remobilised during the night in short days, but not in long days. A single short day/long night cycle sufficed to stimulate starch accumulation during the following light period. In long-day-grown plants, the Nia transcript level was high at the end of the night, decreased during the day, and recovered gradually during the night. In short-day-grown plants, the Nia transcript level was relatively low at the end of the night, decreased to very low levels at the end of the light period, increased to a marked maximum in the middle of the night, and decreased during the last 5 h of the dark period. In long-day-grown plants, NR activity in source leaves rose by 2- to 3-fold in the first part of the light period and decreased in the second part of the light period. In short-day-grown plants, NR activity was low at the end of the night, and only increased slightly after illumination. Dark inactivation of source-leaf NR was partially reversed in long-day-grown plants, but not in short day-grown plants. In both growth regimes, mutants with one instead of four functional copies of the Nia gene had a 60% reduction in maximum NR activity in the source leaves, compared to wild-type plants. The diurnal changes in NR activity were almost completely suppressed in the mutants in long days, whereas the mutants showed similar or slightly larger diurnal changes than wild-type plants in short days. When short-day-grown plants were transferred to long-day conditions for 3 d, NR activity and the diurnal changes in NR activity resembled those in long-day-grown plants. Phloem export from source leaves of short-day-grown plants was partially inhibited by applying a cold-girdle for one light and dark cycle. The resulting increase in leaf sugar was accompanied by an marked increase in the Nia transcript level and a 2-fold increase in NR activity at the end of the dark period. When wild-type plants were subjected to a single short day/long night cycle of increasing severity, NR activity in source leaves at the end of the night decreased when the endogenous sugars declined below about 3 mumol hexose (g FW)-1. In sink leaves in short-day conditions, sugars were higher and the light-induced rise in NR activity was much larger than in source leaves on the same plants. The source leaves of wild-type plants in short-day conditions contained very high levels of nitrate, very low levels of glutamine, low levels of total amino acids, and lower protein and chlorophyll, compared to long-day-grown plants. Plants grown in short days had relatively high levels of glutamate and aspartate, and extremely low levels of most of the minor amino acids in their source leaves at the end of the night. Illumination led to a decrease in glutamate and an increase in the minor amino acids. A single short day/long night cycle led to an increase in glutamate, and a large decrease in the minor acids at the end of the dark period, and reillumination led to a decrease in glutamate and an increase in the minor amino acids. It is proposed that sugar-mediated control of Nia expression and NR activity overrides regulation by nitrogenous compounds when sugars are in short supply, resulting in a severe inhibition of nitrate assimilation. It is also proposed that su PMID:9951717

  9. Polyhydroxycarboxylic acids as inhibitors of calcium oxalate crystal growth; Relation between inhibitory capacity and chemical structure

    NASA Astrophysics Data System (ADS)

    Grases, F.; Millan, A.; Garcia-Raso, A.

    1988-07-01

    The kinetics of crystal growth of calcium oxalate monohydrate seed crystals were investigated potentiometrically in the presence of several polyhydroxycarboxylic acids; etylenediaminetetraacetic acid, citric acid, isocitric acid, malic acid and succinic acid, and it was found that they inhibited crystal growth, except in the case of isocitric acid manifested no-effects. An apparent rate order of 2 in the presence of all the inhibitors, suggested a spiral growth mechanism. Application to a kinetic Langmuir-type model suggested that adsorption of the polyhydroxycarboxylic acids, at the active growth sites, is the cause of the reduction in the crystal growth rates. The inhibitory action of the different substances assayed was comparatively evaluated. Relations between chemical structure and inhibitory capacity were established.

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

    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.

  11. In Vitro Measurement of Pollen Tube Growth Inhibition

    PubMed Central

    Martin, Franklin W.

    1972-01-01

    A method for estimating inhibition of pollen tube growth was developed. Pollen is placed in straight lines on an agar surface where it responds uniformly and predictably to aqueous solutions of germination-inhibiting substances located in wells at the ends of the lines. A scale of ratings, roughly corresponding to serial, doubled concentrations of inhibiting substances, was devised. Water-soluble organic solvents are relatively noninhibitory, salts are variable, and metabolic inhibitors have strong inhibitory effects. Pollens differ in their susceptibility to inhibition and in their response to particular substances. PMID:16658085

  12. Root growth inhibition by NH4 in Arabidopsis is mediated

    E-print Network

    Kronzucker, Herbert J.

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

  13. Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase

    PubMed Central

    Zuther, E.; Johnson, J. J.; Haselkorn, R.; McLeod, R.; Gornicki, P.

    1999-01-01

    Aryloxyphenoxypropionates, inhibitors of the plastid acetyl-CoA carboxylase (ACC) of grasses, also inhibit Toxoplasma gondii ACC. Clodinafop, the most effective of the herbicides tested, inhibits growth of T. gondii in human fibroblasts by 70% at 10 ?M in 2 days and effectively eliminates the parasite in 2–4 days at 10–100 ?M. Clodinafop is not toxic to the host cell even at much higher concentrations. Parasite growth inhibition by different herbicides is correlated with their ability to inhibit ACC enzyme activity, suggesting that ACC is a target for these agents. Fragments of genes encoding the biotin carboxylase domain of multidomain ACCs of T. gondii, Plasmodium falciparum, Plasmodium knowlesi, and Cryptosporidium parvum were sequenced. One T. gondii ACC (ACC1) amino acid sequence clusters with P. falciparum ACC, P. knowlesi ACC, and the putative Cyclotella cryptica chloroplast ACC. Another sequence (ACC2) clusters with that of C. parvum ACC, probably the cytosolic form. PMID:10557330

  14. Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase.

    PubMed

    Zuther, E; Johnson, J J; Haselkorn, R; McLeod, R; Gornicki, P

    1999-11-01

    Aryloxyphenoxypropionates, inhibitors of the plastid acetyl-CoA carboxylase (ACC) of grasses, also inhibit Toxoplasma gondii ACC. Clodinafop, the most effective of the herbicides tested, inhibits growth of T. gondii in human fibroblasts by 70% at 10 microM in 2 days and effectively eliminates the parasite in 2-4 days at 10-100 microM. Clodinafop is not toxic to the host cell even at much higher concentrations. Parasite growth inhibition by different herbicides is correlated with their ability to inhibit ACC enzyme activity, suggesting that ACC is a target for these agents. Fragments of genes encoding the biotin carboxylase domain of multidomain ACCs of T. gondii, Plasmodium falciparum, Plasmodium knowlesi, and Cryptosporidium parvum were sequenced. One T. gondii ACC (ACC1) amino acid sequence clusters with P. falciparum ACC, P. knowlesi ACC, and the putative Cyclotella cryptica chloroplast ACC. Another sequence (ACC2) clusters with that of C. parvum ACC, probably the cytosolic form. PMID:10557330

  15. DASATINIB INHIBITS THE GROWTH OF MOLECULARLY HETEROGENEOUS MYELOID LEUKEMIAS

    PubMed Central

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

    2010-01-01

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

  16. In vitro cell growth inhibition by metallocene dichlorides.

    PubMed

    Köpf-Maier, P; Wagner, W; Köpf, H

    1981-01-01

    The in vitro growth-inhibiting potencies of titanocene dichloride (TDC), zirconocene dichloride (ZDC), hafnocene dichloride (HDC), vanadocene dichloride (VDC), and molybdocene dichloride (MDC) against Ehrlich ascites tumor (EAT) cells cultured in viro as permanently growing suspension cultures were determined. The most striking growth-suppression activity was detected for VDC. A VDC concentration as low as 5. 10(-6) mol/l effects a highly significant diminution of cell proliferation. TDC and MDC inhibit cellular growth only concentration of 5 . 10(-4) or 10(-3) mol/l, respectively, whereas ZDC and HDC, which are ineffective against EAT cells in vivo, require higher concentration levels. The growth inhibition is caused by a cytotoxic action of the metallocene dichlorides, as is demonstrated in the case of VDC and TDC by differentiation of live and dead EAT cells by means of the dye lissamine green. PMID:7261252

  17. Inhibition of Aluminum Oxyhydroxide Precipitation with Citric Acid

    E-print Network

    Aksay, Ilhan A.

    Inhibition of Aluminum Oxyhydroxide Precipitation with Citric Acid Daniel M. Dabbs, Usha 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

  18. Paradoxical Inhibition of Solid Tumor Cell Growth by bcl2

    Microsoft Academic Search

    Jennifer A. Pietenpol; Nickolas Papadopoulos; Sanford Markowitz; James K. V. Willson; Kenneth W. Kinzler; Bert Vogelstein

    The BCL2 gene product has been demonstratedto prevent apoptosis and provide a selective growth advantage to many cell types. We report an unexpected effect ofbcl2 expression on the in vitro growth of several solid tumor cell lines. Expressionof bcl2 in these cell lines resulted in growth inhibition similar to that seen with p53. In contrast, a COOH-terminal deletion mutant of

  19. Acid inhibition of CRA`s: A review

    SciTech Connect

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

    1994-12-31

    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.

  20. Inhibition of Gibberellic Acid-induced Elongation in Avena Stem Segments by a Substituted Pyrimidine.

    PubMed

    Montague, M J

    1975-08-01

    Avena stem segments, which respond with high amplitude, specificity, and sensitivity to gibberellic acid, were used to study the inhibition of gibberellin-induced elongation by the growth retardant alpha-cyclopropyl-alpha-(4-methoxyphenyl)-5-pyrimidine methanol (EL-531). It was found that EL-531 strongly inhibits gibberellic acid-induced elongation in this system at a concentration of 1 mm. From a double-reciprocal plot of elongation and gibberellic acid concentration, it seems that EL-531 and gibberellic acid do not compete reversibly for the same site of action. Also, because EL-531 effectively inhibits elongation in internodal tissue dissected away from the node and leaf sheath, it cannot be acting primarily by inhibiting the synthesis or transport of the leaf sheath factor(s). Because EL-531 causes lateral expansion of the stem segments as well as increased diameters of epidermal cells, in a manner very similar to the effects of colchicine, it is suggested that EL-531 inhibits gibberellic acid-induced elongation by somehow interfering with the orientation of the products of cell wall synthesis. PMID:16659267

  1. Oligodendrocytes Arrest Neurite Growth by Contact Inhibition

    Microsoft Academic Search

    Christine Bandtlow; Thomas Zachleder; Martin E. Schwab

    1990-01-01

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

  2. Spectroscopic analysis of urinary calculi and inhibition of their growth

    NASA Astrophysics Data System (ADS)

    Manciu, Felicia; Durrer, William; Govani, Jayesh; Reza, Layra; Pinales, Luis

    2009-10-01

    We present here a study of kidney stone formation and growth inhibition based on a traditional medicine approach with Aquatica Lour (RAL) herbal extracts. Kidney stone material systems were synthesized in vitro using a simplified single diffusion gel growth technique. With the objective of revealing the mechanism of inhibition of calculi formation by RAL extracts, samples prepared without the presence of extract, and with the presence of extract, were analyzed using Raman, photoluminescence, and XPS. The unexpected presence of Zn revealed by XPS in a sample prepared with RAL provides an explanation for the inhibition process, and also explains the dramatic reflectance of incident light observed in attempts to obtain infrared transmission data. Raman data are consistent with the binding of the inhibitor to the oxygen of the kidney stone. Photoluminescence data corroborate with the other results to provide additional evidence of Zn-related inhibition.

  3. 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...

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

    SciTech Connect

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

    2014-01-03

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

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

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

    SciTech Connect

    Iraci, L.T.; Middlebrook, A.M.; Wilson, M.A.; Tolbert, M.A. (Univ. of Colorado, Boulder, CO (United States))

    1994-05-15

    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 probe the phase of the sulfuric acid and to identify the HNO[sub 3]/H[sub 2]O films that condensed. Nitric acid trihydrate (NAT) was observed to grow on crystalline sulfuric acid tetrahydrate (SAT) films. NAT also condensed in/on supercooled H[sub 2]SO[sub 4] 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.

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

    SciTech Connect

    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

    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.

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

    PubMed Central

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

    2005-01-01

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

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

    PubMed

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

    2005-02-01

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

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

    SciTech Connect

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

    2012-11-16

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

  11. Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts.

    PubMed

    Guo, Lei; Xiao, Yongsheng; Wang, Yinsheng

    2014-05-15

    Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ~6500 unique proteins quantified, ~300 displayed significant changes in expression after exposure with 2 ?M MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. PMID:24625837

  12. Soil acidity and its relationship to root growth in declining forest stands in Germany

    Microsoft Academic Search

    E. Matzne; D. Murach; H. Fortmann

    1986-01-01

    Ingrowth core studies were used to investigate the influence of 3 different soils on root growth of Norway spruce in two stands in Northwest Germany. Root growth was significantly inhibited by the acid soil treatment. The amount of roots which had grown into the limed ingrowth cores were much higher and the percentage of dead roots was less when compared

  13. A model for multiproduct-inhibited growth of Enterobacter aerogenes in 2,3-butanediol fermentation

    Microsoft Academic Search

    An-Ping Zeng; Wolf-Dieter Deckwer

    1991-01-01

    Ethanol is identified as a strongly inhibitory metabolite in addition to acetic acid and 2,3-butanediol in 2,3-butanediol production by Enterobacter aerogenes. A model is proposed to describe the multiproduct-inhibited growth of E. aerogenes in 2,3-butanediol fermentation. The model is verified with data from anaerobic and microaerobic continuous culture. On the basis of this model the difference in biomass production and

  14. A Peptide with Three Hyaluronan Binding Motifs Inhibits Tumor Growth and Induces Apoptosis1

    Microsoft Academic Search

    Xue-Ming Xu; Yixin Chen; Jinguo Chen; Shanmin Yang; Feng Gao; Charles B. Underhill; Karen Creswell; Lurong Zhang

    2003-01-01

    A number of hyaluronan (HA) binding proteins such as soluble CD44, receptor for hyaluronan-mediated motility (RHAMM), and metastatin inhibit tumor growth and metastasis. To determine whether the HA binding motif is the element responsible for the antitumor effect of this family of proteins, we examined the biological activity of a 42-amino acid peptide (designated as BH-P) that contains three HA

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

    PubMed Central

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

    2013-01-01

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

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

    Microsoft Academic Search

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

    2008-01-01

    SUMMARY Neurotrophic small molecules have the potential to aid in the treatment of neuronal injury and neurode- generative diseases. The natural product fellutamide B, originally isolated from Penicillium fellutanum, potently induces nerve growth factor (NGF) release from fibroblasts and glial-derived cells, although the mechanism for this neurotrophic activity has not been elucidated. Here, we report that fellutamide B potently inhibits

  17. Phytotoxicity of nanoparticles: Inhibition of seed germination and root growth

    Microsoft Academic Search

    Daohui Lin; Baoshan Xing

    2007-01-01

    Plants need to be included to develop a comprehensive toxicity profile for nanoparticles. Effects of five types of nanoparticles (multi-walled carbon nanotube, aluminum, alumina, zinc, and zinc oxide) on seed germination and root growth of six higher plant species (radish, rape, ryegrass, lettuce, corn, and cucumber) were investigated. Seed germination was not affected except for the inhibition of nanoscale zinc

  18. Betuligenol derivative with growth inhibition and antifeedant activity.

    PubMed

    Chattopadhyay, Sunil K; Srivastava, Sachin; Sashidhara, Koneni V; Tripathi, Arun K; Bhattacharya, Asish K; Negi, Arvind S

    2004-04-01

    The title chiral amine, 3-(4-methoxyphenyl)-1-methylpropylamine 5 has been synthesized from naturally abundant betuligenol 1 in three steps and also in good yield. Furthermore, the versatile intermediate 3 could be manipulated for the preparation of chiral disulphide 7. The amine derivative 5 prepared from (-)-betuligenol showed significant growth inhibition and antifeedant activity. PMID:15026059

  19. Reversible inhibition of calcium oxalate monohydrate growth by an osteopontin phosphopeptide.

    PubMed

    Nene, Shailesh S; Hunter, Graeme K; Goldberg, Harvey A; Hutter, Jeffrey L

    2013-05-28

    Calcium oxalate, primarily as calcium oxalate monohydrate (COM), is the primary constituent of most kidney stones. Certain proteins, such as osteopontin (OPN), inhibit stone formation. The complexity of stone formation and the effects of urinary proteins at various stages of the process make it hard to predict the exact physiological roles of these proteins in growth inhibition. The inhibition of crystallization due to adsorbed impurities is usually explained in terms of a model proposed in 1958 by Cabrera and Vermilyea. In this model, impurities adsorb to growth faces and pin growth steps, forcing them to curve, thus impeding their progress via the Gibbs-Thomson effect. To determine the role of OPN in the biomineralization of kidney stones, crystal growth on the {010} face of COM was examined in real time with atomic force microscopy in the presence of a synthetic peptide corresponding to amino acids 65-80 (hereafter referred to as pOPAR) of rat bone OPN. We observed clear changes in the morphology of the growth-step structure and a decrease in step velocity upon addition of pOPAR, which suggest adsorption of inhibitors on the {010} growth hillocks. Experiments in which pOPAR was replaced in the growth cell by a supersaturated solution showed that COM hillocks are able to fully recover to their preinhibited state. Our results suggest that recovery occurs through incorporation of the peptide into the growing crystal, rather than by, e.g., desorption from the growth face. This work provides new insights into the mechanism by which crystal growth is inhibited by adsorbants, with important implications for the design of therapeutic agents for kidney stone disease and other forms of pathological calcification. PMID:23611580

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

    PubMed Central

    2013-01-01

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

  1. [Growth inhibition and mechanism of cetyltrimethyl ammonium chloride on Chlorella vulgaris].

    PubMed

    Xu, Yin; Ge, Fei; Tao, Neng-Guo; Zhu, Run-Liang; Wang, Na

    2009-06-15

    Growth inhibition of cetyltrimethyl ammonium chloride (CTAC), a cationic surfactants, on Chlorella vulgaris was investigated at batch culture in laboratory. Furthermore, the corresponding mechanisms were studied by the determination of absorption capacity, Zeta potential, activity of acid phosphatase and ultrastructure of algae. Results show that the growth inhibition by CATC is enhanced with its concentration increasing from 0.1 mg/L to 1 mg/L, and 96 h-EC50 of CTAC is 0.18 mg/L. In the presence of 0.3 mg/L CTAC in 8 d, the inhibition efficiency of biomass reaches 70.7%. Meanwhile, the absorption of nitrogen and iron is inhibited 83.9% and 86.2% respectively with Zeta potential of algae cell increasing from -12.5 mV to -6.7 mV. Furthermore, the relative activity of acid phosphatase declines to 23.1% at the same time. Plasmolysis, distortion of pyrenoid and swelling of lysosome is observed in the cell. Above phenomena indicates that CTAC increases the Zeta potential of algae cell and thus inhibites the absorption of nitrogen and iron. In addition, CTAC may affect the metabolism of phosphorus and change the ultrastructure of algae cell. PMID:19662866

  2. Inhibition of mycotoxin-producing Aspergillus nomius vsc 23 by lactic acid bacteria and Saccharomyces cerevisiae.

    PubMed

    Muñoz, R; Arena, M E; Silva, J; González, S N

    2010-10-01

    The effect of different fermenting microorganisms on growth of a mycotoxin- producing Aspergillus nomius was assayed. Two lactic acid bacteria, Lactobacillus fermentum and Lactobacillus rhamnosus, and Saccharomyces cerevisiae, all of which are widely used in fermentation and preservation of food, were assayed on their fungus inhibitory properties. Assays were carried out by simultaneous inoculation of one of the possible inhibiting microorganisms and the fungus or subsequent inoculation of one of the microorganisms followed by the fungus. All three microorganisms assayed showed growth inhibition of the mycotoxin-producing Aspergillus strain. L. rhamnosus O236, isolated from sheep milk and selected for its technological properties, showed highest fungal inhibition of the microorganisms assayed. The use of antifungal LAB with excellent technological properties rather than chemical preservatives would enable the food industry to produce organic food without addition of chemical substances. PMID:24031582

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

    PubMed Central

    2014-01-01

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

  4. Growth modification of seeded calcite using carboxylic acids: atomistic simulations.

    PubMed

    Aschauer, Ulrich; Spagnoli, Dino; Bowen, Paul; Parker, Stephen C

    2010-06-01

    Molecular dynamics simulations were used to investigate possible explanations for experimentally observed differences in the growth modification of calcite particles by two organic additives, polyacrylic acid (PAA) and polyaspartic acid (p-ASP). The more rigid backbone of p-ASP was found to inhibit the formation of stable complexes with counter-ions in solution, resulting in a higher availability of p-ASP compared to PAA for surface adsorption. Furthermore the presence of nitrogen on the p-ASP backbone yields favorable electrostatic interactions with the surface, resulting in negative adsorption energies, in an upright (brush conformation). This leads to a more rapid binding and longer residence times at calcite surfaces compared to PAA, which adsorbed in a flat (pancake) configuration with positive adsorption energies. The PAA adsorption occurring despite this positive energy difference can be attributed to the disruption of the ordered water layer seen in the simulations and hence a significant entropic contribution to the adsorption free energy. These findings help explain the stronger inhibiting effect on calcite growth observed by p-ASP compared to PAA and can be used as guidelines in the design of additives leading to even more marked growth modifying effects. PMID:20304410

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

    PubMed

    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

    2014-12-15

    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

  6. Inhibition of angiogenesis by aurintricarboxylic acid.

    PubMed

    Gagliardi, A R; Collins, D C

    1994-01-01

    The triphenylmethane derivative, aurintricarboxylic acid (ATA), but not aurin, is a potent inhibitor of angiogenesis in the chick chorioallantoic membrane. ATA alone showed potent anti-angiogenic activity in a dose-related manner. The presence of heparin or bFGF decreased the anti-angiogenic activity of ATA. ATA also potentiated the anti-angiogenic activity of the angiostatic steroids, cortisol-21-phosphate, 17 alpha-hydroxyprogesterone, tetrahydrocortisol, tetrahydrocortexolone and medroxyprogesterone acetate. These results indicate that ATA is a potent inhibitor of angiogenesis and potentiates the activity of the angiostatic steroids. These novel findings with this negatively charged, nonsulfated aromatic compound may be the basis for important new therapeutic approaches for the diseases of neovascularization. PMID:7517120

  7. Inhibition Enzyme Sensor for Nicotine, Nicotinamide and Nicotinic Acid Determination

    NASA Astrophysics Data System (ADS)

    Campanella, L.; Cocco, R.; Favero, G.; Sammartino, M. P.; Tomassetti, M.

    2000-12-01

    Nicotine, nicotinic acid and nicotinamide were tested in pharmaceutical products using an inhibition enzyme sensor consisting of a hydrogen peroxide amperometric electrode coupled to a functionalised nylon membrane chemically bonding the enzymes butyrylcholinesterase and choline oxidase; a butyrylcholine standard solution in glycine buffer acted as substrate.

  8. Elevated serum free fatty acid concentrations inhibit T lymphocyte signaling

    Microsoft Academic Search

    THOMAS M. STULNIG; MARKUS BERGER; MICHAEL RODEN; HARALD STINGL; DANIEL RAEDERSTORFF; WERNER WALDHAUSL

    Unbound cis-unsaturated free (i.e., nonesterified) fatty acids (FFA) inhibit T lymphocyte activation in vitro and therefore may exert immuno- suppressive effects. However, in blood serum the major proportion of FFA is tightly bound to albumin, whereas unbound FFA are hardly detectable. Since serum FFA elevation occurs under pathological con- ditions like insulin resistance or cancer, which are often associated with

  9. Reversible inhibition of intercellular junctional communication by glycyrrhetinic acid.

    PubMed

    Davidson, J S; Baumgarten, I M; Harley, E H

    1986-01-14

    Intercellular gap-junctional communication was measured using metabolic co-operation in co-cultures of argininosuccinate synthetase-deficient and argininosuccinate lyase-deficient human fibroblasts. 18-alpha-glycyrrhetinic acid (AGA) was found to inhibit communication by more than 95% at concentrations as low as 2 microM. Concentrations up to 100 microM were not cytotoxic over a period of 2 hours. Communication inhibition was of rapid onset and was readily reversible. Communication remained continuously yet reversibly blocked in cells cultured in the presence of AGA for 20 days. The related compounds 18-beta-glycyrrhetinic acid and carbenoxolone also caused communication inhibition. The effect is probably not mediated via mineralocorticoid or glucocorticoid receptors since aldosterone and glucocorticoids had no effect on communication. AGA thus has properties of a useful inhibitor in the study of intercellular junctional communication. PMID:3947327

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

    SciTech Connect

    Nonami, Hiroshi [Ehime Univ., Matsuyama (Japan); Wu, Yajun; Boyer, J.S. [Univ. of Delaware, Lewes, DE (United States)

    1997-06-01

    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 growth increased when the roots were pressurized and it reverted to the previous rate when the pressure was released. The pressure around the roots was perceived as an increased turgor in the stem in small cells next to the xylem, but not in outlying cortical cells. This local effect implied that water transport was impeded by the small cells. The diffusivity for water was much less in the small cells than in the outlying cells. The small cells thus were a barrier that caused the growth-induced potential difference to be large during rapid growth, but to reverse locally during the early part of a water deficit. Such a barrier may be a frequent property of meristems. Because stem growth responded to the pressure-induced recovery of the potential difference across this barrier, we conclude that a decrease in the growth-induced potential difference was a primary cause of the inhibition.

  11. Effects of acidity on tree pollen germination and tube growth

    SciTech Connect

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

    1985-01-01

    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.

  12. Effect of Phosphate and pH on Streptococcus mutans Acid Production and Growth

    Microsoft Academic Search

    Stanley L. Handelman; Gerald H. Kreinces

    1973-01-01

    The effect of phosphate concentration and the initial pH of bacteriologic media on acid production and bacterial growth of Streptococcus mutans was studied. There was an inhibition of acid production and bacterial growth with an increase in concentrations of phosphate, particularly when the initial pH of the media was 8.0. At a pH of 6.5 the effect was minimal.

  13. Gradient Microfluidics Enables Rapid Bacterial Growth Inhibition Testing

    PubMed Central

    2014-01-01

    Bacterial growth inhibition tests have become a standard measure of the adverse effects of inhibitors for a wide range of applications, such as toxicity testing in the medical and environmental sciences. However, conventional well-plate formats for these tests are laborious and provide limited information (often being restricted to an end-point assay). In this study, we have developed a microfluidic system that enables fast quantification of the effect of an inhibitor on bacteria growth and survival, within a single experiment. This format offers a unique combination of advantages, including long-term continuous flow culture, generation of concentration gradients, and single cell morphology tracking. Using Escherichia coli and the inhibitor amoxicillin as one model system, we show excellent agreement between an on-chip single cell-based assay and conventional methods to obtain quantitative measures of antibiotic inhibition (for example, minimum inhibition concentration). Furthermore, we show that our methods can provide additional information, over and above that of the standard well-plate assay, including kinetic information on growth inhibition and measurements of bacterial morphological dynamics over a wide range of inhibitor concentrations. Finally, using a second model system, we show that this chip-based systems does not require the bacteria to be labeled and is well suited for the study of naturally occurring species. We illustrate this using Nitrosomonas europaea, an environmentally important bacteria, and show that the chip system can lead to a significant reduction in the period required for growth and inhibition measurements (<4 days, compared to weeks in a culture flask). PMID:24548044

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

    E-print Network

    Paris-Sud XI, Université de

    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

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

    SciTech Connect

    Zaldivar, J.; Ingram, L.O.

    1999-07-01

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

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

    Microsoft Academic Search

    A. Santi; T. June

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

  17. Identification of metabolites of the antitumor agent d-limonene capable of inhibiting protein isoprenylation and cell growth.

    PubMed

    Crowell, P L; Lin, S; Vedejs, E; Gould, M N

    1992-01-01

    Limonene has been shown to be an effective, nontoxic chemopreventive and chemotherapeutic agent in chemically induced rat mammary-cancer models. The present study characterized circulating metabolites of limonene in female rats and determined their effects on cell growth. Metabolism of limonene was analyzed in plasma extracts by gas chromatography. Rapid conversion of limonene to two major metabolites was detected. These metabolites comprised more than 80% of the circulating limonene-derived material at 1 h after administration and thereafter, whereas limonene itself accounted for only 15%. The metabolites were characterized by mass spectroscopy and infrared spectroscopy. The probable structures were synthesized, and identities were confirmed by comparison of retention times and mass spectra. The two major circulating metabolites of limonene were found to be perillic acid and dihydroperillic acid. We have previously reported that limonene, perillic acid, and dihydroperillic acid inhibit the posttranslational isoprenylation of p21ras and other 21- to 26-kDa cell-growth-associated proteins in NIH3T3 cells and in mammary epithelial cells. In the present study, perillic acid was found to inhibit cell growth in a dose-dependent manner. Thus, perillic acid and dihydroperillic acid, the two major circulating metabolites of limonene in the rat, are more potent inhibitors of protein isoprenylation than is limonene, and perillic acid is also a more potent inhibitor of cell growth. These data raise the possibility that the antitumor effects of limonene in vivo may be mediated via perillic acid and, perhaps, other metabolites. PMID:1464157

  18. Diverse mechanisms of growth inhibition by luteolin, resveratrol, and quercetin in MIA PaCa-2 cells: a comparative glucose tracer study with the fatty acid synthase inhibitor C75

    PubMed Central

    Li, Luyi; Chen, Monica; Lagunero, F. Tracy; Go, Vay Liang W.; Boros, Laszlo G.

