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1

Calcite Crystal Growth Rate Inhibition by Polycarboxylic Acids  

Microsoft Academic Search

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

Michael M. Reddy; Anthony R. Hoch

2001-01-01

2

Calcite crystal growth rate inhibition by polycarboxylic acids  

USGS Publications Warehouse

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.

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

2001-01-01

3

Rapid growth inhibition of Avena coleoptile segments by abscisic Acid.  

PubMed

An angular position sensing transducer was used to make continuous measurements of elongation of a column of Avena sativa coleoptile segments. Elongation stimulated by 2 mum indoleacetic acid was inhibited by 0.1 mm abscisic acid with a latent period of about 4 or 5 minutes at pH 6.0, 30 C. Full growth inhibition was not established until about 1 hour after the addition of the abscisic acid. The same degree of final growth inhibition could be obtained under the above conditions using 10 muM and 1 muM abscisic acid, but the latent period was longer. Pretreatments with abscisic acid affected the growth rate but did not extend the latent period of a subsequent response to auxin. The short term kinetics of inhibition by abscisic acid were not similar to those of any of the inhibitors of RNA and protein synthesis tested in this system. PMID:16658304

Rehm, M M; Cline, M G

1973-01-01

4

Glycyrrhizic acid inhibits virus growth and inactivates virus particles  

Microsoft Academic Search

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

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

1979-01-01

5

Cinnamic Acid Increases Lignin Production and Inhibits Soybean Root Growth  

PubMed Central

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

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

2013-01-01

6

Gymnemic Acids Inhibit Hyphal Growth and Virulence in Candida albicans.  

PubMed

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

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

2013-09-11

7

(Aminooxy)acetic acid inhibits petunia growth and gibberellin- and cytokinin-stimulated growth in bioassays  

Microsoft Academic Search

(Aminooxy)acetic acid (AOA) was applied to greenhouse-grown petunias and was used in bioassays for three plant growth hormones\\u000a so that its growth regulator properties could be studied. In greenhouse studies foliar sprays of 4.8–12 mm AOA inhibited vegetative growth of petunia seedlings (Petunia xhybrida Vilm. ‘White Flash’). When gibberellin A 3 (GA3) was applied to shoot tips previously treated with

Philip E. Hammer; David S. Koranski; Richard J. Gladont

1995-01-01

8

EFFECTS OF SOME PLANT GROWTH REGULATORS ON JASMONIC ACID INDUCED INHIBITION OF SEED GERMINATION AND SEEDLING GROWTH OF BARLEY  

Microsoft Academic Search

The effects of gibberellic acid, kinetin, benzyladenine, ethylene, 24- epibrassinolide and polyamines (spermine, spermidine, putrescine, cadaverine) on jasmonic acid inhibition of seed germination and seedling growth of barley were studied. All of the plant growth regulators studied were determined to have a succesful performance in reversing of the inhibitory effects of jasmonic acid on the seed germination and seedling growth.

Kudret KABAR; Semra KILIÇ

9

Transient growth inhibition of Escherichia coli K-12 by ion chelators: "in vivo" inhibition of ribonucleic acid synthesis.  

PubMed Central

The ion chelators picolinic acid, quinaldic acid, 1,10-phenanthroline, and 8-hydroxyquinoline, but not ethylenediaminetetraacetate, ethyleneglycol-bis-(beta-aminoethyl ether)-N,N-tetraacetate, or dipicolinic acid, rapidly but transiently arrest growth of Escherichia coli K-12. Cells adapt and become resistant to growth inhibition by these agents, a process which requires protein synthesis. Mn2+, at low concentrations, decreases the time required for resumption of growth. Proteins synthesized during the lag are quantitatively and qualitatively different from those synthesized during normal growth. Inhibition of growth can explained by an effect on RNA polymerase, a known metalloenzyme. Images

Collins, J J; Alder, C R; Fernandez-Pol, J A; Court, D; Johnson, G S

1979-01-01

10

Transient growth inhibition of Escherichia coli K-12 by ion chelators: "in vivo" inhibition of ribonucleic acid synthesis.  