    2011-01-01

    The rationale of this dose matching/dose escalating study was to compare a panel of flavonoids—luteolin, resveratrol, and quercetin—against the metabolite flux-controlling properties of a synthetic targeted fatty acid synthase inhibitor drug C75 on multiple macromolecule synthesis pathways in pancreatic tumor cells using [1,2-13C2]-d-glucose as the single precursor metabolic tracer. MIA PaCa-2 pancreatic adenocarcinoma cells were cultured for 48 h in the presence of 0.1% DMSO (control), or 50 or 100 ?M of each test compound, while intracellular glycogen, RNA ribose, palmitate and cholesterol as well as extra cellular 13CO2, lactate and glutamate production patterns were measured using gas chromatography/mass spectrometry (GC/MS) and stable isotope-based dynamic metabolic profiling (SiDMAP). The use of 50% [1,2-13C2]-d-glucose as tracer resulted in an average of 24 excess 13CO2 molecules for each 1,000 CO2 molecule in the culture media, which was decreased by 29 and 33% (P < 0.01) with 100 ?M C75 and luteolin treatments, respectively. Extracellular tracer glucose-derived 13C-labeled lactate fractions (?m) were between 45.52 and 47.49% in all cultures with a molar ratio of 2.47% M + 1/?m lactate produced indirectly by direct oxidation of glucose in the pentose cycle in control cultures; treatment with 100 ?M C75 and luteolin decreased this figure to 1.80 and 1.67%. The tracer glucose-derived 13C labeled fraction (?m) of ribonucleotide ribose was 34.73% in controls, which was decreased to 20.58 and 8.45% with C75, 16.15 and 6.86% with luteolin, 27.66 and 19.25% with resveratrol, and 30.09 and 25.67% with quercetin, respectively. Luteolin effectively decreased nucleotide precursor synthesis pentose cycle flux primarily via the oxidative branch, where we observed a 41.74% flux (M + 1/?m) in control cells, in comparison with only a 37.19%, 32.74%, or a 26.57%, 25.47% M + 1/?m flux (P < 0.001) after 50 or 100 ?M C75 or luteolin treatment. Intracellular de novo fatty acid palmitate (C16:0) synthesis was severely and equally blocked by C75 and luteolin treatments indicated by the 5.49% (control), 2.29 or 2.47% (C75) and 2.21 or 2.73% (luteolin) tracer glucose-derived 13C-labeled fractions, respectively. On the other hand there was a significant 192 and 159% (P < 0.001), and a 103 and 117% (P < 0.01) increase in tracer glucose-derived cholesterol after C75 or luteolin treatment. Only resveratrol and quercetin at 100 ?M inhibited tracer glucose-derived glycogen labeling (?m) and turnover by 34.8 and 23.8%, respectively. The flavonoid luteolin possesses equal efficacy to inhibit fatty acid palmitate de novo synthesis as well as nucleotide RNA ribose turnover via the oxidative branch of the pentose cycle in comparison with the targeted fatty acid synthase inhibitor synthetic compound C75. Luteolin is also effective in stringently controlling glucose entry and anaplerosis in the TCA cycle, while it promotes less glucose flux towards cholesterol synthesis than that of C75. In contrast, quercetin and resveratrol inhibit glycogen synthesis and turnover as their underlying mechanism of controlling tumor cell proliferation. Therefore the flavonoid luteolin controls fatty and nucleic acid syntheses as well as energy production with pharmacological strength, which can be explored as a non-toxic natural treatment modality for pancreatic cancer. PMID:22754424

  19. Salicylic acid inhibits jasmonic acid-induced resistance of Arabidopsis thaliana to Spodoptera exigua.

    PubMed

    Cipollini, D; Enright, S; Traw, M B; Bergelson, J

    2004-06-01

    The role of salicylic acid (SA) in plant responses to pathogens has been well documented, but its direct and indirect effects on plant responses to insects are not so well understood. We examined the effects of SA, alone and in combination with jasmonic acid (JA), on the performance of the generalist herbivore, Spodoptera exigua, in wild-type and mutant Arabidopsis thaliana genotypes that varied genetically in their ability to mount SA- and JA-mediated defence responses. In one experiment, growth of S. exigua larvae was highest on the Wassilewskija wild-type, intermediate on the Columbia wild-type and the JA-deficient fad mutant, and lowest on the nim1-1 and jar1-mutants, which are defective in the SA and JA pathways, respectively. Activity of guaiacol peroxidase, polyphenoloxidase, n-acetylglucosaminidase, and trypsin inhibitor varied by genotype but did not correlate with insect performance. SA treatment increased growth of S. exigua larvae by approximately 35% over all genotypes, but had no discernable effect on activities of the four defence proteins. In a second experiment, growth of S. exigua was highest across treatments on the cep1 mutant, a constitutive expressor of high SA levels and systemic acquired resistance, and lowest on the fad mutant, which is JA-deficient. JA treatment generally increased activity of all four defence proteins, increased total glucosinolate levels and reduced insect growth by approximately 25% over all genotypes. SA generally inhibited expression of JA-induced resistance to S. exigua when both hormones were applied simultaneously. Across genotypes and treatments, larval mass was negatively correlated with the activity of trypsin inhibitor and polyphenoloxidase and with total glucosinolate levels, and insect damage was negatively correlated with the activity of polyphenoloxidase. SA had little effect on the induction of defence protein activity by JA. However, SA attenuated the induction of glucosinolates by JA and therefore may explain better the interactive effects of SA and JA on insect performance. This study illustrates that direct and indirect cross-effects of SA on resistance to S. exigua can occur in A. thaliana. Effects of SA may be mediated through effects on plant defence chemistry or other aspects of the suitability of foliage for insect feeding and growth. PMID:15140107

  20. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  2. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    PubMed

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

    2012-01-01

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

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

    Microsoft Academic Search

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

    2007-01-01

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

  4. Hydroxyapatite-binding peptides for bone growth and inhibition

    DOEpatents

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

    2011-09-20

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

  5. Growth Inhibition of Pathogenic Bacteria by Sulfonylurea Herbicides

    PubMed Central

    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

    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

  6. Fucoidan inhibits the growth of hepatocellular carcinoma independent of angiogenesis.

    PubMed

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

    2013-01-01

    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

  7. Modeling and simulation of lactic acid fermentation with inhibition effects of lactic acid and glucose

    Microsoft Academic Search

    Jian-qiang Lin; Sang-Mok Lee; Yoon-Mo Koo

    2004-01-01

    An unstructured mathematical model for lactic acid fermentation was developed. This model was able to predict the inhibition\\u000a effects of lactic acid and glucose and was confirmed to be valid with various initial concentrations of lactic acid and glucose.\\u000a Simulation of energy production was made using this mathematical model, and the relationship between the kinetics of energy\\u000a metabolism and lactic

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

    Microsoft Academic Search

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

    2000-01-01

    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

  9. D-Amino acids inhibit initial bacterial Adhesion: Thermodynamic evidence.

    PubMed

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

    2015-04-01

    Bacterial biofilms are structured communities of cells enclosed in a self-produced hydrated polymeric matrix that can adhere to inert or living surfaces. D-Amino acids were previously identified as self-produced compounds that mediate biofilm disassembly by causing the release of the protein component of the polymeric matrix. However, whether exogenous D-amino acids could inhibit initial bacterial adhesion is still unknown. Here, the effect of the exogenous amino acid D-tyrosine on initial bacterial adhesion was determined by combined use of chemical analysis, force spectroscopic measurement, and theoretical predictions. The surface thermodynamic theory demonstrated that the total interaction energy increased with more D-tyrosine, and the contribution of Lewis acid-base interactions relative to the change in the total interaction energy was much greater than the overall nonspecific interactions. Finally, atomic force microscopy analysis implied that the hydrogen bond numbers and adhesion forces decreased with the increase in D-tyrosine concentrations. D-Tyrosine contributed to the repulsive nature of the cell and ultimately led to the inhibition of bacterial adhesion. This study provides a new way to regulate biofilm formation by manipulating the contents of D-amino acids in natural or engineered systems. Biotechnol. Bioeng. 2015;112: 696-704. © 2014 Wiley Periodicals, Inc. PMID:25333717

  10. Inhibitive efficiency of sulphathiazole for aluminum corrosion in trichloroacetic acid

    Microsoft Academic Search

    P. S. Desai; R. T. Vashi

    2011-01-01

    Purpose – The purpose of this paper is to investigate the effect that different concentrations of the inhibitor sulphathiazole have on the corrosion of aluminum in 0.01, 0.05 and 0.10 M trichloroacetic acid (TCA), and to elucidate the mechanisms of inhibition for this system. Design\\/methodology\\/approach – Gravimetric measurements and galvanostatic polarization were used to investigate the effect of sulphathiazole on

  11. Understanding viral neuraminidase inhibition by substituted difluorosialic acids.

    PubMed

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

    2015-02-18

    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

  12. Studies of the effect of gibberellic acid on algal growth.

    NASA Technical Reports Server (NTRS)

    Evans, W. K.; Sorokin, C.

    1971-01-01

    The effect of gibberellic acid on exponential growth rate of four strains of Chlorella was investigated under variety of experimental conditions. In concentrations from 10 ppm to 100 ppm, gibberellic acid was shown to have no effect on Chlorella growth. In concentration of 200 ppm, gibberellic acid exerted some unfavorable effect on algal growth.

  13. Ent-11?-Hydroxy-15-oxo-kaur-16-en-19-oic-acid Inhibits Growth of Human Lung Cancer A549 Cells by Arresting Cell Cycle and Triggering Apoptosis

    PubMed Central

    Li, Li; Chen, George G; Lu, Ying-nian; Liu, Yi; Wu, Ke-feng; Gong, Xian-ling; Gou, Zhan-ping; Li, Ming-yue

    2012-01-01

    Objective To examine the apoptotic effect of ent-11?-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), a compound isolated from Pteris semipinnata L (PsL), in human lung cancer A549 cells. Methods A549 cells were treated with 5F (0–80 ?g/ml) for different time periods. Cytotoxicity was examined using a MTT method. Cell cycle was examined using propidium iodide staining. Apoptosis was examined using Hoechst 33258 staining, enzyme-linked immunosorbent assay (ELISA) and caspase-3 activity analysis. Expression of representative apoptosis-related proteins was evaluated by Western blot analysis. Reactive oxygen species (ROS) level was measured using standard protocols. Potential interaction of 5F with cisplatin was also examined. Results 5F inhibited the proliferation of A549 cells in a concentration- and time-dependent manner. 5F increased the accumulation of cells in sub-G1 phase and arrested the cells in the G2 phase. Exposure to 5F induced morphological changes and DNA fragmentation that are characteristic of apoptosis. The expression of p21 was increased. 5F exposure also increased Bax expression, release of cytochrome c and apoptosis inducing factor (AIF), and activation of caspase-3. 5F significantly sensitized the cells to cisplatin toxicity. Interestingly, treatment with 5F did not increase ROS, but reduced ROS production induced by cisplatin. Conclusion 5F could inhibit the proliferation of A549 cells by arresting the cells in G2 phase and by inducing mitochondrial-mediated apoptosis. PMID:23358391

  14. Effect of growth hormone-release inhibiting hormone on hormones stimulating exocrine pancreatic secretion.

    PubMed Central

    Konturek, S J; Tasler, J; Obtulowicz, W; Coy, D H; Schally, A V

    1976-01-01

    The nature and extent of growth hormone-release inhibiting hormone (GH-RIH, somatostatin)-induced inhibition of pancreatic secretion of bicarbonate and protein, an index of enzyme secretion, were studied by administration of exogenous secretin or cholecystokinin (CCK) and of a number of stimulants for endogenous release of these hormones in fasted pancreatic fistula dogs with and without an infusion of GH-RIH. The results of this study show that GH-RIH inhibits the pancreatic fluid and bicarbonate secretion induced by duodenal acidification and exogenous secretion. The kinetic analysis shows that the interaction between GH-RIH and secretin affecting pancreatic bicarbonate secretion possesses the characteristics of competitive inhibition. GH-RIH does not change the pancreatic protein response to exogenous CCK, but profoundly inhibits pancreatic response to a variety of the endogenous stimulants of CCK release, including duodenal perfusion of sodium oleate, amino acid mixture, or feeding of a peptone meal. We conclude that GH-RIH is a very potent inhibitor of the endogenous release of CCK from the intestinal mucosa and inhibits competitively the action of secretin but not CCK on the exocrine pancreatic secretion. PMID:932201

  15. Antigen 85C inhibition restricts Mycobacterium tuberculosis growth through disruption of cord factor biosynthesis.

    PubMed

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

    2012-04-01

    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

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

    PubMed Central

    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

    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

  17. Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cells

    Microsoft Academic Search

    Wojciech Rzeski; Andrzej Stepulak; Marek Szyma?ski; Marco Sifringer; Józef Kaczor; Katarzyna Wejksza; Barbara Zdzisi?ska; Martyna Kandefer-Szersze?

    2006-01-01

    Betulinic acid (BA) is a pentacyclic triterpene found in many plant species, among others in the bark of white birch Betula alba. BA was reported to display a wide range of biological effects, including antiviral, antiparasitic, antibacterial and anti-inflammatory activities, and in particular to inhibit growth of cancer cells. The aim of the study was further in vitro characterization of

  18. Inhibition of intracranial glioma growth by endometrial regenerative cells.

    PubMed

    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

    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

  19. Inhibition of spoilage and food-borne pathogens by lactic acid bacteria isolated from fermenting tef (Eragrostis tef) dough.

    PubMed

    Nigatu, A; Gashe, B A

    1994-10-01

    A study was carried out at the Department of Biology, Addis Abeba University, in 1991 to determine the inhibitory potential of fermenting tef and the lactic acid bacteria isolated from fermenting tef dough on Salmonella spp., Pseudomonas aeruginosa, Klebsiella spp., Bacillus cereus and Staphylococcus aureus. The test bacteria grew in the fermenting tef uptill 30 hr or till the pH dropped to 4.7. Thereafter, growth was inhibited and decreases in population were apparent. The results showed that the spent media from all of the four lactic acid bacterial isolates, namely, Lactobacillus spp., Pediococcus spp., Leuconostoc spp. and Streptococcus spp. inhibited the test bacteria. Acidity on its own was not responsible for the inhibition of the test bacteria. The spent medium from Streptococcus spp. showed the best inhibitory activity amongst the lactic acid bacteria. PMID:7835350

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2012-12-01

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

  2. [Growth inhibition effect of immobilized pectinase on Microcystis aeruginosa].

    PubMed

    Shen, Qing-Qing; Peng, Qian; Lai, Yong-Hong; Ji, Kai-Yan; Han, Xiu-Lin

    2012-12-01

    To confirm the growth inhibition effect of immobilized pectinase on algae, co-cultivation method was used to investigate the effect of immobilized pectinase on the growth of Microcystis aeruginosa. After co-cultivation, the damage status of the algae was observed through electron microscope, and the effect of immobilized pectase on the physiological and biochemical characteristics of the algae was also measured. The results showed that the algae and immobilized pectase co-cultivated solution etiolated distinctly on the third day and there was a significantly positive correlation between the extent of etiolation and the dosage as well as the treating time of the immobilized pectinase. Under electron microscope, plasmolysis was found in the slightly damaged cells, and the cell surface of these cells was rough, uneven and irregular; the severely damaged cells were collapsed or disintegrated completely. The algal yield and the chlorophyll a content decreased significantly with the increase of the treating time. The measurement of the malondiadehyde (MDA) value showed that the antioxidation system of the treated algal cells was destroyed, and their membrane lipid was severely peroxidated. The study indicated that the immobilized pectinase could efficiently inhibit the growth of M. aeruginosa, and the inhibitory rate reached up to 96%. PMID:23379158

  3. In vitro repolarized tumor macrophages inhibit gastric tumor growth.

    PubMed

    Liu, Hao; Wu, Xiaolin; Wang, Shanmei; Deng, Wei; Zan, Lipin; Yu, Shuangjiang

    2013-01-01

    Gastric cancer is the second most frequent cause of cancer-related death worldwide. Combined surgery and chemo/radiotherapy give only a limited 5-year survival rate. Alternative therapeutic strategies such as immunotherapy are needed to improve this survival rate. Macrophages are functionally plastic cells. Type 1 macrophages (M1) inhibit, whereas type 2 macrophages (M2) promote, tumor growth. In this study, we examined the effects of in vitro repolarized tumor macrophages on gastric tumor growth in vivo. We demonstrated that peritoneal macrophages isolated from mouse forestomach carcinoma (MFC) tumor-bearing mice (TPM) displayed a M2 functional phenotype as indicated by a characteristic cytokine production profile and expression pattern of inducible nitric oxide synthase (iNOS) and arginase (Arg) of M2 macrophages. Treatment of TPM with type 1 cytokine IL-12 and IFN-gamma repolarized TPM toward the M1 phenotype as confirmed by a cytokine production profile and expression pattern of iNOS and Arg of typical M1 macrophages. Repolarized TPM significantly inhibits the growth of MFC tumors implanted subcutaneously compared to peritoneal macrophage (PM) isolated from normal animals, TPM, or M2 macrophages. Our study supports in vitro repolarization of macrophages as a potential immunotherapeutic strategy for gastric cancer. PMID:23879167

  4. Cadmium inhibits acid secretion in stimulated frog gastric mucosa

    SciTech Connect

    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

    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.

  5. Inhibition of isoleucyl-transfer ribonucleic acid synthetase in Echerichia coli by pseudomonic acid

    PubMed Central

    Hughes, Julia; Mellows, Graham

    1978-01-01

    The mode of action of the antibiotic pseudomonic acid has been studied in Escherichia coli. Pseudomonic acid strongly inhibits protein and RNA synthesis in vivo. The antibiotic had no effect on highly purified DNA-dependent RNA polymerase and showed only a weak inhibitory effect on a poly(U)-directed polyphenylalanine-forming ribosomal preparation. Chloramphenicol reversed inhibition of RNA synthesis in vivo. Pseudomonic acid had little effect on RNA synthesis in a regulatory mutant, E. coli B AS19 RCrel, whereas protein synthesis was strongly inhibited. In pseudomonic acid-treated cells, increased concentrations of ppGpp, pppGpp and ATP were observed, but the GTP pool size decreased, suggesting that inhibition of RNA synthesis is a consequence of the stringent control mechanism imposed by pseudomonic acid-induced deprivation of an amino acid. Of the 20 common amino acids, only isoleucine reversed the inhibitory effect in vivo. The antibiotic was found to be a powerful inhibitor of isoleucyl-tRNA synthetase both in vivo and in vitro. Of seven other tRNA synthetases assayed, only a weak inhibitory effect on phenylalanyl-tRNA synthetase was observed; this presumably accounted for the weak effect on polyphenylalanine formation in a ribosomal preparation. Pseudomonic acid also significantly de-repressed threonine deaminase and transaminase B activity, but not dihydroxyacid dehydratase (isoleucine-biosynthetic enzymes) by decreasing the supply of aminoacylated tRNAIle. Pseudomonic acid is the second naturally occurring inhibitor of bacterial isoleucyl-tRNA synthetase to be discovered, furanomycin being the first. PMID:365175

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

    PubMed Central

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

    2006-01-01

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

  7. Inhibition of reticulo-ruminal motility by volatile fatty acids and lactic acid in sheep.

    PubMed Central

    Gregory, P C

    1987-01-01

    1. A study was made of the influence on reticulo-ruminal motility, recorded by electromyography, of ruminal infusions of volatile fatty acids (VFAs) and lactic acid in twenty-four sheep maintained by intragastric infusion of a complete liquid diet, in three sheep fed grass pellets, and in nine chronically vagotomized sheep; abomasal and duodenal infusions of VFA and lactic acid were tested in five sheep fed grass pellets. 2. Ruminal infusions of VFAs and lactic acid progressively inhibited the amplitude of the reticulo-ruminal contractions. In many experiments there was no effect on contraction frequency until the cessation of all reticulo-ruminal contractions at which point the maximal concentration of VFA recorded in the abomasum was 28 mM, and that of lactic acid was 20 mM. 3. The concentrations of undissociated VFAs causing cessation of reticulo-ruminal contractions in the vagus-intact sheep were very similar to the concentrations causing abolition of the organized intrinsic motility of the chronically vagotomized sheep. 4. The inhibition of reticulo-ruminal motility with ruminal infusions of mixtures of VFAs and of lactic acid together with VFAs could largely be explained by the sum of the effects of the individual acids present. 5. Abomasal infusion of VFA or lactic acid inhibited the amplitude of ruminal, especially primary ruminal, contractions at concentrations of undissociated acid of 60 mM and above and increased the frequency of reticulum and primary ruminal contractions at about 80 mM. 6. Duodenal infusion of VFAs and lactic acid (100 mM, 5 ml/min) strongly inhibited abomasal motility without affecting reticulo-ruminal motility, and at a higher rate (100 mM, 10 ml/min) abolished motility and inhibited both the amplitude and frequency of reticulo-ruminal contractions. 7. It is concluded that the initial inhibition of reticulo-ruminal motility in ruminal acidosis is unlikely to involve any significant influence from duodenal, or abomasal receptors. The final cessation of reticulo-ruminal motility with ruminal acidosis could involve local effects of VFAs in the reticulo-rumen as well as through excitation of acid-sensitive reticulo-ruminal receptors. PMID:3625553

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

    Microsoft Academic Search

    F. Seidlová; J. Krekule; L. Teltscherová

    1967-01-01

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

  9. Griseofulvin inhibits the growth of adrenocortical cancer cells in vitro.

    PubMed

    Bramann, E L; Willenberg, H S; Hildebrandt, B; Müller-Mattheis, V; Schott, M; Scherbaum, W A; Haase, M

    2013-04-01

    Supernumerary centrosomes and aneuploidy are associated with a malignant phenotype of tumor cells. Centrosomal clustering is a mechanism used by cancer cells with supernumerary centrosomes to solve the threatening problem of multipolar spindles. Griseofulvin is an antifungal substance that interferes with the microtubule apparatus and inhibits centrosomal clustering. It has also been demonstrated that griseofulvin inhibits the growth of tumor cells in vitro and in vivo. However, it is not yet known whether treatment with griseofulvin inhibits growth of adrenocortical tumor cells. We studied the viability and antiproliferative effects of griseofulvin on cultured NCI-H295R adrenocortical carcinoma cells using Wst-1-, BrdUrd-, and [³H]-thymidine assays. For the detection of apoptosis we used a caspase 3/7 cleavage assay and light microscopy techniques. We observed that incubation with griseofulvin for 24-48 h leads to a decrease in the viability and proliferation of NCI-H295R cells in a dose-dependent manner. Significant effects could be observed after incubation with griseofulvin as measured by Wst-1-, BrdUrd-, and [³H]dT- uptake assays. Apoptosis of NCI-H295R cells was increased in a dose-dependent manner up to 4.5-fold after incubation with griseofulvin 40 ?M for 24 h as shown by caspase 3/7 cleavage assay and light microscopy. With regard to new treatment strategies for adrenocortical cancer, griseofulvin, and possibly other agents, which interfere with the microtubule apparatus and inhibit centrosomal clustering, may turn out to be interesting targets for further research. PMID:23111828

  10. Inhibition of Growth by Amber Suppressors in Yeast

    PubMed Central

    Liebman, Susan W.; Sherman, Fred

    1976-01-01

    Strains of the yeast Saccharomyces cerevisiae that contain highly efficient amber (UAG) suppressors grow poorly on nutrient medium, while normal or nearly normal growth rates are observed when these strains lose the suppressors or when the suppressors are mutated to lower efficiencies. The different growth rates account for the accumulation of mutants with lowered efficiencies in cultures of strains with highly efficient amber suppressors. Genetic analyses indicate that one of the mutations with a lowered efficiency of suppression is caused by an intragenic mutation of the amber suppressor. The inhibition of growth caused by excessive suppression is expected to be exacerbated when appropriate suppressors are combined together in haploid cells if two suppressors act with a greater efficiency than a single suppressor. Such retardation of growth is observed with combinations of two UAA (ochre) suppressors (Gilmore 1967) and with combinations of two UAG suppressors when the efficiencies of each of the suppressors are within a critical range. In contrast, combinations of a UAA suppressor and a UAG suppressor do not affect growth rate. Apparently while either excessive UAA or excessive UAG suppression is deleterious to yeast, a moderate level of simultaneous UAA and UAG suppression is not. PMID:177332

  11. Tranexamic acid concentrations associated with human seizures inhibit glycine receptors.

    PubMed

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

    2012-12-01

    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

  12. Modified lactic Acid bacteria detect and inhibit multiresistant enterococci.

    PubMed

    Borrero, Juan; Chen, Yuqing; Dunny, Gary M; Kaznessis, Yiannis N

    2015-03-20

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

  13. Aurin tricarboxylic acid inhibits adhesion of platelets to subendothelium.

    PubMed

    Owens, M R; Holme, S

    1996-01-15

    Aurin-tricarboxylic acid (ATA) is a polycarboxylated compound which binds to high molecular weight multimers of von Willebrand factor (vWf), effectively preventing binding of vWf to platelet membrane GPIb. By this mechanism, ATA inhibits shear-induced platelet aggregation as well as ristocetin-induced platelet aggregation/agglutination, both of which require interaction of platelets and vWf. Although it is reasonable to assume that ATA might also interfere with platelet adhesion, the effects of ATA on this aspect of platelet function have not been described. We report effects of ATA on adhesion of freshly prepared radiolabeled platelets to subendothelium of everted rabbit aorta utilizing a model which permits observations at varying shear rates. Using concentrations of ATA that inhibited aggregation induced by either ristocetin or the more potent agonist, thrombin, ATA was found to inhibit adhesion of platelets in a dose-dependent manner. In addition, ATA was found to inhibit platelet aggregation in response to the agonists ristocetin or thrombin. The inhibitory effect of ATA on thrombin-induced aggregation was completely erased by washing and resuspension in a thrombin-free medium, indicating that ATA does not have any lasting effects on the platelet response to thrombin. In plasma coagulation tests, using either the prothrombin time, activated partial thromboplastin time of thrombin time, ATA prolonged clotting times in a dose-dependent manner. PMID:8822132

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

    PubMed

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

    1984-08-01

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

  15. Identification of volatile compounds produced by the bacterium Burkholderia tropica that inhibit the growth of fungal pathogens

    PubMed Central

    Tenorio-Salgado, Silvia; Tinoco, Raunel; Vazquez-Duhalt, Rafael; Caballero-Mellado, Jesus; Perez-Rueda, Ernesto

    2013-01-01

    It has been documented that bacteria from the Burkholderia genera produce different kinds of compounds that inhibit plant pathogens, however in Burkholderia tropica, an endophytic diazotrophic and phosphate-solubilizing bacterium isolated from a wide diversity of plants, the capacity to produce antifungal compounds has not been evaluated. In order to expand our knowledge about Burkholderia tropica as a potential biological control agent, we analyzed 15 different strains of this bacterium to evaluate their capacities to inhibit the growth of four phytopathogenic fungi, Colletotrichum gloeosporioides, Fusarium culmorum, Fusarium oxysporum and Sclerotium rolffsi. Diverse analytical techniques, including plant root protection and dish plate growth assays and gas chromatography-mass spectroscopy showed that the fungal growth inhibition was intimately associated with the volatile compounds produced by B. tropica and, in particular, two bacterial strains (MTo293 and TTe203) exhibited the highest radial mycelial growth inhibition. Morphological changes associated with these compounds, such as disruption of fungal hyphae, were identified by using photomicrographic analysis. By using gas chromatography-mass spectroscopy technique, 18 volatile compounds involved in the growth inhibition mechanism were identified, including ?-pinene and limonene. In addition, we found a high proportion of bacterial strains that produced siderophores during growth with different carbon sources, such as alanine and glutamic acid; however, their roles in the antagonism mechanism remain unclear. PMID:23680857

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

    PubMed

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

    2013-01-01

    While Streptococcus pyogenes is consistently susceptible toward penicillin, therapeutic failure of penicillin treatment has been reported repeatedly and a considerable number of patients exhibit allergic reactions to this substance. At the same time, streptococcal resistance to alternative antibiotics, e.g., macrolides, has increased. Taken together, these facts demand the development of novel therapeutic strategies. In this study, S. pyogenes growth was inhibited by application of peptide-conjugated antisense-peptide nucleic acids (PNAs) specific for the essential gyrase A gene (gyrA). Thereby, HIV-1 Tat peptide-coupled PNAs were more efficient inhibitors of streptococcal growth as compared with (KFF)3K-coupled PNAs. Peptide-anti-gyrA PNAs decreased the abundance of gyrA transcripts in S. pyogenes. Growth inhibition by antisense interference was enhanced by combination of peptide-coupled PNAs with protein-level inhibitors. Antimicrobial synergy could be detected with levofloxacin and novobiocin, targeting the gyrase enzyme, and with spectinomycin, impeding ribosomal function. The prospective application of carrier peptide-coupled antisense PNAs in S. pyogenes covers the use as an antimicrobial agent and the employment as a knock-down strategy for the investigation of virulence factor function.Molecular Therapy-Nucleic Acids (2013) 2, e132; doi:10.1038/mtna.2013.62; published online 5 November 2013. PMID:24193033

  17. Cell proliferation inhibition and alterations in retinol esterification induced by phytanic acid and docosahexaenoic acid

    Microsoft Academic Search

    Xiao-Han Tang; Moo-Jin Suh; Rong Li; Lorraine J. Gudas

    2006-01-01

    We investigated the effects of two natural dietary retinoid X receptor (RXR) ligands, phytanic acid (PA) and docosahexaenoic acid (DHA), on proliferation and on the metabolism of retinol (vitamin A) in both cultured normal human prostate epithelial cells (PrECs) and PC-3 prostate carcinoma cells. PA and DHA inhibited the proliferation of the parental PC-3 cells and PC-3 cells engineered to

  18. Hypothiocyanous acid oxidation of tubulin cysteines inhibits microtubule polymerization

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

    Yang, Xiaochun; Duan, Xuanchu

    2013-01-01

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

  20. [Growth inhibition of Microcystis aeruginosa in packed-bed discharge plasma Reactor].

    PubMed

    Wang, Cui-hua; Li, Guo-feng; Wu, Yan; Wang, Yu

    2008-02-01

    The paper discussed the effect of the gas flow rate and the addition of glass pellets dielectric on the growth inhibition of Microcystis aeruginosa (M. aeruginosa) and the concentration of hydrogen peroxide, the effect of energy input and pH on the growth inhibition of M. aeruginosa and the effect of packed-bed reactor on the algal Chl-a and cell density. The results show that the increasing of the gas flow rate and the addition of glass pellets dielectric enhance the effect of the discharge plasma reactor on the growth inhibition of M. aeruginosa immediately after discharge, but the effect is unobvious. The algal optical density slightly increases and then markedly decreases during the incubation period, e.g., the removal efficiency of the algal optical density is high to 87.3% at the end of the fifth day at an air flow rate of 0.75 m3/h after 40 min treatment in the packed-bed discharge plasma reactor. The concentration of hydrogen peroxide is enhanced by the increase in the gas flow rate and the addition of glass pellets dielectric into the discharge plasma reactor, too, especially the concentration of hydrogen peroxide enhanced from 4.6 micromol/L to 38.3 micromol/L by the addition of glass pellets dielectric, which will enhance the destructive effect of hydrogen peroxide on the algae during the incubation period. The effect of the growth inhibition of M. aeruginosa is obvious with the increasing in the energy input into the packed-bed discharge plasma reactor. The effect of the alkaline solution on the growth inhibition of M. aeruginosa is more higher than that of the acidic solution, and the value of pH is increased under the acidic condition and decreased under the alkaline condition, but the tread of pH is to be neutral during the incubation period. The decrease of the content of Chl-a and cell density is marked in this reactor, and at the end of the fifth day, the removal efficiencies of Chl-a and cell density are high to 100%. PMID:18613507

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  2. Use of virginiamycin to control the growth of lactic acid bacteria during alcohol fermentation

    Microsoft Academic Search

    S H Hynes; D M Kjarsgaard; K C Thomas; W M Ingledew

    1997-01-01

      The antibiotic virginiamycin was investigated for its effects on growth and lactic acid production by seven strains of lactobacilli\\u000a during the alcoholic fermentation of wheat mash by yeast. The lowest concentration of virginiamycin tested (0.5?mg Lactrol\\u000a TMkg?1 mash), was effective against most of the lactic acid bacteria under study, but Lactobacillus plantarum was not significantly inhibited at this concentration. The

  3. RPA Inhibition increases Replication Stress and Suppresses Tumor Growth

    PubMed Central

    Glanzer, Jason G.; Liu, Shengqin; Wang, Ling; Mosel, Adam; Peng, Aimin; Oakley, Greg G.

    2014-01-01

    The ATR/Chk1 pathway is a critical surveillance network that maintains genomic integrity during DNA replication by stabilizing the replication forks during normal replication to avoid replication stress. One of the many differences between normal cells and cancer cells is the amount of replication stress that occurs during replication. Cancer cells with activated oncogenes generate increased levels of replication stress. This creates an increased dependency on the ATR/Chk1 pathway in cancer cells and opens up an opportunity to preferentially kill cancer cells by inhibiting this pathway. In support of this idea, we have identified a small molecule termed HAMNO ((1Z)-1-[(2-hydroxyanilino)methylidene]naphthalen-2-one), a novel protein interaction inhibitor of replication protein A (RPA), a protein involved in the ATR/Chk1 pathway. HAMNO selectively binds the N-terminal domain of RPA70, effectively inhibiting critical RPA protein interactions which rely on this domain. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. By itself, HAMNO treatment creates DNA replication stress in cancer cells that are already experiencing replication stress, but not in normal cells, and it acts synergistically with etoposide to kill cancer cells in vitro and slow tumor growth in vivo. Thus, HAMNO illustrates how RPA inhibitors represent candidate therapeutics for cancer treatment, providing disease selectivity in cancer cells by targeting their differential response to replication stress. PMID:25070753

  4. Lactoferrin inhibits the growth of nasal polyp fibroblasts.

    PubMed

    Nadolska, Beata; Fr?czek, Marcin; Kr?cicki, Tomasz; Koci?ba, Maja; Zimecki, Micha?

    2010-01-01

    The aim of this study was to evaluate the effects of lactoferrin (LF) on the growth of fibroblasts derived from nasal polyps. We showed that the proliferation of fibroblasts was inhibited in a dose-dependent manner by both native and recombinant LF. The greatest inhibition of proliferation was caused by human milk-derived, iron-saturated LF. The inhibition of fibroblast proliferation was not species specific because bovine LF also was active. The interaction between LFs and a putative cell receptor did not depend on the sugar composition of the glycan moiety of the LF molecule because lactoferrins of different origins were active and the addition of monosaccharides to the cultures did not block proliferation. However, the treatment of fibroblasts with sodium chlorate (an inhibitor of glycosaminoglycan sulfation) or the addition of heparin abolished the inhibitory effect of LF, suggesting that LF binds heparan sulfate-containing proteoglycans. The significance of LF in nasal excretions in controlling polyp formation is discussed. PMID:21273671

  5. Cancer growth and its inhibition in terms of coherence.

    PubMed

    Popp, Fritz-Albert

    2009-01-01

    It is shown that a molecular origin for growth inhibition is rather unlikely because the cross-sectional area of inhibitory forces in a cell population cannot exceed more than about 10(-8) Dalton. A model of the time dependence of cell number N(t), where t is the time, is based on biophotons and explains without any contradiction to known experimental results growth regulation in terms of the factor a = 1/T, which stimulates the cell division rate dN/dt and the factor b = dT/dN(1/T(2)), which inhibits cell division. It accounts for the total cell division rate dN/dt = aN(t) - bN(2)(t). For adults, T is the coherence time of about 10(6) s, corresponding to the longest lifetime of cell organelles in men, while dT/dN = 10(-7) s corresponds to the resolution time of the cell population which is always the average time interval between two cell loss events. Our model follows a stringently holistic approach to describing a cell population as an entity, regulated by a fully coherent (biophoton) field. PMID:19337895

  6. Praziquantel Synergistically Enhances Paclitaxel Efficacy to Inhibit Cancer Cell Growth

    PubMed Central

    Wu, Zhen Hua; Lu, Ming-ke; Hu, Long Yu; Li, Xiaotong

    2012-01-01

    The major challenges we are facing in cancer therapy with paclitaxel (PTX) are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel (PZQ), an anti-parasite agent, could greatly enhance the anticancer efficacy of PTX in various cancer cell lines, including PTX-resistant cell lines. Based on the combination index value, we demonstrated that PZQ synergistically enhanced PTX-induced cell growth inhibition. The co-treatment of PZQ and PTX also induced significant mitotic arrest and activated the apoptotic cascade. Moreover, PZQ combined with PTX resulted in a more pronounced inhibition of tumor growth compared with either drug alone in a mouse xenograft model. We tried to investigate the possible mechanisms of this synergistic efficacy induced by PZQ and PTX, and we found that the co-treatment of the two drugs could markedly decrease expression of X-linked inhibitor of apoptosis protein (XIAP), an anti-apoptotic protein. Our data further demonstrated that down-regulation of XIAP was required for the synergistic interaction between PZQ and PTX. Together, this study suggested that the combination of PZQ and PTX may represent a novel and effective anticancer strategy for optimizing PTX therapy. PMID:23251610

  7. Inhibition of bacterial peptide deformylase by biaryl acid analogs.

    PubMed

    Green, B G; Toney, J H; Kozarich, J W; Grant, S K

    2000-03-15

    Peptide deformylase is an essential eubacterial metalloenzyme involved in the maturation of proteins by cleaving the N-formyl group from N-blocked methionine polypeptides. Biaryl acid analogs containing tetrazole, acyl sulfonamide, or carboxylate pharmacophores were found to be potent inhibitors of recombinant Escherichia coli peptide deformylase. Two of these compounds, a biphenyl tetrazole, compound 1, and a biphenyl acyl sulfonamide, compound 4, were competitive inhibitors with K(i) values of 1.2 and 6.0 microM, respectively. By analogy to the binding of related compounds to other metalloenzymes such as Bacteroides fragilis metallo-beta-lactamase CcrA and human carbonic anhydrase, a mechanism of inhibition is proposed for these peptide deformylase inhibitors where the acidic moieties form direct ionic interactions with the active site metal cation. PMID:10700392

  8. Hyperbaric hyperoxia reversibly inhibits erythrocyte phospholipid fatty acid turnover

    NASA Technical Reports Server (NTRS)

    Dise, Craig A.; Clark, James M.; Lambersten, Christian J.; Goodman, David B. P.

    1987-01-01

    The effect of hyperbaric hyperoxia on the acylation of membrane phospholipid was studied by measuring the rates of activation of exogenous tritiated oleic acid to acyl thioester and of transesterification of the thioester into membrane phospholipids in intact human erythrocytes obtained 1 h after an exposure of the subjects to a hyperbaric oxygen atmosphere (3.5 h, 100 pct O2, 3 ATA). Exposure to pure oxygen was found to inhibit both the acylation and transesterification reactions by more than 30 percent, with partial recovery detected 24 h later. On the other hand, no rate changes were observed when isolated membranes from the same batches of cells were used in similar experiments. It is suggested that the decrease in the incorporation of tritiated oleic acid after hyperbaric hyperoxia may reflect an early event in the pathogenesis of oxygen-induced cellular injury and that it may be a useful index for the assessment of the tolerance of tissues to hyperoxia.

  9. Inhibition of Ileal Water Absorption by Intraluminal Fatty Acids INFLUENCE OF CHAIN LENGTH, HYDROXYLATION, AND CONJUGATION OF FATTY ACIDS

    PubMed Central

    Ammon, Helmut V.; Phillips, Sidney F.

    1974-01-01

    The influence of fatty acids on ileal absorption of water, electrolytes, glucose, and taurocholate was examined in Thirty-Vella fistulas in five mongrel dogs. Fatty acid absorption also was measured. Segments of terminal ileum were perfused at steady state with isotonic electrolyte solutions containing 11.2 mM glucose, 4.5 mM taurocholate, and 0.1-5.0 mM fatty acid. Three C18 fatty acids, oleic acid, 10(9)-hydroxystearic acid, and ricinoleic acid, completely inhibited water absorption at 5 mM. Sodium, chloride, and potassium absorptions were inhibited in parallel with absorption of water. Differences between the potencies of C18 fatty acids were apparent when lesser concentrations were perfused. Dodecanoic and decanoic acids were as effective as C18 fatty acids at 5 mM but octanoic and hexanoic acids were ineffective. The polar group of C18 fatty acids was modified by conjugating oleic and ricinoleic acids with taurine. When these compounds and a substituted C18 fatty acid, p-n-decylbenzenesulfonate, were perfused, water absorption was also inhibited. Short-chain fatty acids (C3 and C4) and their hydroxylated derivatives were ineffective at 5 mM. When water absorption was inhibited, absorption of glucose and taurocholate was decreased. We speculate that the phenomenon of inhibition of water and electrolyte absorption by fatty acids may be relevant to steatorrhea and diarrhea in man. Images PMID:4808636

  10. Mirtazapine Inhibits Tumor Growth via Immune Response and Serotonergic System

    PubMed Central

    Fang, Chun-Kai; Chen, Hong-Wen; Chiang, I-Tsang; Chen, Chia-Chieh; Liao, Jyh-Fei; Su, Ton-Ping; Tung, Chieh-Yin; Uchitomi, Yosuke; Hwang, Jeng-Jong

    2012-01-01

    To study the tumor inhibition effect of mirtazapine, a drug for patients with depression, CT26/luc colon carcinoma-bearing animal model was used. BALB/c mice were randomly divided into six groups: two groups without tumors, i.e. wild-type (no drug) and drug (mirtazapine), and four groups with tumors, i.e. never (no drug), always (pre-drug, i.e. drug treatment before tumor inoculation and throughout the experiment), concurrent (simultaneously tumor inoculation and drug treatment throughout the experiment), and after (post-drug, i.e. drug treatment after tumor inoculation and throughout the experiment). The “psychiatric” conditions of mice were observed from the immobility time with tail suspension and spontaneous motor activity post tumor inoculation. Significant increase of serum interlukin-12 (sIL-12) and the inhibition of tumor growth were found in mirtazapine-treated mice (always, concurrent, and after) as compared with that of never. In addition, interferon-? level and immunocompetent infiltrating CD4+/CD8+ T cells in the tumors of mirtazapine-treated, tumor-bearing mice were significantly higher as compared with that of never. Tumor necrosis factor-? (TNF-?) expressions, on the contrary, are decreased in the mirtazapine-treated, tumor-bearing mice as compared with that of never. Ex vivo autoradiography with [123I]ADAM, a radiopharmaceutical for serotonin transporter, also confirms the similar results. Notably, better survival rates and intervals were also found in mirtazapine-treated mice. These findings, however, were not observed in the immunodeficient mice. Our results suggest that tumor growth inhibition by mirtazapine in CT26/luc colon carcinoma-bearing mice may be due to the alteration of the tumor microenvironment, which involves the activation of the immune response and the recovery of serotonin level. PMID:22808019

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

    PubMed Central

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

    2013-01-01

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

  12. Specificity of growth inhibition of melanoma by 4-hydroxyanisole

    SciTech Connect

    Kulkarni, G.A.; Nathanson, L.

    1989-01-01

    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.

  13. Parafibromin inhibits cancer cell growth and causes G1 phase arrest

    SciTech Connect

    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

    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.

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

    PubMed

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

    2010-11-01

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

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

    PubMed Central

    2012-01-01

    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

  16. Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons

    PubMed Central

    Beckmann, Nadine; Sharma, Deepa; Gulbins, Erich; Becker, Katrin Anne; Edelmann, Bärbel

    2014-01-01

    Amitriptyline, a tricyclic antidepressant, has been used in the clinic to treat a number of disorders, in particular major depression and neuropathic pain. In the 1970s the ability of tricyclic antidepressants to inhibit acid sphingomyelinase (ASM) was discovered. The enzyme ASM catalyzes the hydrolysis of sphingomyelin to ceramide. ASM and ceramide were shown to play a crucial role in a wide range of diseases, including cancer, cystic fibrosis, diabetes, Alzheimer's disease, and major depression, as well as viral (e.g., measles virus) and bacterial (e.g., Staphylococcus aureus, Pseudomonas aeruginosa) infections. Ceramide molecules may act in these diseases by the alteration of membrane biophysics, the self-association of ceramide molecules within the cell membrane and the ultimate formation of larger ceramide-enriched membrane domains/platforms. These domains were shown to serve the clustering of certain receptors such as CD95 and may also act in the above named diseases. The potential to block the generation of ceramide by inhibiting the ASM has opened up new therapeutic approaches for the treatment of these conditions. Since amitriptyline is one of the longest used clinical drugs and side effects are well studied, it could potentially become a cheap and easily accessible medication for patients suffering from these diseases. In this review, we aim to provide an overview of current in vitro and in vivo studies and clinical trials utilizing amitriptyline to inhibit ASM and contemplate possible future applications of the drug. PMID:25228885

  17. Proteolytic Pathways Induced by Herbicides That Inhibit Amino Acid Biosynthesis

    PubMed Central

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

    2013-01-01

    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

  18. Effect of saccharin on growth and acid production of glucose-grown pathogenic and oral bacteria.

    PubMed

    Linke, H A; Doyle, G A

    1985-01-01

    Growth and acid production of glucose-grown Gram-positive and Gram-negative rods as well as cocci from the human oral cavity were studied in the presence of 0.02 to 20.00 mg/ml sodium saccharin. All Gram-positive rods, i.e. Actinomyces viscosus, Lactobacillus acidophilus, Bacillus subtilis and Corynebacterium diphtheriae, and Gram-positive cocci, i.e. Streptococcus spp, Staphylococcus aureus and Micrococcus luteus, were significantly inhibited by saccharin, especially at the higher concentrations. While Gram-negative cocci, i.e. Veillonella sp and Neisseria sicca were strongly inhibited by all tested saccharin concentrations, Gram-negative rods, i.e. the enterics and Acinetobacter sp, exhibited little if any inhibition. Saccharin caused a significant reduction in fermentative acid production congruent with observed growth. PMID:4033457

  19. Inadequate inhibition of host RNA polymerase restricts T7 bacteriophage growth on hosts

    E-print Network

    Richardson, Charles C.

    Inadequate inhibition of host RNA polymerase restricts T7 bacteriophage growth on hosts with T7 bacteriophage growth. We show here that inhibition of T7 phage growth by udk overexpression can-studied bacteriophage T7 have no known function. In addition, the function of many genetic elements, such as the re

  20. Synthesis and cholinesterase inhibition of cativic acid derivatives.

    PubMed

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

    2014-08-01

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

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

    Microsoft Academic Search

    Marco Kai; Uta Effmert; Gabriele Berg; Birgit Piechulla

    2007-01-01

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

  2. A FACTOR FROM NORMAL TISSUES INHIBITING TUMOR GROWTH

    PubMed Central

    Murphy, James B.; Sturm, Ernest

    1934-01-01

    Extracts of desiccated embryo skin and placenta have been found to exert a definite retarding action on the growth of two transplantable carcinomas of mice, but they were without effect on sarcomas. In tests involving some 828 inoculations of the tumor cells and the extracts, complete suppression of growth occurred in from 55 to 71 per cent of instances, as compared with 21 to 27 per cent in the controls, and where growth was not completely suppressed some retardation was found in practically every instance. To judge from findings in rabbits the inhibitor is not demonstrable in the placenta until the beginning of the second third of pregnancy, reaches its maximum by the last third, but disappears about 2 or 3 days before term. Extracts of fresh placenta are without effect, and no very definite inhibition was noted in extracts of a variety of other desiccated or fresh tissues. The conclusions here reported are based on the results of over 3800 inoculations. PMID:19870301

  3. Rat parietal cell function after prolonged inhibition of gastric acid secretion.

    PubMed

    Larsson, H; Carlsson, E; Ryberg, B; Fryklund, J; Wallmark, B

    1988-01-01

    Female rats were treated orally for 3 mo with omeprazole (40 and 400 mumol/kg). Both doses caused total inhibition of gastric acid secretion and recovery was parallel to that of H+-K+-ATPase activity (30-50 and 60-80% inhibition 24 h after doses, respectively). The H+-K+-ATPase activity returned to control levels within 1 wk after the last dose. Plasma gastrin levels were dose-dependently increased during treatment but reversed to control levels within 9 days after the last dose. Parallel with a general increase in corpus mucosal mass, both pepsinogen and H+-K+-ATPase total content increased. However, their tissue concentrations did not differ from control values, suggesting that neither parietal nor chief cell density are changed by omeprazole treatment and also that their growth is parallel to the general hyperplasia. In contrast, the oxyntic mucosal histamine concentration was increased, indicating an increase in the enterochromaffin-like (ECL) cell density. Maximal capacity of the mucosa to secrete acid increased in parallel with the increase in mucosal mass and total H+-K+-ATPase content. However, basal acid secretion did not differ between treatment groups. Increased capacity slowly declined toward control levels over the 70-day recovery period after withdrawal of omeprazole. These results suggest that hypergastrinemia, induced in the rat by pharmacological inhibition of gastric acid secretion, causes a hyperplasia of oxyntic mucosal cells, ECL cells growing faster than the others. The hyperplastic mucosa has an increased capacity to produce acid and is functionally normal. PMID:2827515

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

    Microsoft Academic Search

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

    2002-01-01

    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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2013-01-01

    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

  7. Analysis of an ampicillin propyl ester prodrug which inhibits the growth of Escherichia coli.

    PubMed

    Bartzatt, Ronald; Malesa, Cynthia

    2002-10-01

    An ampicillin prodrug was synthesized by utilizing the chemical reaction of ampicillin with diazopropane (CH(3)CH(2)CHN(2)) in an organic solvent. The result is esterification of the carboxylic acid functional group. The ampicillin prodrug is a solid that forms yellow crystals which are soluble in water and LB agarose media. The ampicillin prodrug was stable for more than 10 weeks when stored at < or = 0.0 degrees C. The prodrug has reduced hydrogen-bonding capability compared with the unmodified structure of ampicillin. Evaluation of the logP parameter (the octanol/water partition coefficient) indicates that the ampicillin prodrug (logP=1.773) has increased lipophilic characteristics relative to the unmodified ampicillin structure (logP=1.06). The lipophilic substituent constant for the esterification of the carboxylic acid is 0.713, a positive value which indicates that the substituent has a lipophilic nature. The ampicillin prodrug was solubilized into LB agarose media at a concentration of 0.228 mg/ml, and was found to induce 100% growth inhibition of an ampicillin-susceptible and streptomycin-resistant Escherichia coli strain (designated DH1), and induced greater than 30% growth inhibition of an ampicillin-resistant E. coli strain (designated PKK). Synthesis of this prodrug utilizing a diazoalkane was highly efficient, with no undesirable by-products being formed. PMID:12241549

  8. The kinetics of process dependent ammonia inhibition of methanogenesis from acetic acid.

    PubMed

    Wilson, Christopher Allen; Novak, John; Takacs, Imre; Wett, Bernhard; Murthy, Sudhir

    2012-12-01

    Advanced anaerobic digestion processes aimed at improving the methanization of sewage sludge may be potentially impaired by the production of inhibitory compounds (e.g. free ammonia). The result of methanogenic inhibition is relatively high effluent concentrations of acetic acid and other soluble organics, as well as reduced methane yields. An extreme example of such an advanced process is the thermal hydrolytic pretreatment of sludge prior to high solids digestion (THD). Compared to a conventional mesophilic anaerobic digestion process (MAD), THD operates in a state of constant inhibition driven by high free ammonia concentrations, and elevated pH values. As such, previous investigations of the kinetics of methanogenesis from acetic acid under uninhibited conditions do not necessarily apply well to the modeling of extreme processes such as THD. By conducting batch ammonia toxicity assays using biomass from THD and MAD reactors, we compared the response of these communities over a broad range of ammonia inhibition. For both processes, increased inhibitor concentrations resulted in a reduction of biomass growth rate (r(max) = ?(max)?X) and a resulting decrease in the substrate half saturation coefficient (K(S)). These two parameters exhibited a high degree of correlation, suggesting that for a constant transport limited system, the K(S) was mostly a linear function of the growth rate. After correcting for reactor pH and temperature, we found that the THD and MAD biomass were both able to perform methanogenesis from acetate at high free ammonia concentrations (equivalent to 3-5 g/L total ammonia nitrogen), albeit at less than 30% of their respective maximum rates. The reduction in methane production was slightly less pronounced for the THD biomass than for MAD, suggesting that the long term exposure to ammonia had selected for a methanogenic pathway less dependent on those organisms most sensitive to ammonia inhibition (i.e. aceticlastic methanogens). PMID:23062786

  9. Distinct Muscarinic Receptors Inhibit Release of gamma-Aminobutyric Acid and Excitatory Amino Acids in Mammalian Brain

    Microsoft Academic Search

    S. Sugita; N. Uchimura; Z.-G. Jiang; R. A. North

    1991-01-01

    Intracellular recordings were made from neurons of rat lateral amygdala, nucleus accumbens, and striatum in vitro. Synaptic potentials mediated by gamma-aminobutyric acid and by excitatory amino acids were isolated pharmacologically by using receptor antagonists, and their amplitudes were used as a measure of transmitter release. Muscarine and acetylcholine inhibited the release of both gamma-aminobutyric acid and excitatory amino acids, but

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

    PubMed Central

    Ren, MingQiang; Ghidoni, Riccardo; Sacchi, Nicoletta

    2007-01-01

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

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

    Microsoft Academic Search

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

    1993-01-01

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

  12. Inhibition of bone resorption and growth of breast cancer in the bone microenvironment.

    PubMed

    Buijs, Jeroen T; Que, Ivo; Löwik, Clemens W G M; Papapoulos, Socrates E; van der Pluijm, Gabri

    2009-02-01

    Breast cancer frequently metastasizes to bone, where tumor cells induce osteoclasts to locally destroy bone. During bone resorption, growth factors are locally released that may support bone metastatic growth. Differently from most other tissues, drugs that can limit local turnover, such as bisphosphonates and osteoprotegerin (OPG), are available for bone. We examined the hypothesis that inhibition of bone resorption by two different mechanisms may also affect the growth of cancer cells in bone. For this, we tested the effects of high doses of OPG and zoledronic acid (ZOL) on progression of MDA-231-B/Luc+ breast cancer cells in the bone microenvironment using whole body bioluminescent reporter imaging (BLI). Both treatments significantly inhibited the development of radiographically detectable osteolytic lesions. Histologic examination corroborated the radiographic findings, showing that both treatments preserved the integrity of bone trabeculae and prevented bone destruction (significantly higher trabecular bone volumes vs. vehicle). However, whereas practically no TRAcP-positive osteoclasts were observed in tibiae preparations of animals treated with Fc-OPG, TRAcP-positive osteoclasts were still present in the animals treated with ZOL. Intra-bone tumor burden was reduced with ZOL and Fc-OPG treatment. Although there appeared to be a trend for less overall total tumor burden upon treatment with both compounds, this was not significant as assessed by BLI and histomorphometric analysis due to the extramedullary growth of cancer cells which was not affected by these treatments. Collectively, anti-resorptive agents with different mechanisms of action - ZOL and OPG - significantly reduced cancer-induced osteolysis and intra-osseous tumor burden, but failed to restrain local tumor growth. However, interference with the bone micro-environmental growth support could still be of therapeutic relevance when given to patients early in the course of bone metastatic disease. PMID:19041433

  13. Inhibition of the reductive activation of a valyl-tRNA synthetase from yeast by unsaturated fatty acids and associated observations on newly found lipophilic substances from yeast.

    PubMed

    Black, S

    1985-01-10

    The reductive activation of a valyl-tRNA synthetase from yeast is strongly inhibited by 1-30 microM unsaturated fatty acids, and the inhibition is antagonized by 10-100 microM saturated fatty acids. Diethylstilbestrol also inhibits the activation. The possibility that unesterified palmitoleic and oleic acids are bona fide regulatory effectors is supported by a dramatic inverse relation between their cellular content and the growth rate of commercial bakers' yeast. An increase in the ratio of unsaturated to saturated acids with slowing growth in a laboratory strain, S288C, also supports the regulatory hypothesis. The free fatty acids are extracted into slightly acidified 50% alcohol together with traces of numerous novel lipophilic substances. One of these is suggested to function as a cofactor in conjunction with a heat-stable polypeptide that activates valyl-tRNA synthetase. PMID:3880744

  14. Exposure to Asulox Inhibits the Growth of Mosses

    PubMed Central

    ROWNTREE, J. K.; LAWTON, K. F.; RUMSEY, F. J.; SHEFFIELD, E.

    2003-01-01

    Asulox is a herbicide used to control bracken. Its effects on mosses were investigated to ascertain whether exposure proved as detrimental as found in parallel studies on pteridophytes. Mature gametophytes of 18 mosses were exposed to a range of concentrations of Asulox under standard conditions and the effects on growth monitored. Plants were cut to a standard length, exposed to Asulox solution for 24 h, grown for 3 weeks and total elongation (main stem and branches) measured. EC50 values were calculated and species ranked according to sensitivity. The effects of exposure on total elongation were compared with those on main stem elongation alone. Under the conditions tested, the total elongation of all species was inhibited after exposure to Asulox. The amount of elongation observed after exposure was different for different species and inhibition of elongation occurred at different exposure concentrations. A single regression equation was not adequate to describe the dose response curves of all species tested. An ability to produce secondary branches may confer increased tolerance to Asulox exposure. It is concluded that mosses suffer detrimental effects after exposure to Asulox at concentrations similar to those that affect fern gametophytes such as bracken. PMID:12933364

  15. Magnetic fluid hyperthermia inhibits the growth of breast carcinoma and downregulates vascular endothelial growth factor expression.

    PubMed

    Wang, Guihua; Xu, Derong; Chai, Qin; Tan, Xiaolang; Zhang, Yu; Gu, Ning; Tang, Jintian

    2014-05-01

    The application of magnetic fluid hyperthermia (MFH) with nanoparticles has been shown to inhibit tumor growth in several animal models. However, the feasibility of using MFH in vivo to treat breast cancer is uncertain, and the mechanism is unclear. In the present study, it was observed that the intratumoral administration of MFH induced hyperthermia significantly in rats with Walker-265 breast carcinomas. The hyperthermia treatment with magnetic nanoparticles inhibited tumor growth in vivo and promoted the survival of the tumor-bearing rats. Furthermore, it was found that MFH treatment downregulated the protein expression of vascular endothelial growth factor (VEGF) in the tumor tissue, as observed by immunohistochemistry. MFH treatment also decreased the gene expression of VEGF and its receptors, VEGF receptor 1 and 2, and inhibited angiogenesis in the tumor tissues. Taken together, these results indicate that the application of MFH with nanoparticles is feasible for the treatment of breast carcinoma. The MFH-induced downregulation of angiogenesis may also contribute to the induction of an anti-tumor effect. PMID:24765139

  16. Magnetic fluid hyperthermia inhibits the growth of breast carcinoma and downregulates vascular endothelial growth factor expression

    PubMed Central

    WANG, GUIHUA; XU, DERONG; CHAI, QIN; TAN, XIAOLANG; ZHANG, YU; GU, NING; TANG, JINTIAN

    2014-01-01

    The application of magnetic fluid hyperthermia (MFH) with nanoparticles has been shown to inhibit tumor growth in several animal models. However, the feasibility of using MFH in vivo to treat breast cancer is uncertain, and the mechanism is unclear. In the present study, it was observed that the intratumoral administration of MFH induced hyperthermia significantly in rats with Walker-265 breast carcinomas. The hyperthermia treatment with magnetic nanoparticles inhibited tumor growth in vivo and promoted the survival of the tumor-bearing rats. Furthermore, it was found that MFH treatment downregulated the protein expression of vascular endothelial growth factor (VEGF) in the tumor tissue, as observed by immunohistochemistry. MFH treatment also decreased the gene expression of VEGF and its receptors, VEGF receptor 1 and 2, and inhibited angiogenesis in the tumor tissues. Taken together, these results indicate that the application of MFH with nanoparticles is feasible for the treatment of breast carcinoma. The MFH-induced downregulation of angiogenesis may also contribute to the induction of an anti-tumor effect. PMID:24765139

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Resveratrol suppresses the proliferation of breast cancer cells by inhibiting fatty acid synthase signaling pathway.

    PubMed

    Khan, Arif; Aljarbou, Ahmad N; Aldebasi, Yousef H; Faisal, Syed M; Khan, Masood A

    2014-12-01

    In breast cancer cells, overexpression of human epidermal growth factor receptor 2 (HER2) increases the translation of fatty acid synthase (FASN) by altering the activity of PI3K/Akt signaling pathways. Cancer chemotherapy causes major side effects and is not effective enough in slowing down the progression of the disease. Earlier studies showed a role for resveratrol in the inhibition of FASN, but the molecular mechanisms of resveratrol-induced inhibition are not known. In the present study, we examined the novel mechanism of resveratrol on Her2-overexpressed breast cancer cells. The effect of resveratrol on the growth of breast cancer cells was assessed as percent cell viability by cytotoxicity-based MTT assay and the induction of apoptosis was determined by cell-death detection ELISA and flow cytometric analysis of Annexin-V-PI binding. Western immunobloting was used to detect signaling events in human breast cancer (SKBR-3) cells. Data showed that resveratrol-mediated down-regulation of FASN and HER2 genes synergistically induced apoptotic death in SKBR-3 cells. This concurrently caused a prominent up-regulation of PEA3, leads to down-regulation of HER2 genes. Resveratrol also alleviated the PI3K/Akt/mTOR signaling by down-regulation of Akt phosphorylation and up-regulation of PTEN expression. These findings suggest that resveratrol alters the cell cycle progression and induce cell death via FASN inhibition in HER2 positive breast cancer. PMID:25448084

  19. Rice varietal differences in bioactive bran components for inhibition of colorectal cancer cell growth.

    PubMed

    Forster, Genevieve M; Raina, Komal; Kumar, Ajay; Kumar, Sushil; Agarwal, Rajesh; Chen, Ming-Hsuan; Bauer, John E; McClung, Anna M; Ryan, Elizabeth P

    2013-11-15

    Rice bran chemical profiles differ across rice varieties and have not yet been analysed for differential chemopreventive bioactivity. A diverse panel of seven rice bran varieties was analysed for growth inhibition of human colorectal cancer (CRC) cells. Inhibition varied from 0% to 99%, depending on the variety of bran used. Across varieties, total lipid content ranged 5-16%, individual fatty acids had 1.4- to 1.9-fold differences, vitamin E isoforms (?-, ?-, ?-tocotrienols, and tocopherols) showed 1.3- to 15.2-fold differences, and differences in ?-oryzanol and total phenolics ranged between 100-275ng/mg and 57-146ngGAE/mg, respectively. Spearman correlation analysis was used to identify bioactive compounds implicated in CRC cell growth inhibitory activity. Total phenolics and ?-tocotrienol were positively correlated with reduced CRC cell growth (p<0.05). Stoichiometric variation in rice bran components and differential effects on CRC viability merit further evaluation elucidate their role in dietary CRC chemoprevention. PMID:23790950

  20. Rice Varietal Differences in Bioactive Bran Components for Inhibition of Colorectal Cancer Cell Growth

    PubMed Central

    Forster, Genevieve M.; Raina, Komal; Kumar, Ajay; Kumar, Sushil; Agarwal, Rajesh; Chen, Ming-Hsuan; Bauer, John E.; McClung, Anna M.; Ryan, Elizabeth P.