PubMed

The ion chelators picolinic acid, quinaldic acid, 1,10-phenanthroline, and 8-hydroxyquinoline, but not ethylenediaminetetraacetate, ethyleneglycol-bis-(beta-aminoethyl ether)-N,N-tetraacetate, or dipicolinic acid, rapidly but transiently arrest growth of Escherichia coli K-12. Cells adapt and become resistant to growth inhibition by these agents, a process which requires protein synthesis. Mn2+, at low concentrations, decreases the time required for resumption of growth. Proteins synthesized during the lag are quantitatively and qualitatively different from those synthesized during normal growth. Inhibition of growth can explained by an effect on RNA polymerase, a known metalloenzyme. PMID:110773

Collins, J J; Alder, C R; Fernandez-Pol, J A; Court, D; Johnson, G S

1979-06-01

11

Polyunsaturated fatty acids inhibit melanoma cell growth in vitro.  

PubMed

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

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

12

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

Microsoft Academic Search

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

DaZhi Chen; Karen Auborn

13

Retinoic Acid Receptor ? Mediates Growth Inhibition by Retinoids in Human Colon Carcinoma HT29 Cells  

Microsoft Academic Search

Although retinoids have been suggested to inhibit chemically induced colon carcinogenesis, the molecular mechanisms underlying retinoid-mediated growth regulation in colon carcinoma cells are unknown. Therefore, we investigated the biological effects of retinoids on growth in HT29 colon carcinoma cells. All-trans retinoic acid (ATRA) treatment of HT29 cells resulted in a profound inhibition of anchorage-independent growth without biochemical or morphological evidence

Barbara Nicke; Astrid Kaiser; Bertram Wiedenmann; Ernst-Otto Riecken; Stefan Rosewicz

1999-01-01

14

Inhibition of mycelia growth and norsolorinic acid accumulation of Aspergillus parasiticus by peanut seed endophytic bacteria  

Microsoft Academic Search

Control of peanut infection by aflatoxins is a worldwide problem. In this paper, five endophytic bacteria strains isolated from peanut seeds were assayed for their inhibition to mycelia growth and norsolorinic acid accumulation using Aspergillus parasiticus NA mutant as indicated strain. Results showed four bacteria had higher inhibition ability on PGY media contained the extract of peanut seeds than on

Li Qian-Wei; Yan Pei-Sheng; Wu Han-Qi; Wang Kai

2011-01-01

15

Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes  

PubMed Central

Polyunsaturated fatty acids (PUFAs) possess anti-cancer action both in vitro and in vivo. In the present study, we detected cell viability with methyl thiazolyl tetrazolium (MTT) assay and cell membrane permeability with propidium iodide (PI) fluorescence dyeing, and calculated cell membrane fluidity change as fluorescence anisotropy. Fatty acid content in cells was measured by gas chromatography/mass spectroscopy (GC/MS), and the relationship between fatty acid composition and cell viability was studied. We observed that n-6 PUFA linoleic acid (LA) inhibited tumor cell growth at high concentrations (?300 µmol/L), while low concentrations (100–200 µmol/L) seemed to promote cell proliferation. Analyses of cell membrane permeability, cell membrane fluidity, and cell fatty acid composition suggested that the anti-cancer action of LA could be related to changes in the ratio of n-6 to n-3 PUFAs. We observed that pre-incubation of cancer cells with 100 µmol/L LA for 24 h enhanced cell sensitivity to the cytotoxic action of LA, whereas undifferentiated cell line LoVo seemed to have a distinct path in LA-induced death. These results showed that one of the mechanisms by which supplementation of LA induces cancer cell death could be altering the ratio of n-6/n-3 PUFAs, and this may be related to cell differentiation status.

Lu, Xiao-feng; He, Guo-qing; Yu, Hai-ning; Ma, Qi; Shen, Sheng-rong; Das, Undurti N.

2010-01-01

16

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

PubMed

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

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

2010-09-17

17

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

PubMed Central

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.

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

2010-01-01

18

Auxin-induced ethylene triggers abscisic acid biosynthesis and growth inhibition.  

PubMed

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 [(3)H]-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

Hansen, H; Grossmann, K

2000-11-01

19

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

USGS Publications Warehouse

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.

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

2000-01-01

20

Volatile Fatty Acids andtheInhibition ofEscherichia coli Growth byRumenFluid1  

Microsoft Academic Search

Concentrations ofvolatile fatty acids (VFA)normally found inbovine rumen fluid inhibited growth ofEscherichia coil inAntibiotic Medium3.Acetic, propionic, and butyric acids eachproduced growth inhibition which was markedly pH-dependent. Little inhibition was observed atpH 7.0, andinhibition increased withdecreasing pH.Acombination of60jmolesofacetate, 20 Mmolesofpropionate, and15\\/Lmoles ofbutyrate permlgave96,69,and2%inhibition atpH6.0, 6.5, and7.0, respectively. Rumenfluid (50%) gave89and48% inhibition atpH6.0and6.5, respectively, and growthstimulation (22%)atpH 7.0. Rumenfluid inhibitory activity was

MEYER J. WOLIN

21

L-type amino acid transporter 1 inhibitors inhibit tumor cell growth.  