    2013-01-01

    Rice bran chemical profiles differ across rice varieties and have not yet been analyzed for differential chemopreventive bioactivity. A diverse panel of 7 rice bran varieties was analyzed for growth inhibition of human colorectal cancer (CRC) cells. Inhibition varied from 0–99%, depending on the variety of bran used. Across varieties, total lipid content ranged 5–16%, individual fatty acids had 1.4 to 1.9 fold differences, vitamin E isoforms (?-, ?-, ?- tocotrienols and tocopherols) showed 1.3 to 15.2 fold differences, and differences in ?- oryzanol and total phenolics ranged between 100–275 ng/mg and 57–146 ng GAE/mg, respectively. Spearman correlation analysis was used to identify bioactive compounds implicated in CRC cell growth inhibitory activity. Total phenolics and ?- tocotrienol were positively correlated with reduced CRC cell growth (p < 0.05). Stoichiometric variation in rice bran components and differential effects on CRC viability merit further evaluation elucidate their role in dietary CRC chemoprevention. PMID:23790950

  1. Effects of dissolved CO2 levels on the growth of Mannheimia succiniciproducens and succinic acid production.

    PubMed

    Song, Hyohak; Lee, Jeong Wook; Choi, Sol; You, Jong Kyun; Hong, Won Hi; Lee, Sang Yup

    2007-12-15

    A capnophilic rumen bacterium Mannheimia succiniciproducens produces succinic acid as a major fermentation end product under CO(2)-rich anaerobic condition. Since succinic acid is produced by carboxylation of C3 compounds during the fermentation, intracellular CO(2) availability is important for efficient succinic acid formation. Here, we investigated the metabolic responses of M. succiniciproducens to the different dissolved CO(2) concentrations (0-260 mM). Cell growth was severely suppressed when the dissolved CO(2) concentration was below 8.74 mM. On the other hand, cell growth and succinic acid production increased proportionally as the dissolved CO(2) concentration increased from 8.74 to 141 mM. The yields of biomass and succinic acid on glucose obtained at the dissolved CO(2) concentration of 141 mM were 1.49 and 1.52 times higher, respectively, than those obtained at the dissolved CO(2) concentration of 8.74 mM. It was also found that the additional CO(2) source provided in the form of NaHCO(3), MgCO(3), or CaCO(3) had positive effects on cell growth and succinic acid production. However, growth inhibition was observed when excessive bicarbonate salts were added. By the comparison of the activities of key enzymes, it was found that PEP carboxylation by PEP carboxykinase (PckA) is the most important for succinic acid production as well as the growth of M. succiniciproducens by providing additional ATP. PMID:17570706

  2. In Vitro Inhibition of Chick Embryo Lysyl Hydroxylase by Homogentisic Acid

    PubMed Central

    Murray, John C.; Lindberg, Kenneth A.; Pinnell, Sheldon R.

    1977-01-01

    Homogentisic acid inhibits the in vitro activity of chick embryo lysyl hydroxylase, a microsomal enzyme which catalyzes the transformation of certain lysyl residues in collagen to hydroxylysine. Chick embryo lysyl hydroxylase activity was measured as specific tritium release as tritium water from a [4,5-3H]lysine-labeled unhydroxylated collagen substrate prepared from chick calvaria. Kinetic studies revealed a linear, noncompetitive type of inhibition with respect to collagen substrate with a Ki of 120-180 ?M. The inhibition by homogentisic acid was reversible in that enzyme activity could be restored after dialysis of preincubated mixtures of homogentisic acid with enzyme or substrate. The inhibition by homogentisic acid was competitive with respect to ascorbic acid, and the addition of reducing agents, such as ascorbic acid or 1,4-dithiothreitol, protected lysyl hydroxylase activity from homogentisic acid inhibition. In organ cultures of embryonic chick calvaria, biosynthesis of hydroxylysine-derived intermolecular collagen cross-links was inhibited in a dose-dependent manner by 0.5-5 mM homogentisic acid. Because homogentisic acid inhibits the formation of hydroxylysine in a cell-free assay and in organ cultures, this compound must pass into the cells of calvaria to inhibit intracellular hydroxylysine formation and subsequently to diminish the reducible intermolecular cross-links of the newly synthesized collagen. We propose that the inhibition of lysyl hydroxylase and the resulting hydroxylsine-deficient, structurally modified collagen may be clinically significant in the defective connective tissue found in alkaptonuric patients. PMID:405402

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  4. Growth Suppression of Pre-T Acute Lymphoblastic Leukemia Cells by Inhibition of Notch Signaling

    PubMed Central

    Weng, Andrew P.; Nam, Yunsun; Wolfe, Michael S.; Pear, Warren S.; Griffin, James D.; Blacklow, Stephen C.; Aster, Jon C.

    2003-01-01

    Constitutive NOTCH signaling in lymphoid progenitors promotes the development of immature T-cell lymphoblastic neoplasms (T-ALLs). Although it is clear that Notch signaling can initiate leukemogenesis, it has not previously been established whether continued NOTCH signaling is required to maintain T-ALL growth. We demonstrate here that the blockade of Notch signaling at two independent steps suppresses the growth and survival of NOTCH1-transformed T-ALL cells. First, inhibitors of presenilin specifically induce growth suppression and apoptosis of a murine T-ALL cell line that requires presenilin-dependent proteolysis of the Notch receptor in order for its intracellular domain to translocate to the nucleus. Second, a 62-amino-acid peptide derived from a NOTCH coactivator, Mastermind-like-1 (MAML1), forms a transcriptionally inert nuclear complex with NOTCH1 and CSL and specifically inhibits the growth of both murine and human NOTCH1-transformed T-ALLs. These studies show that continued growth and survival of NOTCH1-transformed lymphoid cell lines require nuclear access and transcriptional coactivator recruitment by NOTCH1 and identify at least two steps in the Notch signaling pathway as potential targets for chemotherapeutic intervention. PMID:12509463

  5. 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 ...

  6. Choline inhibition of amino acid transport in preimplantation mouse blastocysts

    SciTech Connect

    Campione, A.L.; Haghighat, N.; Gorman, J.; Van Winkle, L.J.

    1987-05-01

    Addition of 70 mM choline chloride to Brinster's medium (140 mM Na/sup +/) inhibited uptake of approx. 1 ..mu..M (/sup 3/H)glycine, leucine, lysine and alanine in blastocysts by about 50% each during a five-minute incubation period at 37/sup 0/C, whereas 70 mM LiCl, sodium acetate and NaCl or 140 mM mannitol had no effect. They attribute the apparent linear relationship between Gly transport in blastocysts and the square of the (Na/sup +/), observed when choline was substituted for Na/sup +/ in Brinster's medium, to concomitant, concentration-dependent enhancement and inhibition of transport by Na/sup +/ and choline, respectively. As expected, Gly uptake and the (Na/sup +/) were linearly related up to 116 mM Na/sup +/, when Na/sup +/ was replaced with Li/sup +/. The rates of Na/sup +/-independent Gly and Ala uptake were <5% and <2% of the total, respectively, and similar when either Li/sup +/ or choline replaced Na/sup +/. Therefore, neither Li/sup +/ nor choline appears to substitute for Na/sup +/ in supporting Na/sup +/-dependent transport in blastocysts. Na/sup +/-independent Leu uptake was 20 times faster than Gly or Ala uptake and appeared to be inhibited by choline in blastocysts since it was about 37% slower when choline instead of Li/sup +/ was substituted for Na/sup +/. In contrast to blastocysts, choline had no effect on amino acid transport in cleavage-stage mouse embryos. The unexpected sensitivity of transport to choline in blastocysts underscores the importance of testing the effects of this substance when it is used to replace Na/sup +/ in new transport studies.

  7. Organic acids induce tolerance to zinc- and copper-exposed fungi under various growth conditions.

    PubMed

    Sazanova, Katerina; Osmolovskaya, Natalia; Schiparev, Sergey; Yakkonen, Kirill; Kuchaeva, Ludmila; Vlasov, Dmitry

    2015-04-01

    Heavy metals, Zn and Cu, in high concentration (2 mM for Zn and 0.5 mM for Cu) have some inhibiting effect on the growth of Aspergillus niger and Penicillium citrinum. Toxic effects of these metals considerably depend on cultivation conditions including nitrogen sources, pH of nutrient media, and its consistency (presence or absence of agar). In general, nitrate media provides less inhibiting effect on fungal growth under heavy metal exposure than ammonium-containing media. Adding of Zn in nitrate media induces oxalic acid production by fungi. Importance of oxalic acid production in detoxification of heavy metals is confirmed by the formation of Zn-containing crystals in fungal cultures. Cu bringing to the cultural media had no stimulating effect on oxalic acid production as well as no copper-containing crystals were observed. But proceeding from essential increase in oxalic acid production during a long-term fungi adaptation to Cu, it may be proposed that oxalic acid plays some functional role in Cu tolerance of fungi as well. It may be concluded that the role of organic acids and oxalate, in particular, in fungi tolerance and adaptation to heavy metals can be determined by the nature of the metal and its ability to form stable complexes with an acid anion. Stimulating effect of metals on acid production is not universal for all species of fungi and largely depends on metal concentration, nitrogen form in a medium, and other cultivation conditions. PMID:25502541

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  10. Luteolin Inhibits Human Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis

    PubMed Central

    Pratheeshkumar, Poyil; Son, Young-Ok; Budhraja, Amit; Wang, Xin; Ding, Songze; Wang, Lei; Hitron, Andrew; Lee, Jeong-Chae; Kim, Donghern; Divya, Sasidharan Padmaja; Chen, Gang; Zhang, Zhuo; Luo, Jia; Shi, Xianglin

    2012-01-01

    Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) and matrigel plug assay. Gelatin zymographic analysis demonstrated the inhibitory effect of luteolin on the activation of matrix metalloproteinases MMP-2 and MMP-9. Western blot analysis showed that luteolin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT, ERK, mTOR, P70S6K, MMP-2, and MMP-9 in HUVECs. Proinflammatory cytokines such as IL-1?, IL-6, IL-8, and TNF-? level were significantly reduced by the treatment of luteolin in PC-3 cells. Luteolin (10 mg/kg/d) significantly reduced the volume and the weight of solid tumors in prostate xenograft mouse model, indicating that luteolin inhibited tumorigenesis by targeting angiogenesis. CD31 and CD34 immunohistochemical staining further revealed that the microvessel density could be remarkably suppressed by luteolin. Moreover, luteolin reduced cell viability and induced apoptosis in prostate cancer cells, which were correlated with the downregulation of AKT, ERK, mTOR, P70S6K, MMP-2, and MMP-9 expressions. Taken together, our findings demonstrate that luteolin inhibits human prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. PMID:23300633

  11. Effects of amino acids, nitrate, and ammonium on the growth and taxol production in cell cultures of Taxus yunnanensis

    Microsoft Academic Search

    Yong-Qin Chen; Fei Yi; Min Cai; Jian-Xin Luo

    2003-01-01

    The effects of concentration of amino acids, nitrate, and ammonium on the growth and taxol production in cultures of cell line TY-21 of Taxus yunnanensis were investigated. Addition of 20 different amino acids each at 15–20 mg l-1 to B5 medium significantly improved callus growth but inhibited taxol formation in the cultures. The optimum nitrate concentration was 20–30 mM for

  12. Combined MET inhibition and topoisomerase I inhibition block cell growth of small cell lung cancer.

    PubMed

    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

    2014-03-01

    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

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

    PubMed Central

    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

    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

  14. Growth Inhibition of Listeria monocytogenes, Salmonella enterica, and Escherichia coli O157:H7 by D-Tryptophan as an Incompatible Solute.

    PubMed

    Koseki, Shigenobu; Nakamura, Nobutaka; Shiina, Takeo

    2015-04-01

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

  15. Growth inhibition of metronidazole-susceptible and metronidazole-resistant strains of Gardnerella vaginalis by Lactobacilli in vitro.

    PubMed Central

    McLean, N W; McGroarty, J A

    1996-01-01

    Metronidazole resistance was produced in susceptible Gardnerella vaginalis after subculture in the presence of metronidazole. Metronidazole-resistant gardnerellae were less susceptible to growth inhibition by Lactobacillus culture filtrates. A low pH (+/- 4) and lactic acid accounted for 60 to 95% of inhibitory activity, and H2O2 accounted for only 0 to 30%. However, in the presence of myeloperoxidase, H2O2-producing lactobacilli decreased the viability of metronidazole-susceptible gardnerellae 2,000-fold. PMID:8975601

  16. Inhibition of growth and induction of differentiation markers by polyphenolic molecules and histone deacetylase inhibitors in colon cancer cells.

    PubMed

    Lea, Michael A; Ibeh, Chinwe; Han, Lydia; Desbordes, Charles

    2010-02-01

    Previously we found that a fruit-derived polyphenol fraction caused an inhibition of proliferation and an induction of differentiation markers in Caco-2 human colon cancer cells. In the present work, we sought to determine if individual polyphenols would exert similar actions. Proliferation was inhibited by several polyphenolic molecules including gallic acid, ellagic acid, quercetin and resveratrol. In Caco-2 cells, growth inhibition was accompanied by increased specific activities of two differentiation markers, alkaline phosphatase and dipeptidyl peptidase, but not of aminopeptidase. Increased enzyme activities were not seen in HT29 and SW1116 colon cancer cells. In Caco-2 cells there were additive effects of butyrate or valproate and polyphenolic molecules. Histone acetylation was not greatly affected by the polyphenols. Cycloheximide inhibited protein synthesis in the 3 cell types examined but paradoxically, in Caco-2 cells it caused increased specific activities of alkaline phosphatase and dipeptidyl peptidase. Several plant polyphenols can inhibit the growth of colon cancer cells but increased specific activity of some differentiation markers seen in Caco-2 cells did not appear to be a general phenomenon in colon cancer cells. PMID:20332434

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

    SciTech Connect

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

    2012-07-13

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

  18. L-pyroglutamate spontaneously formed from L-glutamate inhibits growth of the hyperthermophilic archaeon Sulfolobus solfataricus.

    PubMed

    Park, C B; Lee, S B; Ryu, D D

    2001-08-01

    Identification of physiological and environmental factors that limit efficient growth of hyperthermophiles is important for practical application of these organisms to the production of useful enzymes or metabolites. During fed-batch cultivation of Sulfolobus solfataricus in medium containing L-glutamate, we observed formation of L-pyroglutamic acid (PGA). PGA formed spontaneously from L-glutamate under culture conditions (78 degrees C and pH 3.0), and the PGA formation rate was much higher at an acidic or alkaline pH than at neutral pH. It was also found that PGA is a potent inhibitor of S. solfataricus growth. The cell growth rate was reduced by one-half by the presence of 5.1 mM PGA, and no growth was observed in the presence of 15.5 mM PGA. On the other hand, the inhibitory effect of PGA on cell growth was alleviated by addition of L-glutamate or L-aspartate to the medium. PGA was also produced from the L-glutamate in yeast extract; the PGA content increased to 8.5% (wt/wt) after 80 h of incubation of a yeast extract solution at 78 degrees C and pH 3.0. In medium supplemented with yeast extract, cell growth was optimal in the presence of 3.0 g of yeast extract per liter, and higher yeast extract concentrations resulted in reduced cell yields. The extents of cell growth inhibition at yeast extract concentrations above the optimal concentration were correlated with the PGA concentration in the culture broth. Although other structural analogues of L-glutamate, such as L-methionine sulfoxide, glutaric acid, succinic acid, and L-glutamic acid gamma-methyl ester, also inhibited the growth of S. solfataricus, the greatest cell growth inhibition was observed with PGA. We also observed that unlike other glutamate analogues, N-acetyl-L-glutamate enhanced the growth of S. solfataricus. This compound was stable under cell culture conditions, and replacement of L-glutamate with N-acetyl-L-glutamate in the medium resulted in increased cell density. PMID:11472943

  19. Amino acid inhibition and stimulation of 2-aminoisobutyric acid exit from anuran small intestine

    PubMed Central

    Boyd, C. A. R.; Perring, Vivien S.

    1982-01-01

    1. Using the vascularly perfused frog small intestine, the exit of the non-metabolized amino acid 2-aminoisobutyric acid (AIB) from the pre-loaded epithelium into the blood has been studied in winter animals. 2. Marked inhibition of the instantaneous rate constant for AIB exit into the vascular bed is observed when L-leucine, but not D-leucine, is added either to the intestinal lumen or to the vascular bed. The extent of the inhibition is related to the leucine concentration in an alinear fashion. The concentration of luminal L-leucine giving half maximal inhibition is 2·5 mM. 3. The instantaneous rate constant for AIB exit is similarly decreased by 10 mM-L-tryptophan and by L-phenylalanine added to the intestinal lumen and to a lesser extent by L-asparagine, L-valine, L-glutamine, L-isoleucine, and L-norleucine. 4. 10 mM-L-proline added to the lumen stimulates AIB exit from the pre-loaded epithelium into the blood. This stimulation is due to an increased rate constant for movement of AIB across the basolateral membrane. 5. No inhibition is found when the dipeptide L-leucyl-L-leucine (10 mM) is added to the intestinal lumen in the presence of 10 mM-L-leucine. When added to the vascular compartment this dipeptide has no effect upon AIB exit from the epithelium. 6. Possible mechanisms by which amino acids and peptides may influence AIB movement out of the epithelium into the blood are discussed and conclusions are drawn concerning AIB transport across the intestinal basolateral membrane of the intact epithelium. PMID:7120150

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

    E-print Network

    Ouellette, Anthony J. A.

    species of algae that are affixed to a surface for most of their life cycle, propagating themselvesPhotocatalytic Inhibition of Algae Growth Using TiO2, WO3, and Cocatalyst Modifications C L O V I as photocatalytic surfacing agents to inhibit the attachment and growth of Oedogonium, a sessile, filamentous algae

  1. Intracellular acidification as a mechanism for the inhibition by acid hydrolysis-derived inhibitors of xylose fermentation by yeasts

    Microsoft Academic Search

    E M Lohmeier-Vogel; C R Sopher; H Lee

    1998-01-01

      The main degradation products (furfural, hydroxymethylfurfural, acetate) derived from acid hydrolysis of hemicellulosic materials\\u000a inhibit growth on and fermentation of xylose by Pachysolen tannophilus and Pichia stipitis, with the latter yeast being the more sensitive. The inhibitory effect was more severe when the inhibitors were present together\\u000a in the medium. Agarose immobilization partially protected the yeasts from the deleterious effects

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

    Microsoft Academic Search

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

    2009-01-01

    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

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

    E-print Network

    Levin, Judith G.

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

  4. Ascorbic Acid Inhibition of Candida albicans Hsp90-Mediated Morphogenesis Occurs via the Transcriptional Regulator Upc2

    PubMed Central

    Van Hauwenhuyse, Frédérique; Fiori, Alessandro

    2014-01-01

    Morphogenetic transitions of the opportunistic fungal pathogen Candida albicans are influenced by temperature changes, with induction of filamentation upon a shift from 30 to 37°C. Hsp90 was identified as a major repressor of an elongated cell morphology at low temperatures, as treatment with specific inhibitors of Hsp90 results in elongated growth forms at 30°C. Elongated growth resulting from a compromised Hsp90 is considered neither hyphal nor pseudohyphal growth. It has been reported that ascorbic acid (vitamin C) interferes with the yeast-to-hypha transition in C. albicans. In the present study, we show that ascorbic acid also antagonizes the morphogenetic change caused by hampered Hsp90 function. Further analysis revealed that Upc2, a transcriptional regulator of genes involved in ergosterol biosynthesis, and Erg11, the target of azole antifungals, whose expression is in turn regulated by Upc2, are required for this antagonism. Ergosterol levels correlate with elongated growth and are reduced in cells treated with the Hsp90 inhibitor geldanamycin (GdA) and restored by cotreatment with ascorbic acid. In addition, we show that Upc2 appears to be required for ascorbic acid-mediated inhibition of the antifungal activity of fluconazole. These results identify Upc2 as a major regulator of ascorbic acid-induced effects in C. albicans and suggest an association between ergosterol content and elongated growth upon Hsp90 compromise. PMID:25084864

  5. Epigenetic upregulation of Bak by ZBP-89 inhibits the growth of hepatocellular carcinoma.

    PubMed

    Ye, Cai Guo; Chen, George G; Ho, Rocky L K; Merchant, Juanita L; He, Ming-Liang; Lai, Paul B S

    2013-12-01

    Zinc-binding protein-89 regulates Bak to facilitate apoptosis in cancer cells. This study examined if zinc-binding protein-89 regulates Bak through an epigenetic mechanism in hepatocellular carcinoma. We first demonstrated that the expression of Bak was reduced but the levels of deoxyribonucleic acid methyltransferase 1 and histone deacetylase 3 were increased in hepatocellular carcinoma cancer tissues compared to the corresponding non-cancer tissues. Moreover, there was a negative correlation between Bak expression and deoxyribonucleic acid methyltransferase 1 levels in hepatocellular carcinoma. Administration of zinc-binding protein-89 downregulated histone deacetylase 3 expression and suppressed the activities of histone deacetylase and deoxyribonucleic acid methyltransferase, which led to maintenance of histone acetylation status, inhibited the binding of methyl-CpG-binding protein 2 to genomic deoxyribonucleic acid and demethylated CpG islands in the Bak promoter in hepatocellular carcinoma cells. Using the xenograft mouse tumor model, we demonstrated that zinc-binding protein-89 or inhibitors of either epigenetic enzymes could stimulate Bak expression, induce apoptosis, and arrest tumor growth and that the maximal effort was achieved when zinc-binding protein-89 and the enzyme inhibitors were used in combination. Conclusively, zinc-binding protein-89 upregulates the expression of Bak by targeting multiple components of the epigenetic pathway in hepatocellular carcinoma. PMID:23954442

  6. Effect of nerve growth factor and fibroblast growth factor on PC12 cells: inhibition by orthovanadate

    PubMed Central

    1993-01-01

    Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, causes increased levels of tyrosine phosphorylation and blocks, at noncytotoxic concentrations, the differentiative response of rat pheochromocytoma (PC12) cells to beta-nerve growth factor (beta NGF) and basic fibroblast growth factor (bFGF) in a reversible manner. It also prevents growth factor-induced neurite proliferation in primed cells and causes the retraction of previously formed neurites, even in the presence of beta NGF or bFGF. It is equally effective in blocking neurite proliferation by 8-Br-cAMP. Zinc chloride and ammonium molybdate, two other inhibitors of tyrosine phosphatases, also cause parallel decreases in neurite proliferation. Orthovanadate generally reduces the transcription of immediate early response genes (TIS 8 and c-fos) and secondary response genes (ornithine decarboxylase (ODC), acetyl-cholinesterase (AChE) and SCG 10) induced by beta NGF, bFGF, EGF, and PMA, albeit in a variable fashion. There was no observed effect on the kinetics of expression as judged by TIS 8 induction by beta NGF and protein kinase C (PKC) downregulation did not change the levels of inhibition by orthovanadate seen in control cells. Orthovanadate does not affect the production of diacylglycerol induced by beta NGF or bFGF. These observations are consistent with the view that growth factor stimulation of differentiation in PC12 cells involves at least one other PKC independent pathway, and that cAMP and PMA (and their active analogs) activate tyrosine kinases (albeit probably secondarily), which are at least partially responsible for their actions. Although the exact site(s) of action of orthovanadate that lead to the inhibition of growth factor-induced neurite proliferation are unknown, the results presented suggest that it prolongs tyrosine phosphorylations by nonreceptor tyrosine kinases that act downstream from the receptor kinases. PMID:8468355

  7. ?-Lipoic acid-induced inhibition of proliferation and met phosphorylation in human non-small cell lung cancer cells.

    PubMed

    Michikoshi, Hiromitsu; Nakamura, Takahiro; Sakai, Katsuya; Suzuki, Yoshinori; Adachi, Eri; Matsugo, Seiichi; Matsumoto, Kunio

    2013-07-28

    ?-Lipoic acid (?-LA), a naturally occurring anti-oxidant and co-factor for metabolic enzymes, suppresses the growth of different types of tumor cells. The mechanisms that are responsible for these results, however, remain to be elucidated. In the present study, we investigated the effects of ?-LA on the proliferation and activation status of definitive receptor tyrosine kinases, epidermal growth factor receptor (EGFR) and Met/hepatocyte growth factor (HGF) receptor, in gefitinib-sensitive human non-small cell lung cancer cells harboring EGFRs with an activating mutation. The enantiomers R-?-LA and S-?-LA suppressed cell proliferation and increased the level of reactive oxygen species in HCC-827 and PC-9 human non-small cell lung cancer cells in an indistinguishable dose-dependent fashion. A phospho-receptor tyrosine kinase array and cell cycle analysis indicated that ?-LA decreased tyrosine phosphorylation levels of EGFR, ErbB2, and Met, and this was associated with an inhibition in the cell-cycle transition from the G1 phase to the S phase without inducing apoptosis. Gefitinib, an inhibitor for EGFR tyrosine kinase, inhibited EGFR tyrosine phosphorylation/activation and proliferation of the cells. Instead, the addition of HGF induced Met tyrosine phosphorylation, and this was associated with a resistance to gefitinib-induced growth inhibition, which meant a gain in proliferative ability. In the presence of gefitinib and HGF, the addition of ?-LA suppressed Met tyrosine phosphorylation, and this was associated with an inhibition in cell growth. These results suggest that the suppression of tyrosine phosphorylation/activation of growth factor receptors that is critical for the proliferation of human non-small cell lung cancer cells is a mechanism by which ?-LA exerts growth inhibition for cancer cells. PMID:23507559

  8. Inhibition of acidic corrosion of pure aluminum by some organic compounds

    Microsoft Academic Search

    A. K. Maayta; N. A. F. Al-Rawashdeh

    2004-01-01

    Inhibition of the corrosion of aluminum (Al) in hydrochloric acid (HCl) by sulfonic acid (SA), sodium cumene sulfonate (SCS), and sodium alkyl sulfate (SAS) has been studied using weight-loss and potentiostatic polarization methods. The results drawn from the two techniques are comparable and exhibit small discrepancy. The inhibition action depends on the chemical structure and the concentration of the inhibitors,

  9. 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...

  10. Mechanisms of fatty acid-induced inhibition of glucose uptake.

    PubMed Central

    Boden, G; Chen, X; Ruiz, J; White, J V; Rossetti, L

    1994-01-01

    Increased plasma FFA reduce insulin-stimulated glucose uptake. The mechanisms responsible for this inhibition, however, remain uncertain. It was the aim of this study to determine whether the FFA effect was dose dependent and to investigate its mechanism. We have examined in healthy volunteers (13 male/1 female) the effects of three steady state plasma FFA levels (approximately 50, approximately 550, approximately 750 microM) on rates of glucose uptake, glycolysis (both with 3-3H-glucose), glycogen synthesis (determined with two independent methods), carbohydrate (CHO) oxidation (by indirect calorimetry), hepatic glucose output, and nonoxidative glycolysis (glycolysis minus CHO oxidation) during euglycemic-hyperinsulinemic clamping. Increasing FFA concentration (from approximately 50 to approximately 750 microM) decreased glucose uptake in a dose-dependent fashion (from approximately 9 to approximately 4 mg/kg per min). The decrease was caused mainly (approximately 2/3) by a reduction in glycogen synthesis and to a lesser extent (approximately 1/3) by a reduction in CHO oxidation. We have identified two independent defects in glycogen synthesis. The first consisted of an impairment of muscle glycogen synthase activity. It required high FFA concentration (approximately 750 microM), was associated with an increase in glucose-6-phosphate, and developed after 4-6 h of fat infusion. The second defect, which preceded the glycogen synthase defect, was seen at medium (approximately 550 microM) FFA concentration, was associated with a decrease in muscle glucose-6-phosphate concentration, and was probably due to a reduction in glucose transport/phosphorylation. In addition, FFA and/or glycerol increased insulin-suppressed hepatic glucose output by approximately 50%. We concluded that fatty acids caused a dose-dependent inhibition of insulin-stimulated glucose uptake (by decreasing glycogen synthesis and CHO oxidation) and that FFA and/or glycerol increased insulin-suppressed hepatic glucose output and thus caused insulin resistance at the peripheral and the hepatic level. PMID:8200979

  11. Chinese medicinal herbs inhibit growth of murine renal cell carcinoma.

    PubMed

    Lau, B H; Ruckle, H C; Botolazzo, T; Lui, P D

    1994-01-01

    Tumors are known to produce factors suppressing immune functions. We previously showed that a murine renal cell carcinoma (Renca) suppressed macrophage function in vitro and that this suppression was abolished by co-incubation with extracts of two Chinese medicinal herbs. We now report that these phytochemicals are capable of inhibiting growth of Renca in vivo. BALB/c mice were transplanted intraperitoneally (IP) with 1-2 x 10(5) Renca cells. One day after tumor transplant, mice were randomized into two groups. One group was treated IP, daily for 10 days, with 100 microliters of phytochemicals containing 500 micrograms each of Astragalus membranaceus and Ligustrum lucidum, while the other group received saline as controls. A cure rate of 57% was obtained with these phytochemicals when the initial tumor load was 2 x 10(5), and 100% when the initial tumor load was 1 x 10(5). Additional experiments were performed to investigate the mechanisms involved in this protection. Splenic macrophages from tumor-bearing mice were shown to have depressed chemiluminescent oxidative burst activity, and this depression was restored with phytochemical treatment. Splenocytes from mice transplanted with Renca responded less favorably to interleukin-2 (IL-2) in generating lymphokine-activated killer (LAK) cells; again this depression was restored with phytochemical treatment. Our data suggest that these phytochemicals may have exerted their antitumor effects via augmentation of phagocyte and LAK cell activities. PMID:7812364

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

    PubMed

    Choudhury, Shuvasish; Sharma, Parul

    2014-12-01

    Chickpea (Cicer arietinum L.) roots were treated with aluminum (Al3+) in calcium chloride (CaCl2) solution (pH 4.7) and growth responses along with physiological and metabolic changes were investigated. Al3+ 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 Al3+ 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 Al3+ treated roots. The hematoxylin and Evans blue assay indicated significant (p ? 0.05) accumulation of Al3+ in the roots and loss of plasma membrane integrity respectively. The time-course evaluation of lipid peroxidation showed increase in malondialdehyde (MDA) after 12, 24 and 48 h of stress imposition. Al3+ 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 (1H) 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 Al3+ stress. The key differences that were observed include changes in energy metabolites. Accumulation of phenolic compounds suggested its possible role in Al3+ exclusion in roots during stress. The results suggested that Al3+ alters growth pattern in chickpea and induces reactive oxygen species (ROS) production that causes physiological and metabolic changes. PMID:25394801

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

    Microsoft Academic Search

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

    1997-01-01

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

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

    Microsoft Academic Search

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

    2003-01-01

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

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

    Microsoft Academic Search

    Deborah J. Durnam; Russell L. Jones

    1982-01-01

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

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

    PubMed

    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

    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

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

    PubMed Central

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

    2014-01-01

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

  18. Inhibition of potato sprout growth by carvone enantiomers and their bioconversion in sprouts

    Microsoft Academic Search

    K. OOSTERHAVENI; K. J. Hartmans; J. J. C. Scheffer

    1995-01-01

    Summary  The monoterpenes (R)-(?)-carvone and (S)-(+)-carvone inhibited sprout growth in a model system consisting of sprouts growing\\u000a from potato eye pieces. The sprout tissue was not necrotic after carvone treatment and the inhibition was reversible, since\\u000a after treatment the sprouts showed regrowth either by continued top growth or by branching. However, the effect of both isomers\\u000a on sprout growth differed, and

  19. Effect of humic acids on the inhibition of pea choline esterase and choline acyltransferase with malathion

    Microsoft Academic Search

    Rita Malini de Almeida; F. Pospíšil; Kv?ta Vacková; M. Kutá?ek

    1980-01-01

    Humic acids in a concentration of up to 100 ?g ml-1 affect the activity of choline esterase of pea only weakly during sinapin (choline ester of sinapic acid) hydrolysis. The\\u000a inhibition is stronger at higher concentrations. A similar course of inhibition with humic acids was also observed during\\u000a the synthesis of sinapin catalysed with choline acyltransferase present in the same

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

    PubMed

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

    2015-05-01

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

  1. Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer.