PubMed

Most tumor cell membranes overexpress L-type amino acid transporter 1, while normal cell membranes contain l-type amino acid transporter 2; both are Na(+)-independent amino acid transporters. Therefore, compounds that selectively inhibit L-type amino acid transporter 1 offer researchers with a novel cancer molecular target. Synthetic chemistry efforts and in vitro screening have produced a variety of novel compounds possessing high in vitrol-type amino acid transporter 1 selectivity; KYT-0353 was one such compound. The present studies illustrate that KYT-0353 inhibited (14)C-leucine uptake and cell growth in human colon cancer-derived HT-29 cells; IC(50)s were 0.06 microm and 4.1 microm, respectively. KYT-0353 also inhibited (14)C-leucine uptake in mouse renal proximal tubule cells expressing l-type amino acid transporter 1, and inhibited cell growth; IC(50)s were 0.14 microm and 16.4 microm, respectively. Compared to control animals, intravenously administered KYT-0353 (12.5 mg/kg and 25.0 mg/kg) showed statistically significant growth inhibition against HT-29 tumors transplanted to nude mice with maximal inhibition ratios of 65.9% and 77.2%, respectively. Body weight increase with time--a safety indicator--was slightly depressed at 12.5 mg/kg and 25.0 mg/kg with maximal ratios of 3.7% (day 2) and 6.3% (day 11), respectively. Thus, KYT-0353 showed significant growth inhibitory effects on HT-29 cells both in vitro and in vivo, whereas it only caused a slight body weight depression. Therefore, KYT-0353 appears to have potential as a novel anti-tumor agent, presumably via selective in vivol-type amino acid transporter 1 inhibition. PMID:19900191

Oda, Koji; Hosoda, Noriko; Endo, Hiroshi; Saito, Kunio; Tsujihara, Kenji; Yamamura, Michio; Sakata, Takeshi; Anzai, Naohiko; Wempe, Michael F; Kanai, Yoshikatsu; Endou, Hitoshi

2009-10-08

22

Inhibition of the synthesis of cell wall polysaccharides in oat coleoptile segments by jasmonic acid: Relevance to its growth inhibition  

Microsoft Academic Search

The inhibitory mode of action of jasmonic acid (JA) on the growth of etiolated oat (Avena sativa L. cv. Victory) coleoptile segments was studied in relation to the synthesis of cell wall polysaccharides using [14C]glucose. Exogenously applied JA significantly inhibited indoleacetic acid (IAA)-induced elongation of oat coleoptile segments\\u000a and prevented the increase of the total amounts of cell wall polysaccharides

Junichi Ueda; Kensuke Miyamoto; Seiichiro Kamisaka

1995-01-01

23

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

PubMed

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

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

2012-05-11

24

Fatty acids and monoacylglycerols inhibit growth of Staphylococcus aureus  

Microsoft Academic Search

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

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

2006-01-01

25

Influence of Medium Buffering Capacity on Inhibition of Saccharomyces cerevisiae Growth by Acetic and Lactic Acids  

PubMed Central

Acetic acid (167 mM) and lactic acid (548 mM) completely inhibited growth of Saccharomyces cerevisiae both in minimal medium and in media which contained supplements, such as yeast extract, corn steep powder, or a mixture of amino acids. However, the yeast grew when the pH of the medium containing acetic acid or lactic acid was adjusted to 4.5, even though the medium still contained the undissociated form of either acid at a concentration of 102 mM. The results indicated that the buffer pair formed when the pH was adjusted to 4.5 stabilized the pH of the medium by sequestering protons and by lessening the negative impact of the pH drop on yeast growth, and it also decreased the difference between the extracellular and intracellular pH values (?pH), the driving force for the intracellular accumulation of acid. Increasing the undissociated acetic acid concentration at pH 4.5 to 163 mM by raising the concentration of the total acid to 267 mM did not increase inhibition. It is suggested that this may be the direct result of decreased acidification of the cytosol because of the intracellular buffering by the buffer pair formed from the acid already accumulated. At a concentration of 102 mM undissociated acetic acid, the yeast grew to higher cell density at pH 3.0 than at pH 4.5, suggesting that it is the total concentration of acetic acid (104 mM at pH 3.0 and 167 mM at pH 4.5) that determines the extent of growth inhibition, not the concentration of undissociated acid alone.