    PubMed

    Melisi, Davide; Caputo, Rosa; Damiano, Vincenzo; Bianco, Roberto; Veneziani, Bianca Maria; Bianco, A Raffaele; De Placido, Sabino; Ciardiello, Fortunato; Tortora, Giampaolo

    2005-12-01

    Biphosphonates (BPs) are widely used to inhibit osteoclastic activity in malignant diseases such as bone metastatic breast and prostate carcinoma. Recent studies reported that BPs could also cause a direct antitumor effect, probably due to their ability to interfere with several intracellular signalling molecules. The enzyme cyclooxygenase-2 (COX-2) and the epidermal growth factor receptor (EGFR) play an important role in the control of cancer cell growth and inhibitors of COX-2 and EGFR have shown antitumor activity in vitro and in vivo in several tumor types. We, and others, have previously shown that EGFR and COX-2 may be directly related to each other and that their selective inhibitors may have a cooperative effect. In the present study we have evaluated the combined effect of zoledronic acid, the most potent nitrogen-containing BP, with the COX-2 inhibitor SC-236 and the selective EGFR-tyrosine kinase inhibitor gefitinib, on breast and prostate cancer models in vitro and in xenografted nude mice. We show that combination of zoledronic acid with SC-236 and gefitinib causes a cooperative antitumor effect accompanied by induction of apoptosis and regulation of the expression of mitogenic factors, proangiogenic factors and cell cycle controllers both in vitro and in xenografted nude mice. The modulatory effect on protein expression and the inhibitory effect on tumor growth is much more potent when the three agents are used together. Since studies are ongoing to explore the antitumor effect of zoledronic acid, our results provide new insights into the mechanism of action of these agents and a novel rationale to translate this feasible combination treatment strategy into a clinical setting. PMID:16322342

  2. Tyr-94 phosphorylation inhibits pyruvate dehydrogenase phosphatase 1 and promotes tumor growth.

    PubMed

    Shan, Changliang; Kang, Hee-Bum; Elf, Shannon; Xie, Jianxin; Gu, Ting-Lei; Aguiar, Mike; Lonning, Scott; Hitosugi, Taro; Chung, Tae-Wook; Arellano, Martha; Khoury, Hanna J; Shin, Dong M; Khuri, Fadlo R; Boggon, Titus J; Fan, Jun

    2014-08-01

    Many cancer cells rely more on aerobic glycolysis (the Warburg effect) than mitochondrial oxidative phosphorylation and catabolize glucose at a high rate. Such a metabolic switch is suggested to be due in part to functional attenuation of mitochondria in cancer cells. However, how oncogenic signals attenuate mitochondrial function and promote the switch to glycolysis remains unclear. We previously reported that tyrosine phosphorylation activates and inhibits mitochondrial pyruvate dehydrogenase kinase (PDK) and phosphatase (PDP), respectively, leading to enhanced inhibitory serine phosphorylation of pyruvate dehydrogenase (PDH) and consequently inhibition of pyruvate dehydrogenase complex (PDC) in cancer cells. In particular, Tyr-381 phosphorylation of PDP1 dissociates deacetylase SIRT3 and recruits acetyltransferase ACAT1 to PDC, resulting in increased inhibitory lysine acetylation of PDHA1 and PDP1. Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients. Moreover, expression of a phosphorylation-deficient PDP1 Y94F mutant in cancer cells resulted in increased oxidative phosphorylation, decreased cell proliferation under hypoxia, and reduced tumor growth in mice. Together, our findings suggest that phosphorylation at different tyrosine residues inhibits PDP1 through independent mechanisms, which act in concert to regulate PDC activity and promote the Warburg effect. PMID:24962578

  3. Inhibition of bacterial growth under composite restorations following GLUMA pretreatment.

    PubMed

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

    1989-03-01

    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

  4. Gambogic acid induces apoptosis in diffuse large B-cell lymphoma cells via inducing proteasome inhibition.

    PubMed

    Shi, Xianping; Lan, Xiaoying; Chen, Xin; Zhao, Chong; Li, Xiaofen; Liu, Shouting; Huang, Hongbiao; Liu, Ningning; Zang, Dan; Liao, Yuning; Zhang, Peiquan; Wang, Xuejun; Liu, Jinbao

    2015-01-01

    Resistance to chemotherapy is a great challenge to improving the survival of patients with diffuse large B-cell lymphoma (DLBCL), especially those with activated B-cell-like DLBCL (ABC-DLBCL). Therefore it is urgent to search for novel agents for the treatment of DLBCL. Gambogic acid (GA), a small molecule derived from Chinese herb gamboges, has been approved for Phase II clinical trial for cancer therapy by Chinese FDA. In the present study, we investigated the effect of GA on cell survival and apoptosis in DLBCL cells including both GCB- and ABC-DLBCL cells. We found that GA induced growth inhibition and apoptosis of both GCB- and ABC-DLBCL cells in vitro and in vivo, which is associated with proteasome malfunction. These findings provide significant pre-clinical evidence for potential usage of GA in DLBCL therapy particularly in ABC-DLBCL treatment. PMID:25853502

  5. Contact Inhibition of Growth Described by a Multiphase and an Individual Cell-Based Models

    E-print Network

    Preziosi, Luigi

    Contact Inhibition of Growth Described by a Multiphase and an Individual Cell-Based Models J. Galle applying an individual based model and a continuum multiphase model to cell colony growth in vitro of view. 1 Introduction The growth of cell monolayers in vitro can be divided in three main phases

  6. Ethanol inhibition of yeast growth and fermentation: Differences in the magnitude and complexity of the effect

    Microsoft Academic Search

    S. W. Brown; S. G. Oliver; D. E. F. Harrison; R. C. Righelato

    1981-01-01

    The effect of ethanol on yeast growth and fermentation has been studied in two strains, NCYC479 (a commercial saké yeast) and 5D-cyc (a laboratory haploid strain). The effect of ethanol on growth was similar in the two strains. It showed complex kinetics which resulted from both the inhibition of the growth rate itself and also a reduction in cell viability.

  7. Isolation and Properties of a Bacterium Inhibiting the Growth of Gymnodinium nagasakiense

    Microsoft Academic Search

    Kimio Fukami; Atsushi Yuzawa; Toshitaka Nishijima; Yoshihiko Hat

    1992-01-01

    A bacterium 5N-3 possessing a remarkable inhibitory effect on the growth of Gymnodinium nagasakiense was isolated from Uranouchi Inlet, Kochi. This bacterium was tentatively identified as Flavobacterium sp. The growth inhibiting effect of 5N-3 on G. nagasakiense was drastic in particular when the alga was in the logarithmic growth phase, and cell density decreased to less than 1% of the

  8. Phytotoxicity of coloured substances: is Lemna Duckweed an alternative to the algal growth inhibition test?

    Microsoft Academic Search

    Michael Cleuvers; Hans-Toni Ratte

    2002-01-01

    Coloured substances cause problems when interpreting algal tests, because effects due to light absorption can interact with potential toxicity. The Lemna Duckweed growth inhibition test can complement the algal test, on condition that the test is performed on a black, not reflecting surface. On white surfaces, test solution colour can strongly impact Lemna growth. For example, average control sample growth

  9. Caffeic acid phenethyl ester inhibits liver fibrosis in rats

    PubMed Central

    Li, Mei; Wang, Xiu-Fang; Shi, Juan-Juan; Li, Ya-Ping; Yang, Ning; Zhai, Song; Dang, Shuang-Suo

    2015-01-01

    AIM: To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester (CAPE) in rats with liver fibrosis. METHODS: A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group (n = 10), a vehicle group (n = 10), a model group (n = 15), a vitamin E group (n = 10), and three CAPE groups (CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE (3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin (TBil), aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde (MDA), glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on ?-smooth muscle actin (?-SMA), a characteristic hallmark of activated hepatic stellate cells (HSCs), and NF-E2-related factor 2 (Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry. RESULTS: Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats (P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group (P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group (P < 0.05). Moreover, CAPE effectively inhibited ?-SMA expression while increasing Nrf2 expression compared to the model group (P < 0.01). CONCLUSION: The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by inhibiting oxidative stress. PMID:25852274

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2014-06-01

    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

  12. Flavonoids purified from Rhus verniciflua Stokes actively inhibit cell growth and induce apoptosis in human osteosarcoma cells.

    PubMed

    Jang, Hyon-Seok; Kook, Sung-Ho; Son, Young-Ok; Kim, Jong-Ghee; Jeon, Young-Mi; Jang, Yong-Suk; Choi, Ki-Choon; Kim, Ju; Han, Seong-Kyu; Lee, Kyung-Yeol; Park, Byung-Keon; Cho, Nam-Pyo; Lee, Jeong-Chae

    2005-11-30

    Many studies have suggested that dietary flavonoids are anticancer agents that induce the apoptosis of cancer cells. However, the effects of flavonoids on the induction of apoptosis in osteosarcoma cells are unclear. Previously, a flavonoid fraction, consisting mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein, herein named RCMF (the RVS chloroform-methanol fraction), was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS). This study evaluated the effects of RCMF on the proliferation and apoptosis using human osteosarcoma (HOS) cells. The mechanism of growth inhibition of the HOS cells by the flavonoid fraction, RCMF, was also assessed. The results demonstrated that RCMF exhibited sensitive growth inhibition and induced apoptosis in HOS cells. PARP cleavage was closely associated with the RCMF-induced apoptosis of the HOS cells. Furthermore, the activation of caspase 8 and Bax, the inhibition of Bcl-2 expression, and the release of cytochrome c are believed to be involved in the RCMF-mediated apoptosis. Collectively, these findings suggest that RCMF is an agent which may be capable of inducing sensitive growth inhibition and apoptosis in HOS cells. PMID:16213662

  13. Competitive inhibition of Listeria monocytogenes in ready-to-eat meat products by lactic acid bacteria.

    PubMed

    Amézquita, A; Brashears, M M

    2002-02-01

    Forty-nine strains of lactic acid bacteria (LAB), isolated from commercially available ready-to-eat (RTE) meat products, were screened for their ability to inhibit the growth of Listeria monocytogenes at refrigeration (5 degrees C) temperatures on agar spot tests. The three most inhibitory strains were identified as Pediococcus acidilactici, Lactobacillus casei, and Lactobacillus paracasei by 16S rDNA sequence analysis. Their antilisterial activity was quantified in associative cultures in deMan Rogosa Sharpe (MRS) broth at 5 degrees C for 28 days, resulting in a pathogen reduction of 3.5 log10 cycles compared to its initial level. A combined culture of these strains was added to frankfurters and cooked ham coinoculated with L. monocytogenes, vacuum packaged, and stored at 5 degrees C for 28 days. Bacteriostatic activity was observed in cooked ham, whereas bactericidal activity was observed in frankfurters. Numbers of L. monocytogenes were 4.2 to 4.7 log10 and 2.6 log10 cycles lower than controls in frankfurters and cooked ham, respectively, after the 28-day refrigerated storage. In all cases, numbers of LAB increased by only 1 log10 cycle. The strain identified as P. acidilactici was possibly a bacteriocin producer, whereas the antilisterial activity of the other two strains was due to the production of organic acids. There was no significant difference (P > 0.05) in the antilisterial activity detected in frankfurters whether the LAB strains were used individually or as combined cultures. Further studies over a 56-day period indicated no impact on the quality of the product. This method represents a potential antilisterial intervention in RTE meats, because it inhibited the growth of the pathogen at refrigeration temperatures without causing sensory changes. PMID:11848562

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

    PubMed

    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

    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

  15. Inhibition of glycogen phosphorylase (GP) by CP-91,149 induces growth inhibition correlating with brain GP expression.

    PubMed

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

    2003-09-12

    The role of glycogenolysis in normal and cancer cells was investigated by inhibiting glycogen phosphorylase (GP) with the synthetic inhibitor CP-91,149. A549 non-small cell lung carcinoma (NSCLC) cells express solely the brain isozyme of GP, which was inhibited by CP-91,149 with an IC(50) of 0.5 microM. When treated with CP-91,149, A549 cells accumulated glycogen with associated growth retardation. Treated normal skin fibroblasts also accumulated glycogen with G1-cell cycle arrest that was associated with inhibition of cyclin E-CDK2 activity. Overall, cells expressing high levels of brain GP were growth inhibited by CP-91,149 correlating with glycogen accumulation whereas cells expressing low levels of brain GP were not affected by the drug. Analyses of 59 tumor cell lines represented in the NCI drug screen identified that every cell line expressed brain GP but the profile was dominated by a few highly GP expressing cell lines with lower than mean GP-a enzymatic activities. The correlation program, COMPARE, identified that the brain GP protein measured in the NCI cell lines corresponded with brain GP mRNA expression, ADP-ribosyltransferase 3, and colony stimulating factor 2 receptor alpha in the 10,000 gene microarray database with similar correlation coefficients. These results suggest that brain GP is present in proliferating cells and that high protein levels correspond with the ability of CP-91,149 to inhibit cell growth. PMID:12943673

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

    SciTech Connect

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

    2012-09-01

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

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

    E-print Network

    Hammock, Bruce D.

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

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    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.

  19. Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids.

    PubMed

    Liang, T; Liao, S

    1992-07-15

    Human or rat microsomal 5 alpha-reductase activity, as measured by enzymic conversion of testosterone into 5 alpha-dihydrotestosterone or by binding of a competitive inhibitor, [3H]17 beta-NN-diethulcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one ([3H]4-MA) to the reductase, is inhibited by low concentrations (less than 10 microM) of certain polyunsaturated fatty acids. The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: gamma-linolenic acid greater than cis-4,7,10,13,16,19-docosahexaenoic acid = cis-6,9,12,15-octatetraenoic acid = arachidonic acid = alpha-linolenic acid greater than linoleic acid greater than palmitoleic acid greater than oleic acid greater than myristoleic acid. Other unsaturated fatty acids such as undecylenic acid, erucic acid and nervonic acid, are inactive. The methyl esters and alcohol analogues of these compounds, glycerols, phospholipids, saturated fatty acids, retinoids and carotenes were inactive even at 0.2 mM. The results of the binding assay and the enzymic assay correlated well except for elaidic acid and linolelaidic acid, the trans isomers of oleic acid and linoleic acid respectively, which were much less active than their cis isomers in the binding assay but were as potent in the enzymic assay. gamma-Linolenic acid had no effect on the activities of two other rat liver microsomal enzymes: NADH:menadione reductase and glucuronosyl transferase. gamma-Linolenic acid, the most potent inhibitor tested, decreased the Vmax. and increased Km values of substrates, NADPH and testosterone, and promoted dissociation of [3H]4-MA from the microsomal reductase. gamma-Linolenic acid, but not the corresponding saturated fatty acid (stearic acid), inhibited the 5 alpha-reductase activity, but not the 17 beta-dehydrogenase activity, of human prostate cancer cells in culture. These results suggest that unsaturated fatty acids may play an important role in regulating androgen action in target cells. PMID:1637346

  20. Molecular interaction of pinic acid with sulfuric acid: exploring the thermodynamic landscape of cluster growth.

    PubMed

    Elm, Jonas; Kurtén, Theo; Bilde, Merete; Mikkelsen, Kurt V

    2014-09-11

    We investigate the molecular interactions between the semivolatile ?-pinene oxidation product pinic acid and sulfuric acid using computational methods. The stepwise Gibbs free energies of formation have been calculated utilizing the M06-2X functional, and the stability of the clusters is evaluated from the corresponding ?G values. The first two additions of sulfuric acid to pinic acid are found to be favorable with ?G values of -9.06 and -10.41 kcal/mol. Addition of a third sulfuric acid molecule is less favorable and leads to a structural rearrangement forming a bridged sulfuric acid-pinic acid cluster. The involvement of more than one pinic acid molecule in a single cluster is observed to lead to the formation of favorable (pinic acid)2(H2SO4) and (pinic acid)2(H2SO4)2 clusters. The identified most favorable growth paths starting from a single pinic acid molecule lead to closed structures without the further possibility for attachment of either sulfuric acid or pinic acid. This suggests that pinic acid cannot be a key species in the first steps in nucleation, but the favorable interactions between sulfuric acid and pinic acid imply that pinic acid can contribute to the subsequent growth of an existing nucleus by condensation. PMID:24988284

  1. Carbonic anhydrase IX promotes tumour growth and necrosis in vivo and inhibition enhances anti-VEGF therapy

    PubMed Central

    McIntyre, Alan; Patiar, Shalini; Wigfield, Simon; Li, Ji-liang; Ledaki, Ioanna; Turley, Helen; Leek, Russell; Snell, Cameron; Gatter, Kevin; Sly, William S.; Vaughan-Jones, Richard D.; Swietach, Pawel; Harris, Adrian L.

    2012-01-01

    Purpose Bevacizumab, an anti-VEGFA antibody, inhibits the developing vasculature of tumours, but resistance is common. Antiangiogenic therapy induces hypoxia and we observed increased expression of hypoxia-regulated genes, including carbonic anhydrase IX (CAIX), in response to Bevacizumab treatment in xenografts. CAIX expression correlates with poor prognosis in most tumour types and with worse outcome in Bevacizumab-treated metastatic colorectal cancer patients, malignant astrocytoma and recurrent malignant glioma. Experimental Design We knocked-down CAIX expression by shRNA in a colon cancer (HT29) and a glioblastoma (U87) cell line which have high hypoxic-induction of CAIX, and over-expressed CAIX in HCT116 cells which has low CAIX. We investigated the effect on growth rate in 3D culture and in vivo, and examined the effect of CAIX knockdown in combination with Bevacizumab. Results CAIX expression was associated with increased growth rate in spheroids and in vivo. Surprisingly, CAIX expression was associated with increased necrosis and apoptosis in vivo and in vitro. We found that acidity inhibits CAIX activity over the pH range found in tumours (pK=6.84), and this may be the mechanism whereby excess acid self-limits the build-up of extracellular acid. Expression of another hypoxia inducible CA isoform, CAXII, was upregulated in 3D but not 2D culture in response to CAIX knockdown. CAIX knockdown enhanced the effect of Bevacizumab treatment, reducing tumour growth rate in vivo. Conclusion This work provides evidence that inhibition of the hypoxic adaptation to anti-angiogenic therapy enhances Bevacizumab treatment and highlights the value of developing small molecules or antibodies which inhibit CAIX for combination therapy. PMID:22498007

  2. Targeting NF-B pathway with an IKK2 inhibitor induces inhibition of multiple myeloma cell growth

    E-print Network

    Paris-Sud XI, Université de

    1 Targeting NF-B pathway with an IKK2 inhibitor induces inhibition of multiple myeloma cell growth derivative AS602868, on the in vitro growth of 14 human MM cell lines (HMCL) and primary cells from 13-dependent inhibition of MM cell growth, which is the result of a simultaneous induction of apoptosis and inhibition

  3. Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma

    PubMed Central

    Subramani, Ramadevi; Lopez-Valdez, Rebecca; Salcido, Alyssa; Boopalan, Thiyagarajan; Arumugam, Arunkumar; Nandy, Sushmita; Lakshmanaswamy, Rajkumar

    2014-01-01

    Pancreatic cancer is the only major cancer with very low survival rates (1%). It is the fourth leading cause of cancer-related death. Hyperactivated growth hormone receptor (GHR) levels have been shown to increase the risk of cancer in general and this pathway is a master regulator of key cellular functions like proliferation, apoptosis, differentiation, metastasis, etc. However, to date there is no available data on how GHR promotes pancreatic cancer pathogenesis. Here, we used an RNA interference approach targeted to GHR to determine whether targeting GHR is an effective method for controlling pancreatic cancer growth and metastasis. For this, we used an in vitro model system consisting of HPAC and PANC-1 pancreatic cancer cells lines. GHR is upregulated in both of these cell lines and silencing GHR significantly reduced cell proliferation and viability. Inhibition of GHR also reduced the metastatic potential of pancreatic cancer cells, which was aided through decreased colony-forming ability and reduced invasiveness. Flow cytometric and western blot analyses revealed the induction of apoptosis in GHR silenced cells. GHR silencing affected phosphatidylinositol 3 kinase/AKT, mitogen extracellular signal-regulated kinase/extracellular signal-regulated kinase, Janus kinase/signal transducers and activators of transcription and mammalian target of rapamycin signaling, as well as, epithelial to mesenchymal transition. Interestingly, silencing GHR also suppressed the expression of insulin receptor-? and cyclo-oxygenease-2. Altogether, GHR silencing controls the growth and metastasis of pancreatic cancer and reveals its importance in pancreatic cancer pathogenesis. PMID:25301264

  4. Antisense Inhibition of the Iron-Sulphur Subunit of Succinate Dehydrogenase Enhances Photosynthesis and Growth in Tomato via an Organic Acid–Mediated Effect on Stomatal Aperture[W][OA

    PubMed Central

    Araújo, Wagner L.; Nunes-Nesi, Adriano; Osorio, Sonia; Usadel, Björn; Fuentes, Daniela; Nagy, Réka; Balbo, Ilse; Lehmann, Martin; Studart-Witkowski, Claudia; Tohge, Takayuki; Martinoia, Enrico; Jordana, Xavier; DaMatta, Fábio M.; Fernie, Alisdair R.

    2011-01-01

    Transgenic tomato (Solanum lycopersicum) plants expressing a fragment of the Sl SDH2-2 gene encoding the iron sulfur subunit of the succinate dehydrogenase protein complex in the antisense orientation under the control of the 35S promoter exhibit an enhanced rate of photosynthesis. The rate of the tricarboxylic acid (TCA) cycle was reduced in these transformants, and there were changes in the levels of metabolites associated with the TCA cycle. Furthermore, in comparison to wild-type plants, carbon dioxide assimilation was enhanced by up to 25% in the transgenic plants under ambient conditions, and mature plants were characterized by an increased biomass. Analysis of additional photosynthetic parameters revealed that the rate of transpiration and stomatal conductance were markedly elevated in the transgenic plants. The transformants displayed a strongly enhanced assimilation rate under both ambient and suboptimal environmental conditions, as well as an elevated maximal stomatal aperture. By contrast, when the Sl SDH2-2 gene was repressed by antisense RNA in a guard cell–specific manner, changes in neither stomatal aperture nor photosynthesis were observed. The data obtained are discussed in the context of the role of TCA cycle intermediates both generally with respect to photosynthetic metabolism and specifically with respect to their role in the regulation of stomatal aperture. PMID:21307286

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

    PubMed

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

    2014-11-01

    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

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

    PubMed

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

    2010-07-01

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

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

    Microsoft Academic Search

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

    1994-01-01

    Type I polar stratospheric clouds (PSCs) are thought to nucleate and grow on stratospheric sulfate aerosols (SSAs). To model this system, thin sulfuric acid films were exposed to water and nitric acid vapors (1-3 [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

  8. Induction of apoptosis and inhibition of invasion in choriocarcinoma JEG-3 cells by ?-calendic acid and ?-calendic acid.

    PubMed

    Li, Qian; Wang, Han; Ye, Shuhong; Xiao, Shan; Xie, Yuping; Liu, Xiao; Wang, Jihui

    2013-10-01

    Alfa-calendic acid and ?-calendic acid, geometric and positional isomers of linolenic acid were previously shown to possess potent anticancer properties. In this study, we found that ?-calendic acid and ?-calendic acid could induce apoptosis and suppress invasion of human choriocarcinoma JEG-3 cells in vitro. Treatment with ?-calendic acid and ?-calendic acid significantly increased oxidative stress in human choriocarcinoma JEG-3 cells detected by the level of reactive oxygen species (ROS), lipid peroxidation production malondialdehyde (MDA), glutathione (GSH) and the effects of antioxidants NAC and ?-tocopherol. Furthermore, oxidative stress activated the phosphorylation of p38MAPK. SB203580, a selective p38MAPK inhibitor, blocked the apoptosis induced by ?-calendic acid and ?-calendic acid by upregulating Bcl-2/Bax ratio and inhibition of the activation of Caspase-3 and Caspase-9. SB20350 also partially abrogated the cell invasion effects of ?-calendic acid and ?-calendic acid. These results suggested that ?-calendic acid and ?-calendic acid induced apoptosis and inhibited invasion in JEG-3 cells by activation of oxidative stress pathways and subsequent activation of P38MAPK. PMID:24035100

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

    PubMed

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

    2015-05-01

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

  10. Epidermal growth factor (EGF) prevents methylprednisolone-induced inhibition of wound healing.

    PubMed

    Laato, M; Heino, J; Kähäri, V M; Niinikoski, J; Gerdin, B

    1989-10-01

    Subcutaneously implanted cylindrical hollow viscose cellulose sponges were used to study the effect of locally applied epidermal growth factor (EGF) on methylprednisolone-induced inhibition of granulation tissue formation in rats. In in vivo studies the sponges were treated immediately after implantation with a single injection of 2 mg (approximately 1.7 x 10(-3) M) of depot methylprednisolone or with its carrier solution only. Thereafter the implants were injected daily with 5 micrograms of EGF or with its carrier solution 0.1% albumin for 7 days. Methylprednisolone treatment decreased the accumulation of nucleic acids, collagen, and glycosaminoglycans in the developing granulation tissue. After daily injections of EGF the concentrations of these tissue components returned close to the control values. In cultures of rat granulation tissue fibroblasts, 10(-4) M and 10(-3)M methylprednisolone decreased collagen synthesis by 41 and 81% from the control level, respectively. In the presence of methylprednisolone EGF treatment could not increase collagen synthesis of fibroblasts. Methylprednisolone treatment resulted in a dose-dependent reduction in pro alpha 1(I) collagen mRNA levels, which was partially inhibited by low EGF concentrations (1 and 10 ng/ml). In the presence of methylprednisolone all concentrations of EGF increased fibronectin mRNA levels in a dose-dependent manner. It is concluded that EGF treatment can prevent the inhibitory effect of methylprednisolone on wound healing by stimulating fibroblast proliferation but does not stimulate collagen synthesis per cell. PMID:2475671

  11. Activation of cannabinoid receptor 1 inhibits increased bladder activity induced by nerve growth factor.

    PubMed

    Wang, Zun-Yi; Wang, Peiqing; Bjorling, Dale E

    2015-03-01

    Nerve growth factor (NGF) is an important mediator of inflammatory pain, in part by sensitizing afferent nerve fibers, and expression of NGF is increased during bladder inflammation. We investigated whether intravesical instillation of the selective cannabinoid receptor 1 (CB1) agonist arachidonyl-2'-chloroethylamide (ACEA) affects NGF-induced increased bladder activity in female C57BL/6J wild-type (WT) mice. We also examined the effects of intravesical NGF in female fatty acid amide hydrolase knock-out (FAAH KO) mice. We found that CB1 and tyrosine kinase A (trkA, the high-affinity NGF receptor) were present in L6 dorsal root ganglion (DRG) afferent neurons and in bladders of both genotypes. Intravesical NGF increased bladder activity that was inhibited by intravesical ACEA in WT mice. The inhibitory effects of ACEA were reversed by the selective CB1 antagonist AM 251. Intravesical NGF failed to affect bladder activity in FAAH KO mice, and treatment with AM251, restored the stimulatory effects of NGF on the bladder in FAAH KO mice. These results indicate that activation of CB1 inhibits increased bladder activity induced by NGF. PMID:25575795

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

    SciTech Connect

    Sandler, Charlotta [Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Helsinki (Finland); Joutsiniemi, Saima [Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Helsinki (Finland); Lindstedt, Ken A. [Wihuri Research Institute, Helsinki (Finland); Juutilainen, Timo [Department of Orthopedic Surgery, Helsinki University Central Hospital, Helsinki (Finland); Kovanen, Petri T. [Wihuri Research Institute, Helsinki (Finland); Eklund, Kari K. [Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Helsinki (Finland)]. E-mail: kari.eklund@hus.fi

    2006-08-18

    Synovial fibroblast is the key cell type in the growth of the pathological synovial tissue in arthritis. Here, we show that platelet-derived growth factor (PDGF) is a potent mitogen for synovial fibroblasts isolated from patients with rheumatoid arthritis. Inhibition of PDGF-receptor signalling by imatinib mesylate (1 {mu}M) completely abrogated the PDGF-stimulated proliferation and inhibited approximately 70% of serum-stimulated proliferation of synovial fibroblasts. Similar extent of inhibition was observed when PDGF was neutralized with anti-PDGF antibodies, suggesting that imatinib mesylate does not inhibit pathways other than those mediated by PDGF-receptors. No signs of apoptosis were detected in synovial fibroblasts cultured in the presence of imatinib. These results suggest that imatinib mesylate specifically inhibits PDGF-stimulated proliferation of synovial fibroblasts, and that inhibition of PDGF-receptors could represent a feasible target for novel antirheumatic therapies.

  13. Testosterone Inhibits Growth in Juvenile Male Eastern Fence Lizards (Sceloporus undulatus): Implications for Energy Allocation

    E-print Network

    Cox, Robert

    531 Testosterone Inhibits Growth in Juvenile Male Eastern Fence Lizards (Sceloporus undulatus/18/2004; Electronically Published 5/13/2005 ABSTRACT In the eastern fence lizard, Sceloporus undulatus, female

  14. 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...

  15. Alpha lipoic acid selectively inhibits proliferation and adhesion to fibronectin of v-H-ras-transformed 3Y1 cells.

    PubMed

    Yamasaki, Masao; Iwase, Masahiro; Kawano, Kazuo; Sakakibara, Yoichi; Suiko, Masahito; Nishiyama, Kazuo

    2012-05-01

    Here, we focused on the effects of racemic ?-lipoic acid on proliferation and adhesion properties of 3Y1 rat fibroblasts and the v-H-ras-transformed derivative, HR-3Y1-2 cells. Racemic ?-lipoic acid inhibited proliferation of HR-3Y1-2 but not 3Y1 cells at 0.3 and 1.0 mM. R-(+)-?-lipoic acid also inhibited proliferation of HR-3Y1-2 cells equivalent to that of racemic ?-lipoic acid. In addition, racemic ?-lipoic acid decreased intracellular reactive oxygen species levels in HR-3Y1 cells but not 3Y1 cells. Next, we evaluated the effects of racemic ?-lipoic acid on cell adhesion to fibronectin. The results indicated that racemic ?-lipoic acid decreased adhesive ability of HR-3Y1-2 cells to fibronectin-coated plates. As blocking antibody experiment revealed that ?1-integrin plays a key role in cell adhesion in this experimental system, the effects of racemic ?-lipoic acid on the expression of ?1-integrin were examined. The results indicated that racemic ?-lipoic acid selectively downregulated the expression of cell surface ?1-integrin expression in HR-3Y1-2 cells. Intriguingly, exogenous hydrogen peroxide upregulated cell surface ?1-integrin expression in 3Y1 cells. Taken together, these data suggest that reduction of intracellular reactive oxygen species levels by ?-lipoic acid could be an effective means of ameliorating abnormal growth and adhesive properties in v-H-ras transformed cells. PMID:22573927

  16. Sclareol modulates the Treg intra-tumoral infiltrated cell and inhibits tumor growth in vivo

    Microsoft Academic Search

    Shokoofe Noori; Zuhair M. Hassan; Mehdi Mohammadi; Zohre Habibi; Nooshin Sohrabi; Saeed Bayanolhagh

    2010-01-01

    A regulatory or suppressor T cell is functionally defined as a T cell that inhibits an immune response by influencing the activity of another cell type. On the other hand, Th1 cells express IFN-? and mediate cellular immunity.Sclareol exhibits growth inhibition and cytotoxic activity against a variety of human cancer cell lines. In the first set of experiments, Sclareol was

  17. N-acetylcysteine inhibits germination of conidia and growth of Aspergillus spp. and Fusarium spp.

    PubMed Central

    De Lucca, A J; Walsh, T J; Daigle, D J

    1996-01-01

    N-Acetylcysteine inhibited hyphal growth and germination of conidia of Aspergillus spp. and Fusarium spp. N-Acetylcysteine inhibited conidial germination as well as or better than L-cysteine. Cysteine-related compounds may provide a potential therapeutic strategy against agriculturally and medically important fungal pathogens. PMID:8723482

  18. The reversal of cycocel induced inhibition of radicle growth by L -triethylammonium iodide

    Microsoft Academic Search

    M. N. Tewari; K. L. Menabia; T. Fatima; S. Kathju

    1973-01-01

    The new growth promoter, N(2-acyl-l,3-indane dione) triethylammonium iodide (L-TEAI) enhanced the elongation of the seedlings\\u000a of cluster bean (Cyamopsis tetragonoloba (L.) Taub, belonging to familyPapilionaceae). When the two growth regulators, L-TEAI and cycocel were applied together, the cycocel induced inhibition of radicle elongation\\u000a was reversed, but it failed to reverse the inhibition of hypocotyl elongation.