Thomas, K. C.; Hynes, S. H.; Ingledew, W. M.

2002-01-01

26

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

Microsoft Academic Search

Locked nucleic acids (LNA) are novel high-affinity DNA analogs that can be used as genotype-specific drugs. The LNA oligonucleotides (LNA PO ODNs) are very stable in vitro and in vivo without the need for a phosphorothiolated backbone. In this study we tested the biological fate and the efficacy in tumor growth inhibition of antisense oligonucleotides dir- ected against the gene

Kees Fluiter; Asbroek ten A. L. M. A; Wissel de M. B; Marja E. Jakobs; Margit Wissenbach; H. Olsson; O. Olsen; H. Oerum; F. Baas

2003-01-01

27

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

PubMed

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

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

2013-04-03

28

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

PubMed Central

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

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

2013-01-01

29

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

Microsoft Academic Search

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

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

2005-01-01

30

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

PubMed

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

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

2007-10-01

31

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

Microsoft Academic Search

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

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

1985-01-01

32

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

PubMed Central

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

Montague, M. J.

1993-01-01

33

Ellagic acid inhibits human pancreatic cancer growth in Balb c nude mice.  

PubMed

Ellagic acid (EA) is a polyphenol found in several plants and fruits. The objectives of this study were to examine the molecular mechanisms by which EA inhibits pancreatic cancer growth in Balb C nude mice. PANC-1 cells were injected subcutaneously into Balb c nude mice, and tumor-bearing mice were treated with EA. The expression of Akt, Shh and Notch and their target gene products were measured by the immunohistochemistry and Western blot analysis. Treatment of PANC-1 xenografted mice with EA resulted in significant inhibition in tumor growth which was associated with suppression of cell proliferation and caspase-3 activation, and induction of PARP cleavage. EA inhibited the expression of Bcl-2, cyclin D1, CDK2, and CDK6, and induced the expression of Bax in tumor tissues compared to untreated control group. EA inhibited the markers of angiogenesis (COX-2, HIF1?, VEGF, VEGFR, IL-6 and IL-8), and metastasis (MMP-2 and MMP-9) in tumor tissues. Furthermore, treatment of mice with EA caused a significant inhibition in phospho-Akt, Gli1, Gli2, Notch1, Notch3, and Hey1. EA also reversed epithelial to mesenchymal transition by up-regulating E-cadherin and inhibiting the expression of Snail, MMP-2 and MMP-9. These data suggest that EA can inhibit pancreatic cancer growth, angiogenesis and metastasis by suppressing Akt, Shh and Notch pathways. In view of the fact that EA could effectively inhibit human pancreatic cancer growth by suppressing Akt, Shh and Notch pathways, our findings suggest that the use of EA would be beneficial for the management of pancreatic cancer. PMID:23684930

Zhao, Min; Tang, Su-Ni; Marsh, Justin L; Shankar, Sharmila; Srivastava, Rakesh K

2013-05-16

34

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

Microsoft Academic Search

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

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

2006-01-01

35

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

PubMed

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

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

2005-03-01

36

OMEGA-3 POLYUNSATURATED FATTY ACIDS INHIBIT HEPATOCELLULAR CARCINOMA CELL GROWTH THROUGH BLOCKING ?-CATENIN AND COX-2  

PubMed Central

Hepatocellular carcinoma (HCC) is a common human cancer with high mortality and currently there is no effective chemoprevention or systematic treatment. Recent evidence suggests that COX-2-derived PGE2 and Wnt/?-catenin signaling pathways are implicated in hepatocarcinogenesis. Here we report that ?-3 PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), inhibit HCC growth through simultaneously inhibition of COX-2 and ?-catenin. DHA and EPA treatment resulted in a dose-dependent reduction of cell viability with cleavage of PARP, caspase-3 and caspase-9 in three human HCC cell lines (Hep3B, Huh-7, HepG2). In contrast, arachidonic acid (AA), a ?-6 PUFA, exhibited no significant effect. DHA and EPA treatment caused dephosphorylation and thus activation of GSK-3?, leading to ?-catenin degradation in Hep3B cells. The GSK3-? inhibitor, LiCl, partially prevented DHA-induced ?-catenin protein degradation and apoptosis. Additionally, DHA induced the formation of ?-catenin/Axin/GSK-3? binding complex, which serves as a parallel mechanism for ?-catenin degradation. Furthermore, DHA inhibited PGE2 signaling through downregulation of COX-2 and upregulation of the COX-2 antagonist, 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Finally, the growth of HCC in vivo was significantly reduced when mouse HCCs (Hepa1–6) were inoculated into the Fat-1 transgenic mice which express a Caenorhabditis elegans desaturase converting ?-6 to ?-3 PUFAs endogenously. These findings provide important preclinical evidence and molecular insight for utilization of ?-3 PUFAs for the chemoprevention and treatment of human HCC.

Lim, Kyu; Han, Chang; Dai, Yifan; Shen, Miaoda; Wu, Tong

2009-01-01

37

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

PubMed

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

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

2010-04-11

38

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

PubMed Central

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

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

2003-01-01

39

Chimeric retinoic acid/thyroid hormone receptors implicate RAR-alpha 1 as mediating growth inhibition by retinoic acid.  

PubMed Central

Retinoic acid (RA) affects the growth and differentiation of cells in culture, usually to decrease the growth rate. In amphibian limb regeneration RA has the remarkable ability to affect pattern formation by changing positional identity, but its initial action on the limb is to inhibit division of the blastemal progenitor cells. Newt limb blastemal cells also show this inhibition in culture. In order to investigate the role of different RA receptors (RARs) in the RA response, the hormone binding domain of the newt RARs alpha 1 and delta 1 was replaced with the corresponding region from the Xenopus thyroid hormone receptor-alpha (TR-alpha). In COS cells transfected with each of the chimeras, transcription was activated after exposure to thyroid hormone (T3). Their profile of activity on three different response elements was indicative of RAR specificity and not TR specificity. After transfection of cultured newt blastemal cells with a DNA particle gun, the chimeras were equally active in stimulating T3-dependent transcription of two different synthetic reporter genes. Blastemal cells were transfected with chimeras or control plasmids along with a marker plasmid expressing beta-galactosidase, exposed to RA or T3 and labelled with [3H]thymidine followed by autoradiography. The alpha 1 chimera gave T3-dependent inhibition of growth, comparable to the effect exerted by RA itself, whereas the delta 1 chimera and control plasmids were inactive. The results imply that RAR-alpha 1 mediates the effects of RA on blastemal cell growth. Images

Schilthuis, J G; Gann, A A; Brockes, J P

1993-01-01

40

Nordihydroguaiaretic acid inhibits transforming growth factor ? type 1 receptor activity and downstream signaling  

PubMed Central

It has been well documented that nordihydroguaiaretic acid (NDGA), a phenolic lignan isolated from the creosote bush, Larrea tridentate, has anti-cancer activity in vitro and in vivo. Several mechanisms have been identified that could contribute to these actions, as NDGA directly inhibits metabolic enzymes and receptor tyrosine kinases that are established anti-cancer targets. In the present study, we show that NDGA inhibits the transforming growth factor ? (TGF-?) type I receptor, a serine threonine kinase receptor. In cultured cells, NDGA treatment repressed Smad2 phosphorylation induced by TGF-? treatment and by a constitutively active mutant of TGF-? type I receptor (T202D). NDGA also inhibited downstream transcriptional activation mediated by both TGF-? treatment and the constitutively active mutant receptor. In vitro, NDGA inhibited TGF-? type I receptor mediated Smad2 phosphorylation in crude cell lysates and in a purified preparation. Importantly, screening select analogs demonstrated that modification of NDGA’s structure resulted in altered potency against the receptor. These results indicated that the structure of NDGA can be modified to achieve increased potency. Together our data provide a novel mechanism for NDGA activity which could help explain its anti-cancer activity, and suggest that NDGA could serve as a structural motif for developing serine/threonine kinase inhibitors with selectivity for TGF-? type I receptor.

Li, Fusheng; Anderson, Marc O.; Youngren, Jack F.