  19. Contact-Dependent Growth Inhibition Causes Reversible Metabolic Downregulation in Escherichia coli

    Microsoft Academic Search

    S. K. Aoki; J. S. Webb; B. A. Braaten; D. A. Low

    2009-01-01

    Contact-dependent growth inhibition (CDI) is a mechanism identified in Escherichia coli by which bacteria expressing two-partner secretion proteins encoded by cdiA and cdiB bind to BamA in the outer membranes of target cells and inhibit their growth. A third gene in the cluster, cdiI, encodes a small protein that is necessary and sufficient to confer immunity to CDI, thereby preventing

  20. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol

    Microsoft Academic Search

    Yvette D. Burke; M. Jennifer Stark; Steven L. Roach; Stephanie E. Sen; Pamela L. Crowell

    1997-01-01

    Fruits and vegetables have protective effects against many human cancers, including pancreatic cancer. Isoprenoids are one\\u000a class of phytochemicals which have antitumor activity, but little is known about their effects on cancer of the pancreas.\\u000a We tested the hypothesis that isoprenoids would inhibit the growth of pancreatic tumor cells. Significant (60–90%) inhibition\\u000a of the anchorage-independent growth of human MIA PaCa2

  1. Somatostatin Analogues Inhibit Growth of Pancreatic Cancer by Stimulating Tyrosine Phosphatase

    Microsoft Academic Search

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

    1989-01-01

    Several analogues of somatostatin were examined in the Mia PaCa-2 human pancreatic cancer cell line for their ability to promote tyrosine phosphatase activity affecting the receptors for the epidermal growth factor. The inhibition of growth of the Mia PaCa-2 cells in culture was also evaluated to determine the mechanism of action of somatostatin analogues and their relative effectiveness in inhibiting

  2. Cytokinin Antagonizes Abscisic Acid-Mediated Inhibition of Cotyledon Greening by Promoting the Degradation of ABSCISIC ACID INSENSITIVE5 Protein in Arabidopsis1[C][W

    PubMed Central

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

    2014-01-01

    In higher plants, seed germination is followed by postgerminative growth. One of the key developmental events during postgerminative growth is cotyledon greening, which enables a seedling to establish photosynthetic capacity. The plant phytohormone abscisic acid (ABA) plays a vital role by inhibiting seed germination and postgerminative growth in response to dynamically changing internal and environmental cues. It has been shown that ABSCISIC ACID INSENSITIVE5 (ABI5), a basic leucine zipper transcription factor, is an important factor in the regulation of the ABA-mediated inhibitory effect on seed germination and postgerminative growth. Conversely, the phytohormone cytokinin has been proposed to promote seed germination by antagonizing the ABA-mediated inhibitory effect. However, the underpinning molecular mechanism of cytokinin-repressed ABA signaling is largely unknown. Here, we show that cytokinin specifically antagonizes ABA-mediated inhibition of cotyledon greening with minimal effects on seed germination in Arabidopsis (Arabidopsis thaliana). We found that the cytokinin-antagonized ABA effect is dependent on a functional cytokinin signaling pathway, mainly involved in the cytokinin receptor gene CYTOKININ RESPONSE1/ARABIDOPSIS HISTIDINE KINASE4, downstream histidine phosphotransfer protein genes AHP2, AHP3, and AHP5, and a type B response regulator gene, ARR12, which genetically acts upstream of ABI5 to regulate cotyledon greening. Cytokinin has no apparent effect on the transcription of ABI5. However, cytokinin efficiently promotes the proteasomal degradation of ABI5 in a cytokinin signaling-dependent manner. These results define a genetic pathway through which cytokinin specifically induces the degradation of ABI5 protein, thereby antagonizing ABA-mediated inhibition of postgerminative growth. PMID:24443524

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

    PubMed Central

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

    2013-01-01

    Investigation of the metabolome and the transcriptome of pollen of lily (Lilium longiflorum) gave a comprehensive overview of metabolic pathways active during pollen germination and tube growth. More than 100 different metabolites were determined simultaneously by gas chromatography coupled to mass spectrometry, and expressed genes of selected metabolic pathways were identified by next-generation sequencing of lily pollen transcripts. The time-dependent changes in metabolite abundances, as well as the changes after inhibition of the mitochondrial electron transport chain, revealed a fast and dynamic adaption of the metabolic pathways in the range of minutes. The metabolic state prior to pollen germination differed clearly from the metabolic state during pollen tube growth, as indicated by principal component analysis of all detected metabolites and by detailed observation of individual metabolites. For instance, the amount of sucrose increased during the first 60 minutes of pollen culture but decreased during tube growth, while glucose and fructose showed the opposite behavior. Glycolysis, tricarbonic acid cycle, glyoxylate cycle, starch, and fatty acid degradation were activated, providing energy during pollen germination and tube growth. Inhibition of the mitochondrial electron transport chain by antimycin A resulted in an immediate production of ethanol and a fast rearrangement of metabolic pathways, which correlated with changes in the amounts of the majority of identified metabolites, e.g. a rapid increase in ?-aminobutyric acid indicated the activation of a ?-aminobutyric acid shunt in the tricarbonic acid cycle, while ethanol fermentation compensated the reduced ATP production after inhibition of the oxidative phosphorylation. PMID:23660836

  4. Role of acids and bases in nanoparticle growth

    NASA Astrophysics Data System (ADS)

    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

    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.

  5. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles.

    PubMed

    Hannon, Patrick R; Brannick, Katherine E; Wang, Wei; Gupta, Rupesh K; Flaws, Jodi A

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1-100?g/ml) for 24-96h to establish the temporal effects of DEHP on the follicle. Following 24-96h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17?-hydroxylase-17,20-desmolase, 17?-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. PMID:25701202

  6. Mechanism of betulinic acid inhibition of collagen biosynthesis in human endometrial adenocarcinoma cells.

    PubMed

    Karna, E; Palka, J A

    2009-01-01

    Collagen as a ligand for integrin receptors plays important role in the integrin - dependent regulation of cellular metabolism. Since betulinic acid (BA) evokes anticancer activity, its effect on collagen biosynthesis was studied in cultured endometrial adenocarcinoma cells. Confluent cells were treated with different concentrations of BA for 24 hours. It was found that BA inhibit collagen biosynthesis ([3H] proline incorporation assay). The mechanism of this phenomenon was found at the level of insulin-like growth factor-I receptor (IGF-IR) and alpha2 integrin signalling (Western immunoblot analysis). The expressions of IGF-I receptor and alpha2 integrin subunit as well as integrin activated focal adhesion kinase (FAK) were decreased in the cells treated with BA. It was accompanied by a parallel decrease in the expression of Sos protein and phosphorylated MAP-kinases (ERK1, ERK2) and up - regulation of NF-kappaB. The data suggest that BA-dependent inhibition of collagen biosynthesis in cultured human endometrial adenocarcinoma cells undergoes through alpha2 integrin and IGF-IR signaling that activate NF-kappaB, potent inhibitor of collagen gene expression. PMID:19469659

  7. INHIBITING EFFECT OF CRYSTAL VIOLET DYE ON ALUMINUM CORROSION IN ACIDIC AND ALKALINE MEDIA

    Microsoft Academic Search

    Emeka E. Oguzie

    2008-01-01

    Crystal violet dye (CV) was studied as a corrosion inhibitor for aluminum in hydrochloric acid (1 mol dm) and potassium hydroxide (0.5 mol dm) solutions in the temperature range 30°–60°C using the gravimetric technique. The effect of iodide ions on the inhibiting efficacy of CV was also assessed. CV was found to inhibit Al corrosion in both aggressive media, exhibiting greater inhibition efficiency

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

    PubMed Central

    Zhang, Jingjie; Ouyang, Weiming; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui; Wang, York; Li, Xuejun; Huang, Chuanshu

    2013-01-01

    Suberoylanilide hydroxamic acid (SAHA) inhibiting cancer cell growth has been associated with its down-regulation 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. PMID:22749963

  9. Microencapsulation of tannic acid for oral administration to inhibit carbohydrate digestion in the gastrointestinal tract.

    PubMed

    Zhao, Wei; Iyer, Vidya; Flores, Floirendo P; Donhowe, Erik; Kong, Fanbin

    2013-06-01

    The prevalence of diabetes mellitus and obesity is rapidly rising worldwide. Recently, there is increasing evidence that phytochemicals such as polyphenols in our diet could directly inhibit the activities of key digestive enzymes, representing a novel method of controlling and preventing diabetes mellitus and obesity. More research is required to determine how to effectively utilize phytochemicals within the gastrointestinal (GI) tract to obtain maximum inhibition of digestive enzymes. This study investigated the inhibition efficiency of tannic acid (TA) on ?-amylase as compared with other potential inhibitors using an in vitro method. The inhibition mode and kinetics were studied. The results showed that tannic acid (TA) is more effective in inhibiting ?-amylase than a commercial starch blocker (Phase 2 Starch Blocker), and some selected flavonoids and polyphenols including quercetin, rutin, and polyphenon from green tea. It is also found that inhibition of ?-amylase by TA in the GI tract is difficult if administered orally due to the non-specific and reversible noncompetitive interaction between tannic acid and ?-amylase or other proteins. Accordingly, a pH-sensitive delivery system using calcium-alginate microspheres encapsulating tannic acid was successfully developed for oral administration to inhibit carbohydrate digestion in the GI tract. The encapsulated TA in calcium-alginate microspheres could be protected from the proteins in the stomach, and sustain release and inhibit ?-amylase activity in the small intestine. PMID:23648648

  10. PREPARATION, DRUG RELEASE, AND CELL GROWTH INHIBITION OF A GELATIN – DOXORUBICIN CONJUGATE

    PubMed Central

    Wu, Darren C.; Cammarata, Christopher R.; Park, Hyun Joo; Rhodes, Brian T.; Ofner, Clyde M.

    2013-01-01

    Purpose To demonstrate the feasibility of a novel macromolecular delivery system for doxorubicin (DOX) which combines pH dependent DOX release with a high molecular weight and biodegradable gelatin carrier. Methods DOX was conjugated to gelatin using an acid labile hydrazone bond and a glycylglycine linker. The gelatin-doxorubicin conjugate (G-DOX) was evaluated for hydrazide and DOX content by spectrophotometry, molecular weight by HPLC-SEC, in vitro DOX release at various pH, and cell growth inhibition using EL4 mouse lymphoma and PC3 human prostate cells. Results G-DOX hydrazide and DOX content was 47% and 5-7%, respectively of theoretical gelatin carboxylic acid sites. During preparation of G-DOX, the molecular weight decreased to 22 kDa. DOX release was 48% in pH 4.8 phosphate buffer, 22% at pH 6.5, but 10% at pH 7.4. The G-DOX IC50 values in EL4 and PC3 cells were 0.26 ?M and 0.77 ?M, respectively; the latter value 3 times greater than that of free DOX. Conclusions A 22 kDa macromolecular DOX conjugate containing 3.4-5.0% w/w DOX has been prepared. The pH dependent drug release in combination with a biodegradable gelatin carrier offer potential therapeutic advantages of enhanced tumor cell localization and reduced systemic toxicities of the drug. PMID:23686374

  11. Extract from Rhus verniciflua Stokes is capable of inhibiting the growth of human lymphoma cells.

    PubMed

    Lee, J-C; Lee, K-Y; Kim, J; Na, C-S; Jung, N-C; Chung, G-H; Jang, Y-S

    2004-09-01

    Rhus verniciflua Stokes (RVS), used as a food additive and a traditional herbal medicine, has both antioxidant and antitumor activities which are known to be closely associated with the polyphenolic compounds that it contains. In the present study, we purified a fraction from a crude acetone extract of RVS, named RCMF (RVS chloroform-methanol fraction), and evaluated its ability to scavenge free radicals and inhibit cell growth. In addition, the active compounds responsible for the activities were identified. Results showed that RCMF contained an antioxidant potential and strongly suppressed the proliferative capability of B lymphoma cells. RCMF-mediated suppression of cell growth was verified to be apoptotic, based on the increased DNA fragmentation and low fluorescence intensity in the nuclei after propidium iodide staining, and also on the appearance of DNA laddering. Finally, EI-MS, 1H-NMR, and 13C-NMR spectra confirmed that RCMF contained flavonoid derivatives, including protocatechuic acid, fustin, fisetin, sulfuretin, and butein, suggesting that these flavonoid derivatives are the main active compounds responsible for the antioxidant and antiproliferative activities of RCMF. PMID:15234068

  12. miR-29b represses intestinal mucosal growth by inhibiting translation of cyclin-dependent kinase 2

    PubMed Central

    Xiao, Lan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Cao, Shan; Martindale, Jennifer L.; Su, Weijie; Chung, Hee Kyoung; Gorospe, Myriam; Wang, Jian-Ying

    2013-01-01

    The epithelium of the intestinal mucosa is a rapidly self-renewing tissue in the body, and defects in the renewal process occur commonly in various disorders. microRNAs (miRNAs) posttranscriptionally regulate gene expression and are implicated in many aspects of cellular physiology. Here we investigate the role of miRNA-29b (miR-29b) in the regulation of normal intestinal mucosal growth and further validate its target mRNAs. miRNA expression profiling studies reveal that growth inhibition of the small intestinal mucosa is associated with increased expression of numerous miRNAs, including miR-29b. The simple systemic delivery of locked nucleic acid–modified, anti–miR-29b-reduced endogenous miR-29b levels in the small intestinal mucosa increases cyclin-dependent kinase 2 (CDK2) expression and stimulates mucosal growth. In contrast, overexpression of the miR-29b precursor in intestinal epithelial cells represses CDK2 expression and results in growth arrest in G1 phase. miR-29b represses CDK2 translation through direct interaction with the cdk2 mRNA via its 3?-untranslated region (3?-UTR), whereas point mutation of miR-29b binding site in the cdk2 3?-UTR prevents miR-29b–induced repression of CDK2 translation. These results indicate that miR-29b inhibits intestinal mucosal growth by repressing CDK2 translation. PMID:23904268

  13. Kinetic evaluation of products inhibition to succinic acid producers Escherichia coli NZN111, AFP111, BL21, and Actinobacillus succinogenes 130Z T

    Microsoft Academic Search

    Qiang Li; Dan Wang; Yong Wu; Maohua Yang; Wangliang Li; Jianmin Xing; Zhiguo Su

    2010-01-01

    Succinic acid is one of the platform compounds and its production via natural feedstocks has drawn worldwide concerns. To\\u000a evaluate the inhibitory effects of fermentation products on the growth of Actinobacillus succinogenes 130ZT and Escherichia coli NZN111, AFP111, BL21, fermentations with addition of individual products in medium were carried out. The cell growth was\\u000a inhibited when the concentrations of formate,

  14. Expression of the Type-1 Repeats of Thrombospondin-1 Inhibits Tumor Growth Through Activation of Transforming Growth Factor-?

    PubMed Central

    Yee, Karen O.; Streit, Michael; Hawighorst, Thomas; Detmar, Michael; Lawler, Jack

    2004-01-01

    In the present study, the type-1 repeats of thrombospondin-1 (TSP-1) were transfected into A431 cells. Expression of all three type-1 repeats (3TSR) and expression of just the second type-1 repeat containing the transforming growth factor (TGF)-? activating sequence KRFK (TSR2 + KRFK) significantly inhibited in vivo tumor angiogenesis and growth in nude mice. These tumors expressed increased levels of both active and total TGF-?. A431 cells expressing the second type-1 repeat without the KRFK sequence (TSR2 ? KRFK) produced tumors that were slightly larger than the 3TSR and TSR2 + KRFK tumors. These tumors expressed elevated levels of active TGF-? but levels of total TGF-? were not different from control tumors. Injection of the peptide, LSKL, which blocks TSP-1 activation of TGF-?, reversed the growth inhibition observed with cells expressing TSR2 + KRFK to a level comparable to controls. Various residues in the WSHWSPW region and the VTCG sequence of both TSR2+/? KRFK were mutated. Although mutation of the VTCG sequence had no significant effect on tumor growth, mutation of the WSHWSPW sequence reduced inhibition of tumor growth. These findings suggest that the inhibition of tumor angiogenesis and growth by endogenous TSP-1 involves regulation of both active and total TGF-? and the sequences KRFK and WSHWSPW in the second type-1 repeat. PMID:15277228

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

    PubMed Central

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

    2000-01-01

    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

  16. Inhibition of the growth and differentiation of erythroid precursor cells by an endotoxin-induced mediator from peritoneal macrophages.

    PubMed Central

    Sassa, S; Kawakami, M; Cerami, A

    1983-01-01

    Conditioned medium from cultures of mouse macrophages incubated with endotoxin in a serum-free medium contains an inhibitor of the growth and differentiation of erythroid precursor cells of mouse Friend virus-transformed erythroleukemia cells. Endotoxin itself has no inhibitory effect. The endotoxin-induced macrophage mediator inhibits the growth and differentiation of dimethyl sulfoxide-, hexamethylenebisacetamide-, butyric acid-, and hypoxanthine-induced cells but has no effect on hemin-induced cells. The conditioned medium has its maximal inhibitory effect on committed erythroid precursor cells, a decreased effect on uncommitted stem cells, and no effect on fully differentiated erythroid cells. These results demonstrate that endotoxin stimulation of macrophages leads to the production of a humoral factor(s) which is critical for the growth and differentiation of erythroid precursor cells. Images PMID:6572935

  17. 17?-estradiol, Progesterone, and Dihydrotestosterone Suppress the Growth of Human Melanoma by Inhibiting Interleukin8 Production

    Microsoft Academic Search

    Naoko Kanda; Shinichi Watanabe

    2001-01-01

    We studied the effects of 17?-estradiol, progesterone, and dihydrotestosterone on in vitro growth of human metastatic melanoma. Each sex hormone inhibited the growth of melanoma receptor-dependently; 17?-estradiol inhibited 3H-thymidine uptake of estrogen receptor-positive WM266-4 and NM26, but not that of the receptor-negative HS15. Progesterone inhibited 3H-thymidine uptake of progesterone receptor-positive WM266-4 and HS15, but not that of the receptor-negative NM26.

  18. Investigation of inhibition effect of some amino acids against steel corrosion in HCl solution

    NASA Astrophysics Data System (ADS)

    Ashassi-Sorkhabi, H.; Majidi, M. R.; Seyyedi, K.

    2004-03-01

    The inhibition effect of three amino acids against steel corrosion in HCl solutions has been investigated by potentiodynamic polarization method. Corrosion data such as corrosion rate, corrosion potential ( Ecorr) and corrosion resistance ( Rp) were determined by extrapolation of the cathodic and anodic Tafel region. Adsorption isotherm was investigated by weight-loss measurement. The used amino acids were alanine, glycine and leucine. The effect of inhibitor concentration and acid concentration against inhibitor action was investigated. The inhibition efficiency (IE) depended on the type of amino acid and its concentration. The inhibition effect ranged from 28 to 91%. The amino acids act as a corrosion inhibitor in HCl solution through adsorption on the steel surface and adsorption follows Langmuir isotherm.

  19. Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and inhibits choroidal neovascularization

    PubMed Central

    Huang, Jiahn-Dar; Amaral, Juan; Lee, Jung Wha; Larrayoz, Ignacio M.; Rodriguez, Ignacio R.

    2012-01-01

    Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer’s disease and age-related macular degeneration. Sterculic acid demonstrated to be 5–10 times more effective than other anti-inflammatory fatty acids at inhibiting 7KCh-mediated inflammatory responses in cultured cells. In vivo, sterculic acid was effective at inhibiting the formation of choroidal neovascularization (CNV) in the laser-injury rat model. Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration. PMID:22342272

  20. A ROLE FOR AMPK IN THE INHIBITION OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE BY POLYUNSATURATED FATTY ACIDS

    PubMed Central

    Kohan, Alison B.; Talukdar, Indrani; Walsh, Callee M.; Salati, Lisa M.

    2009-01-01

    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 ?-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 Ser307 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. PMID:19646964

  1. Inhibition of a ubiquitously expressed pectin methyl esterase in Solanum tuberosum L. affects plant growth, leaf growth polarity, and ion partitioning.

    PubMed

    Pilling, J; Willmitzer, L; Bücking, H; Fisahn, J

    2004-05-01

    Two pectin methyl esterases (PMEs; EC 3.1.1.11) from Solanum tuberosum were isolated and their expression characterised. One partial clone ( pest1) was expressed in leaves and fruit tissue, while pest2 was a functional full-length clone and was expressed ubiquitously, with a preference for aerial organs. Potato plants were transformed with a chimeric antisense construct that was designed to simultaneously inhibit pest1 and pest2 transcript accumulation; however, reduction of mRNA levels was confined to pest2. The decrease in pest2 transcript was accompanied by up to 50% inhibition of total PME activity, which was probably due to the reduction of only one PME isoform. PME inhibition affected plant development as reflected by smaller stem elongation rates of selected transformants when compared with control plants, leading to a reduction in height throughout the entire course of development. Expansion rates of young developing leaves were measured simultaneously by two displacement transducers in the direction of the leaf tip (proximal-distal axis) and in the perpendicular direction (medial-lateral axis). Significant differences in leaf growth patterns were detected between wild-type and transgenic plants. We suggest that these visual phenotypes could be correlated with modifications of ion accumulation and partitioning within the transgenic plants. The ion-binding capacities of cell walls from PME-inhibited plants were specifically modified as they preferentially bound more sodium, but less potassium and calcium. X-ray microanalysis also indicated an increase in the concentration of several ions within the leaf apoplast of transgenic plants. Moreover, quantification of the total content of major cations revealed differences specific for a given element between the leaves of PME-inhibited and wild-type plants. Reduced growth rates might also be due to effects of PME inhibition on pectin metabolism, predominantly illustrated by an accumulation of galacturonic acid over other cell wall components. PMID:14747949

  2. Calpain Inhibition Decreases the Growth Rate of Mammalian Cell Colonies*

    E-print Network

    Abraham, Nader G.

    of proliferative growth of mouse stem cells under routine culture conditions. To address the reasons of calpastatin in these cell lines resulted in a de- creased growth of isolated colonies adhering to tissue culture plates. However, when cells were plated at higher density, calpastatin overexpression had no influ

  3. Distinct sequence motifs within the cytoplasmic domain of the human IL-4 receptor differentially regulate apoptosis inhibition and cell growth.

    PubMed

    Deutsch, H H; Koettnitz, K; Chung, J; Kalthoff, F S

    1995-04-15

    Hematopoietin receptors generally function as multimeric complexes composed of a unique ligand-binding chain and a second component often shared between several members of this receptor family. To better understand the signal transduction of the human IL-4 receptor (hIL4R), we analyzed the functionality of targeted mutations in two cytoplasmic regions of the ligand-binding hIL4R chain that we previously identified to be necessary for growth mediation in factor-dependent murine Ba/F3 cells. Here, we provide evidence that transient inhibition of apoptotic death of Ba/F3 cells and the competence to proliferate indefinitely depend on separated and distinct sequence motifs of the hIL4R. In particular, hIL4R constructs with a truncation of the recently described gp130 box1 from P242 to K264, or a deletion of the acidic region between S330 and S365, fail to stimulate growth or to mediate the inhibition of apoptosis. hIL4R bearing a point mutation within the gp130 box1 (P242S) is defective for growth stimulation but still signals the transient inhibition of apoptotic cell death and the induction of c-myc RNA. A third region required for IL4-mediated cell growth is localized between T462 and S476 and includes the sequence NPAY previously described to serve as interaction motif in signaling of epidermal growth factor and insulin receptors. Conversion of Y472 into F472 within the latter hIL4R motif affects the competence of stably transfected BA/F3 cells to proliferate indefinitely in the presence of hIL4. Sequences C-terminal of S476 are not essential for growth stimulation of BA/F3 transfectants. PMID:7706712

  4. Growth Inhibition of Human Gynecologic and Colon Cancer Cells by Phyllanthus watsonii through Apoptosis Induction

    PubMed Central

    Ramasamy, Sujatha; Abdul Wahab, Norhanom; Zainal Abidin, Nurhayati; Manickam, Sugumaran; Zakaria, Zubaidah

    2012-01-01

    Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC50 values of ? 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1?PW-10). PW-4?PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1?PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC50 values ranged from 0.66 – 0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs. PMID:22536331

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

    PubMed Central

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

    2010-01-01

    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

  6. 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...

  7. Molecular mechanism of interferon alfa–Mediated growth inhibition in human neuroendocrine tumor cells

    Microsoft Academic Search

    Katharina M. Detjen; Martina Welzel; Katrin Farwig; Felix H. Brembeck; Astrid Kaiser; Ernst-Otto Riecken; Bertram Wiedenmann; Stefan Rosewicz

    2000-01-01

    Background & Aims: Although human neuroendocrine tumors respond to interferon (IFN)-? treatment in vivo, the underlying mechanisms of growth inhibition are poorly understood. To characterize the antiproliferative effects at a molecular level, we explored the growth-regulatory action of IFN-? in the human neuroendocrine tumor cell lines BON and QGP1. Methods: IFN-? receptor expression and signal transduction were examined by reverse-transcription

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

    Microsoft Academic Search

    Santos García; Ginebra Alarcón; Cristina Rodríguez; Norma Heredia

    2006-01-01

    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

  9. Unilateral vagotomy inhibits compensatory kidney growth after unilateral nephrectomy in rats.

    PubMed

    Gerendai, I; Nemeskéri, A; Halász, B

    1986-01-01

    The effect of unilateral vagotomy on compensatory renal growth that follows unilateral nephrectomy was studied. Unilateral vagotomy inhibited the usual compensatory growth of the remaining kidney. Unilateral vagotomy did not effect kidney weight in animals with two kidneys. Data indicate that the vagus nerve is involved in the development of compensatory kidney hypertrophy. PMID:3825553

  10. Temporary inhibition of growth and adrenal suppression associated with the use of steroid nose drops

    Microsoft Academic Search

    C. E. Daman Willems; R. Dinwiddie; D. B. Grant; R. P A. Rivers; M. Zahir

    1994-01-01

    Inhibition of growth and adrenal suppression are reported following the use of intranasal betamethasone (0.1%) in a 9-year-old boy with cystic fibrosis and nasal polyps and in a 3-year-old girl with allergic rhinitis. On stopping treatment catch-up growth occurred and adrenal function returned to normal.

  11. Inhibition of phenolic acid metabolism results in precocious cell death and altered cell morphology in leaves of transgenic tobacco plants

    PubMed Central

    Tamagnone, L; Merida, A; Stacey, N; Plaskitt, K; Parr, A; Chang, CF; Lynn, D; Dow, JM; Roberts, K; Martin, C

    1998-01-01

    Several complex phenotypic changes are induced when the transcription factor AmMYB308 is overexpressed in transgenic tobacco plants. We have previously shown that the primary effect of this transcription factor is to inhibit phenolic acid metabolism. In the plants that we produced, two morphological features were prominent: abnormal leaf palisade development and induction of premature cell death in mature leaves. Evidence from the analysis of these transgenic plants suggests that both changes resulted from the lack of phenolic intermediates. These results emphasize the importance of phenolic secondary metabolites in the normal growth and development of tobacco. We suggest that phenolic acid derivatives are important signaling molecules in the final stages of leaf palisade formation and that phenolic acid derivatives also play a prominent role in tissue senescence. PMID:9811790

  12. Lactobacillus-mediated inhibition of clinical toxic shock syndrome Staphylococcus aureus strains and its relation to acid and peroxide production.

    PubMed

    Elkins, Christopher A; Muñoz, María Enriqueta; Mullis, Lisa B; Stingley, Robin L; Hart, Mark E

    2008-11-01

    The inhibitory activities of 39 strains representing 20 different species of Lactobacillus toward a menstrual toxic shock syndrome (TSS) Staphylococcus aureus archetype strain MN8 were investigated. Nearly every strain (38 of 39) produced an inhibitory effect under both aerobic and anaerobic conditions when assayed on agar medium. In addition, the MN8 inhibition was conserved against at least 10 other clinical TSS S. aureus isolates and, interestingly, required actively growing cultures of Lactobacillus (verified with a two-well co-culture system in broth medium). This general uniform inhibition could be ameliorated by organic buffer (PIPES) supplied in the growth medium and, with only one exception, MRS medium adjusted with non-organic acid (HCl) failed to support growth of TSS strains at or below pH 5.5. By comparison, the vast majority of lactobacilli in this study decreased culture pH to a range of 4-5. Hydrogen peroxide production by the lactobacilli was also assessed and verified by two different methodologies revealing a broad spectrum of phenotypes that, contrary to reports touting its effectiveness, did not seem to correspond with our inhibition studies. Furthermore, resistances to peroxide by MN8, other TSS strains, and a subset of lactobacilli used in this study were nearly identical whereas the S. aureus collection was slightly more sensitive to racemic lactic acid than the lactobacilli. Collectively, these data suggest that the underlying inhibition toward Staphylococcus is generally conserved in Lactobacillus sp. and is related to a common factor in this genus involving promotion of acidic conditions. PMID:18926917

  13. Inhibiting Kirkendall void growth in welded bimetallic structures

    NASA Technical Reports Server (NTRS)

    Arcella, F. G.; Lessmann, G. A.; Lindberg, R. A.

    1975-01-01

    Technique employs pre-aged, void-free junction composed of parent materials. Basic process for Kirkendall void inhibition can be applied to thermionic power systems, high temperature seals, high temperature junctions between any two metals of differing melting points where Kirkendall void formation would be detrimental.

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

    NASA Technical Reports Server (NTRS)

    Moore, R.; Dickey, K.

    1985-01-01

    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.

  15. Cytokine-induced inhibition of Plasmodium falciparum erythrocytic growth in vitro.

    PubMed Central

    Orago, A S; Facer, C A

    1993-01-01

    The addition of recombinant cytokines to Plasmodium falciparum in vitro cultures retarded the growth of the parasite with the effect of recombinant IL-2 (rIL-2) > interferon-gamma (IFN-gamma) > tumour necrosis factor-beta (TNF-beta). The process was concentration dependent, being greatest at 30,000 U/ml and required a 72-h period of continuous exposure for maximum effect. Growth inhibition, as determined morphologically and radiometrically, was a consequence of defective schizont maturation rather than inhibition of merozoite invasion. It was cumulative and detectable within one erythrocytic (48 h) growth cycle. Images Fig. 2 PMID:8428394

  16. SPARC Inhibits Epithelial Cell Proliferation in Part through Stimulation of the Transforming Growth Factor-?–Signaling System

    PubMed Central

    Schiemann, Barbara J.; Neil, Jason R.; Schiemann, William P.

    2003-01-01

    Secreted protein, acidic and rich in cysteine (SPARC) is a multifunctional secreted protein that regulates cell–cell and cell–matrix interactions, leading to alterations in cell adhesion, motility, and proliferation. Although SPARC is expressed in epithelial cells, its ability to regulate epithelial cell growth remains largely unknown. We show herein that SPARC strongly inhibited DNA synthesis in transforming growth factor (TGF)-?–sensitive Mv1Lu cells, whereas moderately inhibiting that in TGF-?–insensitive Mv1Lu cells (i.e., R1B cells). Overexpression of dominant-negative Smad3 in Mv1Lu cells, which abrogated growth arrest by TGF-?, also attenuated growth arrest stimulated by SPARC. Moreover, the extracellular calcium-binding domain of SPARC (i.e., SPARC-EC) was sufficient to inhibit Mv1Lu cell proliferation but not that of R1B cells. Similar to TGF-? and thrombospondin-1, treatment of Mv1Lu cells with SPARC or SPARC-EC stimulated Smad2 phosphorylation and Smad2/3 nuclear translocation: the latter response to all agonists was abrogated in R1B cells or by pretreatment of Mv1Lu cells with neutralizing TGF-? antibodies. SPARC also stimulated Smad2 phosphorylation in MB114 endothelial cells but had no effect on bone morphogenetic protein-regulated Smad1 phosphorylation in either Mv1Lu or MB114 cells. Finally, SPARC and SPARC-EC stimulated TGF-?–responsive reporter gene expression through a TGF-? receptor- and Smad2/3-dependent pathway in Mv1Lu cells. Collectively, our findings identify a novel mechanism whereby SPARC inhibits epithelial cell proliferation by selectively commandeering the TGF-? signaling system, doing so through coupling of SPARC-EC to a TGF-? receptor- and Smad2/3-dependent pathway. PMID:14517312

  17. 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...

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

    E-print Network

    Hammock, Bruce D.

    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

  19. [Kinetic aspects of inhibition of the phytopathogenic fungi growth by rhizospera bacteria].

    PubMed

    Minaeva, O M; Akimova, E E; Evdokimov, E V

    2008-01-01

    Kinetics of growth inhibition of fungi Fusarium and Bipolaris caused by bacteria Pseudomonas sp. V-6798 and Azotobacter chroococum V-2272 D on dense nutrient media, both in single-crop system and by coinoculation, was demonstrated. The speed of fungal colonies growth as a function of bacteria concentration in inoculate was shown to be in accordance with the Ierysalimskii modified equation. The degree of antagonistic activity was suggested to be assessed by the constant of inhibition (Ki) and residual rate of fungi growth. Constant of inhibition of fungal growth by bacteria varied within 10-100 cells/ml for observed species. More effective fungistatic influence of bacterial strains in combined culture was observed. Parameters reported in the present study allow comparing the degree of bacteria antifungal activity in vitro. Suggested screening method could be used for selection of bacteria as activity biofungicide and while selecting biomedication for defined plant pathogen disruption. PMID:18822777

  20. Dietary agonists of TRPV1 inhibit gastric acid secretion in mice.

    PubMed

    Okumi, Hirokuni; Tashima, Kimihito; Matsumoto, Kenjiro; Namiki, Takao; Terasawa, Katsutoshi; Horie, Syunji

    2012-11-01

    Capsaicin and 6-gingerol, pungent components of chilli pepper and ginger, are known as dietary agonists of transient receptor potential vanilloid-1. Transient receptor potential vanilloid-1 nerve fibers are recognized to play a role in gastric mucosal integrity in rats. In the present studies, we examined the acute effects of peroral administration of capsaicin and 6-gingerol on gastric acid secretion in conscious mice. These agents were given p.?o. 30?min before the pylorus was ligated. Oral administration of capsaicin (1.0-100?mg/kg) or 6-gingerol (1.5-50?mg/kg) significantly and dose-dependently inhibited basal acid secretion. Pretreatment with BCTC, a transient receptor potential vanilloid-1 antagonist, significantly reversed the reduced basal acid secretion by capsaicin or 6-gingerol. The combination of the lowest doses of capsaicin and 6-gingerol markedly inhibited basal acid secretion in conscious mice and this was also significantly reversed by BCTC. Moreover, the combination of the maximal dose of capsaicin and 6-gingerol inhibited basal acid secretion only to the level of a single administration of the maximal dose of capsaicin. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on the inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1. In separate experiments, intraduodenal administration of either capsaicin (30?mg/kg) or 6-gingerol (15?mg/kg), whose doses were observed to have a significant inhibitory effect by oral administration, tended to inhibit basal acid secretion compared with the vehicle. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1, and oral administration of transient receptor potential vanilloid-1 agonists directly stimulates transient receptor potential vanilloid-1 in the gastric lumen, resulting in a potent reduction of gastric acid secretion. PMID:23047250

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

    PubMed

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

    2015-03-15

    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

  2. Inhibition of human breast carcinoma proliferation, migration, chemoinvasion and solid tumour growth by DNAzymes targeting the zinc finger transcription factor EGR-1

    PubMed Central

    Mitchell, Ainslie; Dass, Crispin R.; Sun, Lun-Quan; Khachigian, Levon M.

    2004-01-01

    DNAzymes (synthetic catalytic DNA) have emerged as a new class of nucleic acid-based gene silencing agent. Using DNAzymes targeting the human mRNA of the immediate-early gene and C2H2-class zinc finger transcription factor early growth response-1 (EGR-1), we demonstrate here that EGR-1 plays an indispensable role in breast cancer proliferation, migration, chemoinvasion and xenograft growth in nude mice. DNAzyme inhibition of these tumorigenic processes and EGR-1 protein expression in breast carcinoma cells is sequence-specific and EGR-1 transcription-independent. These agents inhibit breast carcinoma cell migration and chemoinvasion in microchemotaxis chambers and solid tumour growth in athymic nude mice. Thus, DNAzymes targeting specific genes can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as useful anti-cancer agents. PMID:15181171

  3. Docosahexaenoic acid selectively inhibits plasma membrane targeting of lipidated proteins

    Microsoft Academic Search

    Jeongmin Seo; Rola Barhoumi; Arthur E. Johnson; Joanne R. Lupton; Robert S. Chapkin

    2006-01-01

    Membrane localization of lipidated cytosolic signaling proteins is mediated by interactions between specific lipid anchors and membranes, but little is known about the regulatory role of membrane composition in lipidated protein membrane targeting. Here, using green fluorescent protein (GFP) chimeras and quantitative fluorescence microscopy in living mouse colonocytes, we show that docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid (PUFA)

  4. Ethanol-induced inhibition of chick brain growth.

    PubMed

    Boyd, J W; Kalmus, G W; Pennington, S N

    1984-01-01

    Retarded fetal brain growth is associated with a high incidence of mental retardation among the offspring of chronic alcoholic mothers. Research using an embryonic chick model suggests that ethanol exposure suppresses fetal development including suppression of brain growth. Total brain cyclic AMP content and endogenous brain protein kinase specific activity are not altered by ethanol; however, ethanol exposure does significantly stimulate kinase catalytic activity measured in the presence of saturating amounts of exogenous cyclic AMP. PMID:6091489

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

    Microsoft Academic Search

    Zahida Iqbal; Syuntaro Hiradate; Hiroshi Araya; Yoshiharu Fujii

    2004-01-01

    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

  6. Inhibition of gastric H(+),K(+)-ATPase and Helicobacter pylori growth by phenolic antioxidants of Curcuma amada.

    PubMed

    Siddaraju, M N; Dharmesh, Shylaja M

    2007-09-01

    Gastric ulcer is the most prevalent gastrointestinal disorder, resulting from oxidative stress, Helicobacter pylori infection, up-regulation of proton potassium ATPase (PPA) activity, down-regulation of gastric mucosal defense, etc. In this paper it is reported that phenolic fractions of Curcuma amada, commonly known as mango ginger, acted as potent inhibitors of PPA and H. pylori growth. Mango ginger free phenolics (MGFP) and mango ginger bound phenolics (MGBP) inhibited PPA at IC50 values of 2.2 +/- 0.21 and 0.7 +/- 0.08 microg/mL, respectively, exhibiting 9-27-fold better potency over lansoprazole (IC(50) of 19.3 +/- 2.2 microg/mL). MGFP is constituted by caffeic (26%), gentisic (24%), ferulic (20%), gallic (10%), cinnamic (7%), and protocatechuic acids (7%) and MGBP by ferulic (47%), cinnamic (29%), p-coumaric acid (11%), and syringic (5%) acids as major phenolic acids. MGFP and MGBP further exhibited free radical scavenging (IC(50) of 2.2 +/- 0.17 and 4.2 +/- 0.36 microg/mL), reducing power abilities (193-104 units/g), inhibition of lipid peroxidation (IC(50) of 10.3 +/- 0.91 and 15.6 +/- 1.6 microg/mL), and DNA protection (80% at 4 microg), indicating strong antioxidative properties. MGFP and MGBP thus may be potential and inexpensive multistep blockers against ulcers. PMID:17725316

  7. Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative.

    PubMed

    Ghizzoni, Massimo; Boltjes, André; Graaf, Chris de; Haisma, Hidde J; Dekker, Frank J

    2010-08-15

    Several lines of evidence indicate that histone acetyltransferases (HATs) are novel drug targets for treatment of diseases like, for example, cancer and inflammation. The natural product anacardic acid is a starting point for development of small molecule inhibitors of the histone acetyltransferase (HAT) p300/CBP associated factor (PCAF). In order to optimize the inhibitory potency, a binding model for PCAF inhibition by anacardic acid was proposed and new anacardic acid derivatives were designed. Ten new derivatives were synthesized using a novel synthetic route. One compound showed a twofold improved inhibitory potency for the PCAF HAT activity and a twofold improved inhibition of histone acetylation in HEP G2 cells. PMID:20655754

  8. Effects of humic acids on the growth of bacteria

    Microsoft Academic Search

    V. V. Tikhonov; A. V. Yakushev; Yu. A. Zavgorodnyaya; B. A. Byzov; V. V. Demin

    2010-01-01

    The influence of humic acids of different origins on the growth of bacterial cultures of different taxa isolated from the\\u000a soil and the digestive tracts of earthworms (Aporrectodea caliginosa)—habitats with contrasting conditions—was studied. More than half of the soil and intestinal isolates from the 170 tested\\u000a strains grew on the humic acid of brown coal as the only carbon source.

  9. Evidence against the acid-growth theory of auxin action

    Microsoft Academic Search

    U. Kutschera; P. Schopfer

    1985-01-01

    Four experimental predictions of the ‘acid-growth theory’ of auxin (indole-3-acetic acid, IAA) action in inducing cell elongation were reinvestigated using abraded segments of maize (Zea mays L.) coleoptiles. i) Quantitative comparison of segment elongation and medium-acidification kinetics measured in the same sample of tissue reveals that these IAA-induced processes are neither correlated in time nor responding coordinately to cations present

  10. Growth inhibition of experimental pancreatic cancers and sustained reduction in epidermal growth factor receptors during therapy with hormonal peptide analogs

    Microsoft Academic Search

    Karoly Szepesházi; Gabor Halmos; Andrew V. Schally; José M. Arencibia; Kate Groot; Manuel Vadillo-Buenfil; Eulalia Rodriguez-Martin

    1999-01-01

    Reduction in receptors for epidermal growth factor (EGF) in cancers appears to be one of the principal mechanisms through\\u000a which peptide hormone analogs can inhibit tumor growth. In this study, hamsters with nitrosamine-induced pancreatic cancers\\u000a were treated for 8 weeks with bombesin\\/gastrin-releasing peptide (GRP) antagonist RC-3095, somatostatin analog RC-160 or the\\u000a luteinizing hormone-releasing hormone antagonist Cetrorelix, using sustained delivery systems

  11. Transforming Growth Factor-b-induced Growth Inhibition in a Smad4 Mutant Colon Adenoma Cell Line1

    Microsoft Academic Search

    Stephen P. Fink; Sandra E. Swinler; James D. Lutterbaugh; Joan Massague; Sam Thiagalingam; Kenneth W. Kinzler; Bert Vogelstein; James K. V. Willson; Sanford Markowitz

    Transforming growth factor-b (TGF-b) inhibits growth and induces apoptosis of colon epithelial cells. Binding of TGF-b to its receptor induces phosphorylation of the Smad proteins Smad2 and Smad3, which then form heteromeric complexes with Smad4, translocate to the nucleus, and activate gene transcription. Smad4 function has been considered an obli- gate requirement for TGF-b signaling, and Smad4 mutations present in

  12. TGF beta-induced growth inhibition in primary fibroblasts requires the retinoblastoma protein.

    PubMed Central

    Herrera, R E; Mäkelä, T P; Weinberg, R A

    1996-01-01

    Transforming growth factor beta (TGF beta) inhibits cell proliferation by inducing a G1 cell-cycle arrest. Cyclin/CDK complexes have been implicated in this arrest, because TGF beta treatment leads to inhibition of cyclin/CDK activity. We have investigated the role of the retinoblastoma protein (pRb) in TGF beta-induced growth arrest by using RB+/+ and RB-/- primary mouse embryo fibroblasts. In both of these cell types, TGF beta inhibits CDK4-associated kinase activity. However, whereas CDK2-associated kinase activity was completely inhibited by TGF beta in the wild-type cells, it was reduced only slightly in the RB mutant cells. In addition, at high-cell density the growth-inhibitory effects of TGF beta are no longer observed in the RB-/- cells; on the contrary, TGF beta treatment promotes the growth of these mutant fibroblasts. Thus, under certain cellular growth conditions, elimination of pRb transforms the growth-inhibitory effects of TGF beta into growth-stimulatory effects. These observations could help to explain why TGF beta is often found to enhance tumorigenicity in vivo and why inactivation of the RB gene leads to tumorigenesis. Images PMID:8885230

  13. BRD4 Inhibitor Inhibits Colorectal Cancer Growth and Metastasis

    PubMed Central

    Hu, Yuan; Zhou, Jieqiong; Ye, Fei; Xiong, Huabao; Peng, Liang; Zheng, Zihan; Xu, Feihong; Cui, Miao; Wei, Chengguo; Wang, Xinying; Wang, Zhongqiu; Zhu, Hongfa; Lee, Peng; Zhou, Mingming; Jiang, Bo; Zhang, David Y.

    2015-01-01

    Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal. PMID:25603177

  14. Ivermectin Inhibits Growth of Chlamydia trachomatis in Epithelial Cells

    PubMed Central

    Pettengill, Matthew A.; Lam, Verissa W.; Ollawa, Ikechukwu; Marques-da-Silva, Camila; Ojcius, David M.

    2012-01-01

    Ivermectin is currently approved for treatment of both clinical and veterinary infections by nematodes, including Onchocerca cervicalis in horses and Onchocerca volvulus in humans. However, ivermectin has never been shown to be effective against bacterial pathogens. Here we show that ivermectin also inhibits infection of epithelial cells by the bacterial pathogen, Chlamydia trachomatis, at doses that could be envisioned clinically for sexually-transmitted or ocular infections by Chlamydia. PMID:23119027

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

    PubMed Central

    2014-01-01

    Background Drug resistance is a cause of ovarian cancer recurrence and low overall survival rates. There is a need for more effective treatment approaches because the development of new drug is expensive and time consuming. Alternatively, the concept of ‘drug repurposing’ is promising. We focused on Bithionol (BT), a clinically approved anti-parasitic drug as an anti-ovarian cancer drug. BT has previously been shown to inhibit solid tumor growth in several preclinical cancer models. A better understanding of the anti-tumor effects and mechanism(s) of action of BT in ovarian cancer cells is essential for further exploring its therapeutic potential against ovarian cancer. Methods The cytotoxic effects of BT against a panel of ovarian cancer cell lines were determined by Presto Blue cell viability assay. Markers of apoptosis such as caspases 3/7, cPARP induction, nuclear condensation and mitochondrial transmembrane depolarization were assessed using microscopic, FACS and immunoblotting methods. Mechanism(s) of action of BT such as cell cycle arrest, reactive oxygen species (ROS) generation, autotaxin (ATX) inhibition and effects on MAPK and NF-kB signalling were determined by FACS analysis, immunoblotting and colorimetric methods. Results BT caused dose dependent cytotoxicity against all ovarian cancer cell lines tested with IC50 values ranging from 19 ?M – 60 ?M. Cisplatin-resistant variants of A2780 and IGROV-1 have shown almost similar IC50 values compared to their sensitive counterparts. Apoptotic cell death was shown by expression of caspases 3/7, cPARP, loss of mitochondrial potential, nuclear condensation, and up-regulation of p38 and reduced expression of pAkt, pNF-?B, pI?B?, XIAP, bcl-2 and bcl-xl. BT treatment resulted in cell cycle arrest at G1/M phase and increased ROS generation. Treatment with ascorbic acid resulted in partial restoration of cell viability. In addition, dose and time dependent inhibition of ATX was observed. Conclusions BT exhibits cytotoxic effects on various ovarian cancer cell lines regardless of their sensitivities to cisplatin. Cell death appears to be via caspases mediated apoptosis. The mechanisms of action appear to be partly via cell cycle arrest, ROS generation and inhibition of ATX. The present study provides preclinical data suggesting a potential therapeutic role for BT against recurrent ovarian cancer. PMID:24495391

  16. Non-competitive product inhibition in lactic acid fermentation from glucose

    Microsoft Academic Search

    Hitomi Ohara; Keiichiro Hiyama; Toshiomi Yoshida

    1992-01-01

    A kinetic study regarding product inhibition in lactic acid fermentation by Streptococcus faecalis, which produces l-lactic acid, was performed in a chemostat at various feed concentrations of glucose (10, 20, and 30 g\\/l) at pH 7.0. Steady-state kinetic constants for the specific consumption rate of glucose and the specific production rate of lactic acid were determined at a residual glucose

  17. Inhibition of cell-free protein synthesis by analogues of aurintricarboxylic acid.

    PubMed

    Kreamer, B L; Anderson, J; Liu, D S; Sparks, M B; Richardson, A

    1978-12-01

    Aurintricarboxylic acid is a potent inhibitor of cell-free protein synthesis by the post-mitochondrial supernatant of chick brain and the translation of mRNA by wheat germ lysate. Comparison of commercially available and chemically synthesized analogues of aurintricarboxylic acid indicates that the unique aurin triphenyl methane ring system and the carboxylic acid groups are both necessary for inhibition of cell-free protein synthesis in both systems. PMID:750075

  18. Inhibition of breast cancer growth and metastasis by a biomimetic peptide

    PubMed Central

    Lee, Esak; Lee, Seung Jae; Koskimaki, Jacob E.; Han, Zheyi; Pandey, Niranjan B.; Popel, Aleksander S.

    2014-01-01

    Metastasis is the main cause of mortality in cancer patients. Though there are many anti-cancer drugs targeting primary tumor growth, anti-metastatic agents are rarely developed. Angiogenesis and lymphangiogenesis are crucial for cancer progression, particularly, lymphangiogenesis is pivotal for metastasis in breast cancer. Here we report that a novel collagen IV derived biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis. The peptide inhibits blood and lymphatic endothelial cell viability, migration, adhesion, and tube formation by targeting IGF1R and Met signals. The peptide blocks MDA-MB-231 tumor growth by inhibiting tumor angiogenesis in vivo. Moreover, the peptide inhibits lymphangiogenesis in primary tumors. MDA-MB-231 tumor conditioned media (TCM) was employed to accelerate spontaneous metastasis in tumor xenografts, and the anti-metastatic activity of the peptide was tested in this model. The peptide prevents metastasis to the lungs and lymph nodes by inhibiting TCM-induced lymphangiogenesis and angiogenesis in the pre-metastatic organs. In summary, a novel biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis in the pre-metastatic organs as well as primary tumors. PMID:25409905

  19. Lactobacillus fermentum isolated from human colonic mucosal biopsy inhibits the growth and adhesion of enteric and foodborne pathogens.

    PubMed

    Varma, Parvathi; Dinesh, Kavitha R; Menon, Krishna K; Biswas, Raja

    2010-01-01

    A number of Lactobacillus species are used as probiotic strains in order to benefit health. We have isolated L. fermentum from human colonic mucosal biopsy samples that possess antimicrobial activities against entroinvasive and foodborne pathogens such as Escherichia coli, Salmonella paratyphi A, Shigella sonnei, Staphylococcus aureus, Enterococcus faecalis, Proteus mirabilis, Pseudomonas aeruginosa, and Vibrio sp. In addition to lactic acid, L. fermentum secretes antimicrobial proteinacious compound(s) that was found to be active even at neutral pH (pH 7.0). The compound was sensitive to heat treatment and trypsin digestion. Lactobacillus fermentum inhibited the adhesion of enteropathogens to intestinal epithelial cells in vitro. Isolated cell surface associated proteins (SAPs) from L. fermentum were sufficient for the adhesion exclusions of enteropathogenic E. coli. Our results indicate that L. fermentum produces antimicrobial compounds and SAPs to inhibit the growth and adhesion of enteropathogens, respectively. PMID:21535608

  20. Dual effect of metformin on growth inhibition and oestradiol production in breast cancer cells.

    PubMed

    Rice, S; Pellat, L; Ahmetaga, A; Bano, G; Mason, H D; Whitehead, S A

    2015-04-01

    Evidence has been accumulating for a role for metformin in reducing breast cancer risk in post-menopausal women. It inhibits growth of breast cancer cells via several mechanisms, primarily the AMPK/mTOR signalling pathway. Another possible protective mechanism may be the ability of metformin to inhibit aromatase activity. In the present study, we investigated the effects of metformin on the basal growth of MCF-7 cells, after oestradiol (E2) stimulation and after the inhibition of mTOR by rapamycin. Secondly, we investigated the effects of metformin on the activity of a number of steroidogenic enzymes and the mRNA expression of aromatase and steroid sulphatase (STS). High doses of metformin significantly inhibited both basal and oestrogen?stimulated cell division. Low-dose rapamycin (10-10 M) did not inhibit growth, but the addition of metformin induced a significant reduction in growth. High-dose rapamycin (10-8 M) inhibited growth, and this was further attenuated by the addition of metformin. Exposure to low (10-7 M) and high (10-4 M) doses of metformin for 7-10 days significantly reduced the conversion of androstenedione (ANDRO) and testosterone (TESTO) (both requiring aromatase), but not the conversion of oestrone or oestrone sulphate (ES) via 17?-hydroxysteroid dehydrogenase/sulphatase to E2. This attenuation was via a downregulation in the expression of total aromatase mRNA and promoter II, whilst the expression of sulphatase was unaffected by metformin. In conclusion, plasma levels of metformin have a dual therapeutic action, first by directly inhibiting cell proliferation which can be augmented by rapamycin analogues, and secondly, by inhibiting aromatase activity and reducing the local conversion of androgens to E2. PMID:25716282

  1. Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide

    NASA Technical Reports Server (NTRS)

    Betz, N. A.; Westhoff, B. A.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Our laboratory has purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) from intact bovine cerebral cortex cells. Evidence presented here demonstrates that sensitivity to CeReS-18-induced growth inhibition in BALB-c 3T3 cells is influenced by calcium, such that a decrease in the calcium concentration in the growth medium results in an increase in sensitivity to CeReS-18. Calcium did not alter CeReS-18 binding to its cell surface receptor and CeReS-18 does not bind calcium directly. Addition of calcium, but not magnesium, to CeReS-18-inhibited 3T3 cells results in reentry into the cell cycle. A greater than 3-hour exposure to increased calcium is required for escape from CeReS-18-induced growth inhibition. The calcium ionophore ionomycin could partially mimic the effect of increasing extracellular calcium, but thapsigargin was ineffective in inducing escape from growth inhibition. Increasing extracellular calcium 10-fold resulted in an approximately 7-fold increase in total cell-associated 45Ca+2, while free intracellular calcium only increased approximately 30%. However, addition of CeReS-18 did not affect total cell-associated calcium or the increase in total cell-associated calcium observed with an increase in extracellular calcium. Serum addition induced mobilization of intracellular calcium and influx across the plasma membrane in 3T3 cells, and pretreatment of 3T3 cells with CeReS-18 appeared to inhibit these calcium mobilization events. These results suggest that a calcium-sensitive step exists in the recovery from CeReS-18-induced growth inhibition. CeReS-18 may inhibit cell proliferation through a novel mechanism involving altering the intracellular calcium mobilization/regulation necessary for cell cycle progression.

  2. Main and interaction effects of acetic acid, furfural, and p-hydroxybenzoic acid on growth and ethanol productivity of yeasts

    SciTech Connect

    Palmqvist, E.; Grage, H.; Meinander, N.Q.; Hahn-Haegerdal, B. [Univ. of Lund (Sweden)

    1999-04-05

    The influence of the factors acetic acid, furfural, and p-hydroxybenzoic acid on the ethanol yield (Y{sub EtOH}) of Saccharomyces cerevisiae, bakers` yeast, S. cerevisiae ATCC 96581, and Candida shehatae NJ 23 was investigated using a 2{sup 3}-full factorial design with 3 centerpoints. The results indicated that acetic acid inhibited the fermentation by C. shehatae NJ 23 markedly more than by bakers` yeast, whereas no significant difference in tolerance towards the compounds was detected between the S. cerevisiae strains. Furfural and the lignin derived compound p-hydroxybenzoic acid did not affect any of the yeasts at the cell mass concentration used. The results indicated that the linear model was not adequate to describe the experimental data. Based on the results from the 2{sup 3}-full factorial experiment, an extended experiment was designed based on a central composite design to investigate the influence of the factors on the specific growth rate ({mu}), biomass yield (Y{sub x}), volumetric ethanol productivity (Q{sub EtOH}), and Y{sub EtOH}. Bakers` yeast was chosen in the extended experiment due to its better tolerance towards acetic acid, which makes it a more interesting organism for use in industrial fermentations of lignocellulosic hydrolysates.

  3. Bisphenol A inhibits cultured mouse ovarian follicle growth partially via the aryl hydrocarbon receptor signaling pathway

    PubMed Central

    Ziv-Gal, Ayelet; Craig, Zelieann R.; Wang, Wei; Flaws, Jodi A.

    2013-01-01

    Bisphenol A (BPA) is an endocrine disruptor that inhibits growth of mouse ovarian follicles and disrupts steroidogenesis at a dose of 438 ?M. However, the effects of lower doses of BPA and its mechanism of action in ovarian follicles are unknown. We hypothesized that low doses of BPA inhibit follicular growth and decrease estradiol levels through the aryl hydrocarbon receptor (AHR) pathway. Antral follicles from wild-type and Ahr knock-out (AhrKO) mice were cultured for 96 hours. Follicle diameters and estradiol levels then were compared in wild-type and AhrKO follicles ± BPA (0.004 - 438 ?M). BPA inhibited follicle growth (110 - 438 ?M) and decreased estradiol levels (43.8 - 438 ?M) in wild-type and AhrKO follicles. However, at BPA 110 ?M, inhibition of growth in AhrKO follicles was attenuated compared to wild-type follicles. These data suggest that BPA may inhibit follicle growth partially via the AHR pathway, whereas its effects on estradiol synthesis likely involve other mechanisms. PMID:23928317

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

    PubMed Central

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

    2014-01-01

    Purpose Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid (ZOL) represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, ZOL triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), which could enhance tumor cell survival and treatment resistance. We hypothesized that targeting CLU using siRNA or the antisense drug, OGX-011, will suppress treatment-induced CLU induction and enhance ZOL-induced cell death in osteosarcoma (OS) cells. Methods The combined effects of OGX-011 and ZOL were investigated in vitro on cell growth, viability, apoptosis and cell cycle repartition of ZOL-sensitive or -resistant human OS cell lines (SaOS2, U2OS, MG63 and MNNG/HOS). Results In OS cell lines, ZOL increased levels of HSPs, especially CLU, in a dose- and time-dependent manner by mechanism including increased HSF1 transcription activity. The OS resistant cells to ZOL exhibited higher CLU expression level than the sensitive cells. Moreover, CLU overexpression protects OS sensitive cells to ZOL-induced cell death by modulating the MDR1 and farnesyl diphosphate synthase expression. OGX-011 suppressed treatment-induced increases in CLU and synergistically enhanced the activity of ZOL on cell growth and apoptosis. These biologic events were accompanied by decreased expression of HSPs, MDR1 and HSF1 transcriptional activity. In vivo, OGX-011, administered 3 times a week (IP, 20mg/kg), potentiated the effect of ZOL (s.c; 50?g/kg), significantly inhibiting tumor growth by 50% and prolonging survival in MNNG/HOS xenograft model compared to ZOL alone. Conclusion These results indicate that ZOL-mediated induction of CLU can be attenuated by OGX-011, with synergistic effects on delaying progression of osteosarcoma. PMID:25138053

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

    Microsoft Academic Search

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

    2007-01-01

    The corrosion inhibition of mild steel in sulfuric acid by methionine (MTI) was investigated using electrochemical techniques. The effect of KI additives on corrosion inhibition efficiency was also studied. The results reveal that MTI inhibited the corrosion reaction by adsorption onto the metal\\/solution interface. Inhibition efficiency increased with MTI concentration and synergistically increased in the presence of KI, with an

  6. Effects of humic acids on the growth of bacteria

    NASA Astrophysics Data System (ADS)

    Tikhonov, V. V.; Yakushev, A. V.; Zavgorodnyaya, Yu. A.; Byzov, B. A.; Demin, V. V.

    2010-03-01

    The influence of humic acids of different origins on the growth of bacterial cultures of different taxa isolated from the soil and the digestive tracts of earthworms ( Aporrectodea caliginosa)—habitats with contrasting conditions—was studied. More than half of the soil and intestinal isolates from the 170 tested strains grew on the humic acid of brown coal as the only carbon source. The specific growth rate of the bacteria isolated from the intestines of the earthworms was higher than that of the soil bacteria. The use of humic acids by intestinal bacteria confirms the possibility of symbiotic digestion by earthworms with the participation of bacterial symbionts. Humic acids at a concentration of 0.1 g/l stimulated the growth of the soil and intestinal bacteria strains (66 strains out of 161) on Czapek’s medium with glucose (1 g/l), probably, acting as a regulator of the cell metabolism. On the medium with the humic acid, the intestinal bacteria grew faster than the soil isolates did. The most active growth of the intestinal isolates was observed by Paenibacillus sp., Pseudomonas putida, Delftia acidovorans, Microbacterium terregens, and Aeromonas sp.; among the soil ones were the representatives of the Pseudomonas genus. A response of the bacteria to the influence of humic acids was shown at the strain level using the example of Pseudomonas representatives. The Flexom humin preparation stimulated the growth of the hydrocarbon-oxidizing Acinetobacter sp. bacteria. This effect can be used for creating a new compound with the elevated activity of bacteria that are destroyers of oil and oil products.

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

    PubMed

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

    2011-06-01

    A plant extract from the fruits of saw palmetto, which is currently used to treat the androgen-dependent benign prostatic hyperplasia and PCa, served as source for new structure variants. We investigated the antiandrogenic potential of an ethanolic total extract and one of its main aromatic components anthranilic acid. An androgen receptor-antagonistic (antiandrogenic) effect of the extract was evident, and although anthranilic acid itself revealed no remarkable effect, its methyl ester, methyl anthranilate, exhibited antiandrogenic potential. Based on this chemical structure, we synthesized and investigated the antiandrogenic activity of four AnA ester derivatives, which were either novel or only little described in literature. These AnA esters inhibit the androgen-dependent transactivation of both the wild-type (wt) androgen receptor and the androgen receptor point mutant T877A, which often occurs in refractory PCa. Moreover, they inhibit the androgen receptor-induced expression of the endogenous prostate-specific antigen. Importantly, AnA esters repress the growth of human PCa cells. Deletion analyses of androgen receptor propose that the antiandrogenic effect of anthranilic acid esters is mediated by the ligand-binding domain, most likely through direct binding, without affecting androgen receptor protein levels. Taken together, the data suggest antiandrogenic potential of anthranilic acid ester derivatives, which can serve as lead structures for novel antiandrogens. PMID:21439024

  8. Inhibition of Glioblastoma Growth by the Thiadiazolidinone Compound TDZD-8

    Microsoft Academic Search

    Diana Aguilar-Morante; Jose Angel Morales-Garcia; Marina Sanz-Sancristobal; Miguel Angel Garcia-Cabezas; Angel Santos; Ana Perez-Castillo; Maciej Lesniak

    2010-01-01

    BackgroundThiadiazolidinones (TDZD) are small heterocyclic compounds first described as non-ATP competitive inhibitors of glycogen synthase kinase 3? (GSK-3?). In this study, we analyzed the effects of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), on murine GL261 cells growth in vitro and on the growth of established intracerebral murine gliomas in vivo.Methodology\\/Principal FindingsOur data show that TDZD-8 decreased proliferation and induced apoptosis of GL261 glioblastoma cells

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

    PubMed Central

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

    2010-01-01

    The multi-kinase inhibitor Sorafenib, is the first oral agent to show activity against human hepatocellular carcinoma (HCC). Apoptosis has been shown to be induced in HCC by several agents, including Sorafenib, as well as by the naturally occurring K vitamins (VKs). Since few non toxic agents have activity against HCC growth, we evaluated the activity of Sorafenib and K vitamins, both independently and together on the growth in vitro and in vivo of HCC cells. We found that when VK was combined with Sorafenib, the concentration of Sorafenib required for growth inhibition was substantially reduced. Conversely, VK enhanced Sorafenib effects in several HCC cell lines on growth inhibition. Growth could be inhibited at doses of VK plus Sorafenib that were ineffective with either agent alone,using vitamins K1, K2 and K5. Combination VK1 plus Sorafenib induced apoptosis on FACS, TUNEL staining and caspase activation. Phospho-ERK levels were decreased, as was Mcl-1, an ERK target. Sorafenib alone inhibited growth of transplantable HCC in vivo. At sub-effective Sorafenib doses in vivo, addition of VK1 caused major tumor regression, with decreased phospho-ERK and Mcl-1 staining. Thus, combination VK1 plus Sorafenib strongly induced growth inhibition and apoptosis in rodent and human HCC and inhibited the RAF/MEK/ERK pathway. VK1 alone activated PKA, a mediator of inhibitory Raf phosphorylation. Thus, each agent can antagonize Raf; Sorafenib as a direct inhibitor and VK1 through inhibitory Raf phosphorylation. Since both agents are available for human use, the combination has potential for improving Sorafenib effects in HCC. PMID:21351273

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2013-01-01

    This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA), on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231) with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis) with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer. PMID:24039831

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

    PubMed Central

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

    2013-01-01

    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

  13. Characterization of the Inhibition of K+ Absorption in Oat Roots by Salicylic Acid 1

    PubMed Central

    Harper, James R.; Balke, Nelson E.

    1981-01-01

    The phenolic compounds salicylic acid (o-hydroxybenzoic acid) and ferulic acid (4-hydroxy-3-methoxycinnamic acid) inhibited K+ (86Rb+) absorption in excised oat (Avena sativa L. cv. Goodfield) root tissue. Salicylic acid was the most inhibitory. The degree of inhibition was both concentration- and pH-dependent. With decreasing pH, the inhibitory effect of the phenolic increased. During the early stages of incubation, the time required to inhibit K+ absorption was also pH- and concentration-dependent. At pH 4.0, 5×10?4 molar salicylic acid inhibited K+ absorption about 60% within 1 minute; whereas, at pH 6.5, this concentration affected absorption only after 10 to 15 minutes. However, at 5 × 10?3 molar and pH 6.5, salicylic acid was inhibitory within 1 minute. The capacity of the tissue to recover following a 1-hour treatment in 5 × 10?4 molar salicylic acid ranged from no recovery at pH 4.5 to complete recovery at pH 7.5. The absorption of salicylic acid was pH-dependent, also. As pH decreased, more of the phenolic compound was absorbed by the tissue. The increased absorption of the compound at low pH most likely contributed to apparent tissue damage at pH 4.5 and might have accounted for the lack of recovery of K+ absorption as pH decreased. Under the proper conditions of pH and concentration, phenolic acids such as salicylic acid could significantly affect mineral absorption by plants in the field. PMID:16662106

  14. 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...

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

    PubMed

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

    2014-03-10

    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

  16. Inhibition of endogenous reverse transcriptase antagonizes human tumor growth

    Microsoft Academic Search

    Ilaria Sciamanna; Matteo Landriscina; Carmine Pittoggi; Michela Quirino; Cristina Mearelli; Rosanna Beraldi; Elisabetta Mattei; Annalucia Serafino; Alessandra Cassano; Paola Sinibaldi-Vallebona; Enrico Garaci; Carlo Barone; Corrado Spadafora

    2005-01-01

    Undifferentiated cells and embryos express high levels of endogenous non-telomerase reverse transcriptase (RT) of retroposon\\/retroviral origin. We previously found that RT inhibitors modulate cell growth and differentiation in several cell lines. We have now sought to establish whether high levels of RT activity are directly linked to cell transformation. To address this possibility, we have employed two different approaches to

  17. Pyruvate Inhibits Growth of Mammary Adenocarcinoma 13762 in Rats

    Microsoft Academic Search

    Ronald T. Stanko; Prakash Mulliek; Martha R. Clarke; Lydia C. Contis; Janine E. Janosky; Sai S. Ramasastry

    The growth of implanted mammary adenocarcinoma 13762 was mea- sured in rats consuming a liquid diet (35% fat, 18% protein, 47% carbo- hydrate) supplemented with pyruvate (37.3 g\\/liter; n = 13) or maltose- dextrin (placebo; n = 13) for 21 days. Mean tumor diameter, measured on day 11, 14, 18, and 21 subsequent to tumor implantation, was 41, 32, 21,

  18. Inhibition of dental plaque acid production by the salivary lactoperoxidase antimicrobial system.

    PubMed

    Tenovuo, J; Mansson-Rahemtulla, B; Pruitt, K M; Arnold, R

    1981-10-01

    Resting human whole saliva inhibited acid production by glucose-stimulated, homologous plaque. The degree of inhibition of plaque acid production correlated positively with the concentration of hypothiocyanite (OSCN-) ions in saliva. Supplementation of saliva with an appropriate combination of thiocyanate and hydrogen peroxide resulted in a significant increase in the concentration of OSCN- ions and in more effective inhibition of plaque acid production. In most cases, the inhibition was complete when the supplements were added directly to saliva-plaque mixtures. Acid production resumed when the inhibitory effect of OSCN- was reversed by addition of thiols. Among the oral defense factors, the salivary lactoperoxidase system seems to play an important role by producing highly reactive antibacterial products (including OSCN-) which can regulate bacterial metabolism in the human mouth. The concentration of OSCN- in normal human whole saliva seems to be just below the threshold level required for plaque inhibition. Therefore, enhancement of this system in vivo may be effective in the regulation of plaque acid production. PMID:7298182

  19. Inhibition of dental plaque acid production by the salivary lactoperoxidase antimicrobial system.

    PubMed Central

    Tenovuo, J; Mansson-Rahemtulla, B; Pruitt, K M; Arnold, R

    1981-01-01

    Resting human whole saliva inhibited acid production by glucose-stimulated, homologous plaque. The degree of inhibition of plaque acid production correlated positively with the concentration of hypothiocyanite (OSCN-) ions in saliva. Supplementation of saliva with an appropriate combination of thiocyanate and hydrogen peroxide resulted in a significant increase in the concentration of OSCN- ions and in more effective inhibition of plaque acid production. In most cases, the inhibition was complete when the supplements were added directly to saliva-plaque mixtures. Acid production resumed when the inhibitory effect of OSCN- was reversed by addition of thiols. Among the oral defense factors, the salivary lactoperoxidase system seems to play an important role by producing highly reactive antibacterial products (including OSCN-) which can regulate bacterial metabolism in the human mouth. The concentration of OSCN- in normal human whole saliva seems to be just below the threshold level required for plaque inhibition. Therefore, enhancement of this system in vivo may be effective in the regulation of plaque acid production. PMID:7298182

  20. Dual inhibition of arachidonic acid pathway by mulberry leaf extract.

    PubMed

    Chauhan, Seema; Devi, Uma; Kumar, Venkatesh R; Kumar, Vikas; Anwar, Firoz; Kaithwas, Gaurav

    2015-02-01

    The present work investigates the anti-inflammatory, analgesic and antipyretic activity of methanolic extract of mulberry leaves of variety S-1, S-13 and S-146. The S-146 extract was further evaluated for its efficacy against adjuvant arthritis in albino rats followed by inhibitory potential for COX 1, COX 2 and 5 LOX. The HPLC analysis enumerated the presence of morin, reversterol, scopoletin and 7-hydroxy coumarin as the major constituents. The anti-inflammatory, antipyretic and analgesic activity observed in the present experiment could be accredited to the dual inhibition in the AA pathway. The inhibition of COX and LOX enzymes could be imparted to the presence of resveraterol, morin, scopoletin and 7-hydroxy coumarin. PMID:25490949

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

    Microsoft Academic Search

    Fan Houbao; Li Chuanrong

    1999-01-01

    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

  2. GROWTH OF CAMPYLOBACTER ON MEDIA SUPPLEMENTED WITH ORGANIC ACIDS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Campylobacter spp. are the main cause of bacterial foodborne illnesses in humans, and contaminated poultry products are major sources of campylobacteriosis. In this study, the growth of Campylobacter spp. in media supplemented with organic acids was examined. Tryptose-yeast extract basal broth mediu...

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

    SciTech Connect

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

    2007-08-01

    High elastase and cathepsin G activities have been observed in chronic wounds. These levels can inhibit healing through degradation of growth factors, cytokines, and extracellular matrix proteins. Oleic acid (18:1) is a non-toxic elastase inhibitor with some potential for redressing the imbalance of elastase activity found in chronic wounds. Cotton wound dressing material was characterized as a transfer carrier for affinity uptake of 18:1 by albumin under conditions mimicking chronic wounds. 18:1-treated cotton was examined for its ability to bind and release the fatty acid in the presence of albumin. The mechanism of 18:1 uptake from cotton and binding by albumin was examined with both intact dressings and cotton fiber-designed chromatography. Raman spectra of the albumin-18:1 complexes under liquid-liquid equilibrium conditions revealed fully saturated albumin-18:1 complexes with a 1:1 weight ratio of albumin:18:1. Cotton chromatography under liquid-solid equilibrium conditions revealed oleic acid transfer from cotton to albumin at 27 mole equivalents of 18:1 per mole albumin. Cotton was contrasted with hydrogel, and hydrocolloid wound dressing for its comparative ability to lower elastase activity. Each dressing material evaluated was found to release 18:1 in the presence of albumin with significant inhibition of elastase activity. The 18:1-formulated wound dressings lowered elastase activity in a dose dependent manner in the order cotton gauze > hydrogel > hydrocolloid. In contrast the cationic serine protease Cathepsin G was inihibited by 18:1 within a narrow range of 18:1-cotton formulations. Four per cent Albumin solutions were most effective in binding cotton bound-18:1. However, 2% albumin was sufficient to transfer quantities of 18:1 necessary to achieve a significant elastase-lowering effect. Formulations with 128 mg 18:1/g cotton gauze had equivalent elastase lowering with 1 - 4% albumin. 18:1 bound to cotton wound dressings may have promise in the selective lowering of cationic serine protease activity useful in topical application for chronic inflammatory pathogenesis.

  4. Calystegines in Calystegia sepium do not inhibit fungal growth and invertase activity but interact with plant invertase.

    PubMed

    Höke, D; Dräger, B

    2004-01-01

    Calystegines are alkaloidal glycosidase inhibitors. They accumulate predominantly in young and meristemic parts of Calystegia sepium (Convolvulaceae). C. sepium, bindweed, infests meadows and cereal fields and is difficult to control chemically. Fungal pathogens against C. sepium are established as mycoherbicides. Stagonospora convolvuli LA39 attacks C. sepium and does not affect crop plants, but young plants of C. sepium are less susceptible to the fungus. The interaction of Stagonospora convolvuli with calystegines was investigated. Further, endophytic fungi of several classes were isolated from wild-grown Calystegia sepium leaves, and selected strains were tested for interaction with calystegines. Fungal growth on agar containing calystegines was not affected considerably. Plants in climate chambers were infected with an endophyte, Phomopsis, and with the fungal pathogen, Stagonospora convolvuli. Calystegine levels were measured in infected and non-infected plant tissues. Accumulation depended on developmental stage of the plant tissue and was not influenced by infection. Acid invertase was measured from fungal mycelia and from infected and non-infected plant tissues. Fungal acid invertase activity was not inhibited by 10 mM calystegine B (2), while invertase from C. sepium leaves was inhibited. It is concluded that calystegines do not inhibit fungal development and sucrose consumption under the conditions of the present investigation, but may act by redirection of plant carbohydrate metabolism. PMID:15045673

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

    PubMed Central

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

    2008-01-01

    Expression of fatty acid synthase (FASN), the key enzyme in de novo synthesis of long-chain fatty acids (FA), is normally low but increases in cancer. Consequently, FASN is a novel target for cancer therapy. However, because FASN inhibitors can lead to tumor stasis rather than shrinkage, non-invasive methods for assessing FASN inhibition are needed. To this end, we combined 1H, 31P and 13C magnetic resonance spectroscopy (MRS) (i) to monitor the metabolic consequences of FASN inhibition and (ii) to identify MRS-detectable metabolic biomarkers of response. Treatment of PC-3 cells with the FASN inhibitor Orlistat for up to 48 h resulted in inhibition of FASN activity by 70%, correlating with 74% inhibition of FA synthesis. Furthermore, we have determined that FASN inhibition results not only in lower phosphatidylcholine levels, but also in a 59% drop in the phospholipid precursor phosphocholine (PCho). This drop resulted from inhibition in PCho synthesis as a result of a reduction in the cellular activity of its synthetic enzyme choline kinase. The drop in PCho levels following FASN inhibition was confirmed in SKOV-3 ovarian cancer cells treated with Orlistat and in MCF-7 breast cancer cells treated with Orlistat as well as cerulenin. Combining data from all treated cells, the drop in PCho significantly correlated with the drop in de novo synthesized FA levels, identifying PCho as a potential non-invasive MRS-detectable biomarker of FASN inhibition in vivo. PMID:18723500

  6. Model for acid-base chemistry in nanoparticle growth (MABNAG)

    NASA Astrophysics Data System (ADS)

    Yli-Juuti, T.; Barsanti, K.; Hildebrandt Ruiz, L.; Kieloaho, A.-J.; Makkonen, U.; Petäjä, T.; Ruuskanen, T.; Kulmala, M.; Riipinen, I.

    2013-03-01

    Climatic effects of newly-formed atmospheric secondary aerosol particles are to a large extent determined by their condensational growth rates. However, all the vapors condensing on atmospheric nanoparticles and growing them to climatically relevant sizes are not identified yet and the effects of particle phase processes on particle growth rates are poorly known. Besides sulfuric acid, organic compounds are known to contribute significantly to atmospheric nanoparticle growth. In this study a particle growth model MABNAG (Model for Acid-Base chemistry in NAnoparticle Growth) was developed to study the effect of salt formation on nanoparticle growth, which has been proposed as a potential mechanism lowering the equilibrium vapor pressures of organic compounds through dissociation in the particle phase and thus preventing their evaporation. MABNAG is a model for monodisperse aqueous particles and it couples dynamics of condensation to particle phase chemistry. Non-zero equilibrium vapor pressures, with both size and composition dependence, are considered for condensation. The model was applied for atmospherically relevant systems with sulfuric acid, one organic acid, ammonia, one amine and water in the gas phase allowed to condense on 3-20 nm particles. The effect of dissociation of the organic acid was found to be small under ambient conditions typical for a boreal forest site, but considerable for base-rich environments (gas phase concentrations of about 1010 cm-3 for the sum of the bases). The contribution of the bases to particle mass decreased as particle size increased, except at very high gas phase concentrations of the bases. The relative importance of amine versus ammonia did not change significantly as a function of particle size. While our results give a reasonable first estimate on the maximum contribution of salt formation to nanoparticle growth, further studies on, e.g. the thermodynamic properties of the atmospheric organics, concentrations of low-volatility organic acids and amines, along with studies investigating the applicability of thermodynamics for the smallest nanoparticles are needed to truly understand the acid-base chemistry of atmospheric nanoparticles.

  7. Inhibition of the growth of Streptococcus mutans, Streptococcus sobrinus and Lactobacillus casei by oral peroxidase systems in human saliva.

    PubMed

    Lumikari, M; Soukka, T; Nurmio, S; Tenovuo, J

    1991-01-01

    Streptococcus mutans, Strep. sobrinus and Lactobacillus casei were grown in glucose-supplemented, sterilized, human whole saliva, adjusted to pH 5, 6 or 7. Components of the antibacterial peroxidase system--hypothiocyanous acid (HOSCN) and hypothiocyanite ions (OSCN-)--were generated by adding exogenous H2O2 to sterilized saliva containing endogenous peroxidases and thiocyanate (SCN-) ions. HOSCN/OSCN- generation was proportional to the amount of H2O2 added, and more HOSCN/OSCN- was detected in saliva at pH 7 than at pH 5. However, the growth of mutans streptococci and L. casei was inhibited at pH 5 by HOSCN/OSCN-, whereas no inhibition was found at pH 7. The findings show that (a) sufficient amount of HOSCN/OSCN- will inhibit the growth of cariogenic bacteria in human saliva at pH 5; (b) this amount of HOSCN/OSCN- can be generated in saliva by exogenously added H2O2; and (c) peroxidase systems have stronger antistreptococcal effects in human whole saliva than in phosphate buffer. PMID:1905532

  8. Tea and soybean extracts in combination with milk fermentation inhibit growth and enterocyte adherence of selected foodborne pathogens.

    PubMed

    Zhao, Danyue; Shah, Nagendra P

    2015-08-01

    This study examined the antibacterial and anti-adhesive properties of pure plant extracts (PPEs) of green tea (GT), black tea (BT) and soybean individually or in combination with milk. Fermented phenolic enriched-milk (fPEM) was prepared by combining PPEs with milk and fermented with lactic acid bacteria. Antimicrobial activity of extracts was evaluated by broth-dilution and agar diffusion assay. Anti-adhesive property of extracts was evaluated in Caco-2 cell model. Results from antibacterial tests showed that PPEs exhibited a dose-dependent growth inhibitory effect. Tea extracts were more effective in inhibiting Gram-positive bacteria while soybean extract exhibited similar effects against all pathogens tested. For fPEM, although total phenolic contents decreased compared with those in PPEs, growth inhibitory effect of fPEM containing tea extracts was greatly enhanced. All extracts showed significant inhibition against pathogen adhesion to Caco-2 cells. In particular, adhesion inhibition against Staphylococcus aureus and Listeria monocytogenes was >89% when fPEM extracts were applied. PMID:25766833

  9. Mechanism of cinnamic acid-induced trypsin inhibition: a multi-technique approach.

    PubMed

    Zhang, Hongmei; Zhou, Qiuhua; Cao, Jian; Wang, Yanqing

    2013-12-01

    In order to investigate the association of the protease trypsin with cinnamic acid, the interaction was characterized by using fluorescence, UV-vis absorption spectroscopy, molecular modeling and an enzymatic inhibition assay. The binding process may be outlined as follows: cinnamic acid can interact with trypsin with one binding site to form cinnamic acid-trypsin complex, resulting in inhibition of trypsin activity; the spectroscopic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being -8.95 kJ mol(-1) and 50.70 J mol(-1) K(-1), respectively. Noncovalent interactions make the main contribution to stabilize the trypsin-cinnamic acid complex; cinnamic acid can enter into the primary substrate-binding pocket and alter the environment around Trp and Tyr residues. PMID:23954540

  10. Mechanism of cinnamic acid-induced trypsin inhibition: A multi-technique approach

    NASA Astrophysics Data System (ADS)

    Zhang, Hongmei; Zhou, Qiuhua; Cao, Jian; Wang, Yanqing

    2013-12-01

    In order to investigate the association of the protease trypsin with cinnamic acid, the interaction was characterized by using fluorescence, UV-vis absorption spectroscopy, molecular modeling and an enzymatic inhibition assay. The binding process may be outlined as follows: cinnamic acid can interact with trypsin with one binding site to form cinnamic acid-trypsin complex, resulting in inhibition of trypsin activity; the spectroscopic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being -8.95 kJ mol-1 and 50.70 J mol-1 K-1, respectively. Noncovalent interactions make the main contribution to stabilize the trypsin-cinnamic acid complex; cinnamic acid can enter into the primary substrate-binding pocket and alter the environment around Trp and Tyr residues.

  11. TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice.

    PubMed

    Hao, Chunhai; Song, Jin H; Hsi, Belinda; Lewis, Jamie; Song, Doyoun K; Petruk, Kenneth C; Tyrrell, David L J; Kneteman, Norman M

    2004-12-01

    Tumor necrosis factor (TNF) family ligand TNF-alpha and Fas ligand (FasL) can trigger apoptosis in solid tumors, but their clinical usage has been limited by hepatotoxicity. TNF-related apoptosis-inducing ligand (TRAIL) is a newly identified member of the TNF family, and its clinical application currently is under a similar debate. Here, we report a recombinant soluble form of human TRAIL (114 to 281 amino acids) that induces apoptosis in tumor cells but not human hepatocytes. We first isolated human hepatocytes from patients and showed that the human hepatocytes expressed Fas but no TRAIL death receptor DR4 and little DR5 on the cell surface. Antibody cross-linked FasL, but not TRAIL, triggered apoptosis of the human hepatocytes through cleavage of caspases. We then examined TRAIL hepatotoxicity in severe combined immunodeficient/Alb-uPA chimeric mice harboring human hepatocytes. Intravenous injection of FasL, but not TRAIL, caused apoptotic death of human hepatocytes within the chimeric liver, thus killing the mice. Finally, we showed that repeated intraperitoneal injections of TRAIL inhibited intraperitoneal and subcutaneous tumor growth without inducing apoptosis in human hepatocytes in these chimeric mice. The results indicate that the recombinant soluble human TRAIL has a profound apoptotic effect on tumor cells but is nontoxic to human hepatocytes in vitro and in vivo. PMID:15574753

  12. Acid-catalyzed reactions of epoxides for atmospheric nanoparticle growth.

    PubMed

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

    2014-11-01

    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

  13. Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth.

    PubMed

    Kawabata, Naoya; Ijiri, Kosei; Ishidou, Yasuhiro; Yamamoto, Takuya; Nagao, Hiroko; Nagano, Satoshi; Maeda, Shingo; Komiya, Setsuro; Setoguchi, Takao

    2011-10-01

    The Hedgehog pathway functions as an organizer in embryonic development. Recent studies have shown that mutation of the PTCH1 gene involved in the Hedgehog pathway affects rhabdomyosarcoma development. However, the expression of Hedgehog pathway molecules in human rhabdomyosarcoma cells has not been well clarified. In addition, the effect of pharmacological inhibition of the Hedgehog pathway is not known. We investigated the expression of the genes involved in the Hedgehog pathway using human rhabdomyosarcoma cell lines and biopsy specimens. Further, we evaluated the effect of pharmacological inhibition of the Hedgehog pathway using cyclopamine or GANT61 by WST assay, cell proliferation assay and cell death detection assay. Real-time PCR revealed that human rhabdomyosarcoma cell lines and biopsy specimens overexpressed the following genes: Sonic hedgehog, Indian hedgehog, Desert hedgehog, PTCH1, SMO, GLI1, GLI2 and ULK3. Immunohistochemistry revealed that rhabdomyosarcoma cell lines and biopsy specimens expressed SMO and GLI2. Inhibition of SMO by cyclopamine slowed the growth of human rhabdomyosarcoma cell lines. Similarly, inhibition of GLI by GANT61 slowed the growth of human rhabdomyosarcoma cell lines. Inhibition of cell proliferation and apoptotic cell death together prevented the growth of rhabdomyosarcoma cells by cyclopamine and GANT61 treatment. Our findings suggest that pharmacological inhibition of the Hedgehog pathway may be a useful approach for treating rhabdomyosarcoma patients. PMID:21674124

  14. Eicosapentaenoic acid inhibits endothelial cell migration in vitro

    Microsoft Academic Search

    Laura Tonutti; Luca Manzi; Maria T Tacconi; Gianfranco Bazzoni

    2010-01-01

    Background  As n-3 Polyunsaturated Fatty Acids exert a beneficial action on the cardiovascular system, it is important to investigate their\\u000a effects on endothelial cell responses that (like migration) contribute to repairing vascular lesions.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  To this purpose, using functional and morphological in vitro assays, we have examined the effect of n-3 Polyunsaturated Fatty Acids on the migration of endothelial cells.\\u000a \\u000a \\u000a \\u000a \\u000a Results  We report

  15. Transforming growth factor-? inhibits nephronectin-induced osteoblast differentiation

    Microsoft Academic Search

    Ling Fang; Shireen Kahai; Weining Yang; Chengyan He; Arun Seth; Chun Peng; Burton B. Yang

    2010-01-01

    We used cDNA microarray to identify transforming growth factor beta (TGF-?) responsive target genes during osteoblast development and found that nephronectin (Npnt) is one such gene that is significantly down-regulated. Here we report the role of TGF-? in regulating Npnt-mediated osteoblast differentiation. We found that the effect of TGF-? on Npnt expression is associated with a change in cell morphology

  16. Activation of Liver X Receptors inhibits of Hedgehog signaling, clonogenic growth, and self-renewal in multiple myeloma

    PubMed Central

    Agarwal, Jasmin R.; Wang, Qiuju; Tanno, Toshihiko; Rasheed, Zeshaan; Merchant, Akil; Ghosh, Nilanjan; Borrello, Ivan; Huff, Carol Ann; Parhami, Farhad; Matsui, William

    2014-01-01

    The Hedgehog (Hh) signaling pathway is aberrantly activated in a wide variety of human cancers, and recent clinical studies have demonstrated that pathway inhibitors are effective in advanced basal cell carcinoma (BCC). The majority of these agents have been designed to target SMOOTHENED (SMO), a transmembrane regulator of Hh signaling, but subsequent mutations in SMO have been found to generate drug resistance. In other cancers, oncogenic events that bypass SMO may activate canonical Hh signaling, and SMO antagonists have not demonstrated significant activity in several diseases. Therefore, alternative strategies targeting the Hh pathway downstream of SMO may have clinical utility. Liver X Receptors (LXRs) regulate cholesterol and fatty acid homeostasis, and LXR activation can inhibit the Hh pathway in normal mouse embryonic fibroblasts. We examined the effects of LXR activation on Hh signaling in human multiple myeloma (MM) cells and found that LXR agonists inhibited Hh pathway activity and clonogenic tumor growth in vitro. LXR activation also inhibited putative MM cancer stem cells in vivo leading to the loss of tumor initiating and self-renewal potential. Finally, Hh signaling was inhibited downstream of SMO, suggesting that LXR agonists may represent a novel strategy to target pathogenic Hh signaling as well as treat MM. PMID:24807964

  17. Galbanic acid inhibits HIF-1? expression via EGFR/HIF-1? pathway in cancer cells.

    PubMed

    Eskandani, Morteza; Abdolalizadeh, Jalal; Hamishehkar, Hamed; Nazemiyeh, Hossein; Barar, Jaleh

    2015-03-01

    Hypoxia Inducible Factor-1 plays a key transcriptional role in the adaptation of hypoxic solid tumors to low oxygen environment. Here, we aimed to investigate galbanic acid (GBA) inhibitory effects on HIF-1 activation during hypoxia and normoxia. MTT survival and Annexin V assays were used to evaluate GBA cytotoxicity and apoptosis in treated cells. Quantitative real time PCR and western blotting were used to estimate mRNA expression and translated protein, respectively. Results showed that GBA dose- and time-dependently decreased the in vitro growth of OVCAR-3 human epithelial carcinoma cells with an IC50 of approximately 37, 12.1 and 10?M GBA at 24, 48 and 72h, respectively. Following phosphatidylserine of outer leaflet of the plasma membrane revealed occurrence of early/late apoptosis in GBA treated cells. In addition, we found that GBA down-regulates HIF-1? and HIF-1? mRNA expression in both hypoxia and normoxia. To determine the mechanism of action, we showed that GBA did not inhibit Akt and EGFR mRNA expression, yet protein degradation investigation showed that GBA shortened the half-life of EGFR through decreasing its stability with a decrease of nearly 2 and 3h in A549 and OVCAR-3 cell lines, respectively. We also found that downstream genes contributed in glycolysis, including Eno 1 and GluT-1, are underexpressed in GBA treated cells in hypoxia. Conclusively, GBA may inhibit HIF-1 activation through down-regulation of its subunit expression in hypoxia, and increasing of EGFR degradation in normoxia. PMID:25510323

  18. Ellagic acid & gallic acid from Lagerstroemia speciosa L. inhibit HIV-1 infection through inhibition of HIV-1 protease & reverse transcriptase activity

    PubMed Central

    Nutan; Modi, Manoj; Goel, Tanvi; Das, Tiyasa; Malik, Shweta; Suri, Samiksha; Rawat, Ajay Kumar Singh; Srivastava, Sharad Kumar; Tuli, Rakesh; Malhotra, Swadesh; Gupta, Satish Kumar

    2013-01-01

    Background & objectives: Banaba (Lagerstroemia speciosa L.) extracts have been used as traditional medicines and are effective in controlling diabetes and obesity. The aim of this study was to evaluate the anti-HIV property of the extracts prepared from the leaves and stems of banaba, and further purification and characterization of the active components. Methods: Aqueous and 50 per cent ethanolic extracts were prepared from leaves and stems of banaba and were evaluated for cytotoxicity and anti-HIV activity using in vitro reporter gene based assays. Further, three compounds were isolated from the 50 per cent ethanolic extract of banaba leaves using silica gel column chromatography and characterization done by HPLC, NMR and MS analysis. To delineate the mode of action of the active compounds, reverse transcriptase assay and protease assay were performed using commercially available kits. Results: All the extracts showed a dose dependent inhibition of HIV-1-infection in TZM-bl and CEM-GFP cell lines with a maximum from the 50 per cent ethanolic extract from leaves (IC50= 1 to 25 ?g/ml). This observation was confirmed by the virus load (p24) estimation in infected CEM-GFP cells when treated with the extracts. Gallic acid showed an inhibition in reverse transcriptase whereas ellagic acid inhibited the HIV-1 protease activity. Interpretation & conclusions: The present study shows a novel anti-HIV activity of banaba. The active components responsible for anti-HIV activity were gallic aci