2009-01-01

41

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

PubMed

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

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

2010-08-10

42

Triclosan inhibition of fatty acid synthesis and its effect on growth of Escherichia coli and Pseudomonas aeruginosa  

Microsoft Academic Search

Conclusions: This study shows that the inhibition of fatty acid biosynthesis by the bisphenol might be involved in its growth-inhibitory action and that other mechanisms are involved in its lethal effect. In addition, although microorganisms with a high triclosan MIC were still susceptible to the inhibitory effect of the bisphenol on fatty acid biosynthesis, a higher concentration of the compound

Margarita Gomez Escalada; J. L. Harwood; J.-Y. Maillard; D. Ochs

2005-01-01

43

Induction of retinoic acid receptor ? mediates growth inhibition in retinoid resistant human colon carcinoma cells  

Microsoft Academic Search

BACKGROUNDThe molecular mechanisms underlying the differential sensitivity of human colon carcinoma cells to retinoid mediated growth inhibition are poorly understood.AIMTo identify the intracellular mechanisms responsible for resistance against retinoid mediated growth inhibition in human colon carcinoma cells.METHODSAnchorage independent growth of the human colon carcinoma cell lines HT29 and LoVo was determined by a human tumour clonogenic assay. Retinoid receptor expression

B Nicke; E-O Riecken; S Rosewicz

1999-01-01

44

Induction of Mammary Differentiation by Mammary-derived Growth Inhibitor related Gene That Interacts with an v-3 Fatty Acid on Growth Inhibition of Breast Cancer Cells1  

Microsoft Academic Search

We previously identified and characterized a novel tumor growth inhibitor and a fatty acid-binding protein in human mammary gland and named it the mammary-derived growth inhibitor-related gene (MRG). Here, the effects of MRG on mammary gland differentiation and its interaction with v-3 polyunsaturated fatty acids (v-3 PUFAs) on growth inhibition were investigated. MRG protein expression was associated with human mammary

Mingsheng Wang; Yiliang E. Liu; Jian Ni; Banu Aygun; Itzhak D. Goldberg; Y. Eric Shi

2000-01-01

45

Suberoyl bishydroxamic acid inhibits the growth of A549 lung cancer cells via caspase-dependent apoptosis  

Microsoft Academic Search

Suberoyl bishydroxamic acid (SBHA) as a histone deacetylase (HDAC) inhibitor has various cellular effects such as cell growth\\u000a and apoptosis. In the present study, we evaluated the effects of SBHA on the growth and death of A549 lung cancer cells. SBHA\\u000a inhibited the growth of A549 cells with an IC50 of approximately 50 ?M at 72 h in a dose-dependent manner. DNA

Bo Ra You; Woo Hyun Park

2010-01-01

46

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

PubMed Central

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

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

2001-01-01

47

Insulin-like Growth Factor Binding Protein 3 Mediates Retinoic Acid and Transforming Growth Factor \\/32-induced Growth Inhibition in Human Breast Cancer Cells1  

Microsoft Academic Search

Retinoic acid (RA) is a potent in vitro inhibitor of cell proliferation in various malignant cell lines. The exact mechanisms of its actions, however, are not fully understood. To further elucidate the nature of this inhibition, we investigated the effects of RA in an estrogen receptor-negative human breast cancer cell line, MDA-MB-231. RA (0.01-5 \\/UM)significantly in hibited MDA-MB-231 cell growth

Zoran S. Gucev; Youngman Oh; Kevin M. Kelley; Ron G. Rosenfeld

48

Inhibition of carcinoma and melanoma cell growth by type 1 transforming growth factor beta is dependent on the presence of polyunsaturated fatty acids.  

PubMed Central

Improved serum-free media were developed for the anchorage-dependent growth of A549 human lung carcinoma and B16 mouse melanoma cell lines in vitro. Type 1 transforming growth factor beta (TGF-beta 1) inhibited the growth of A549 or B16 cells under serum-free conditions or in the presence of 10% serum by 15-33%. In contrast, in the presence of micrograms/ml concentrations of polyunsaturated fatty acids (PUFAs), picomolar concentrations of TGF-beta 1 irreversibly inhibited the serum-free growth of A549 or B16 cells by 90-100%. The PUFAs alone had little effect on cell growth. Cell growth inhibition by TGF-beta 1 was not potentiated by saturated fatty acids, monounsaturated fatty acids, or prostaglandins. Inhibition of A549 or B16 cell growth by TGF-beta 1 in the presence of PUFAs was almost completely reversed by the antioxidant vitamin E, suggesting a role for lipid peroxidation in this process. Inhibition of A549 or B16 cell growth by TGF-beta 1 in the presence of 5% fetal calf serum was also potentiated by PUFAs and partially reversed by antioxidants. The presence of retinoic acid was required for maximal PUFA-dependent growth inhibition of A549 or B16 cells by TGF-beta 1 under some, but not all, conditions. These results suggest that inhibition of carcinoma and melanoma cell growth by TGF-beta 1 is mediated, in large part, by PUFAs. Images

Newman, M J

1990-01-01

49

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...

50

Retinoic Acid Inhibits Cell Growth in HPV Negative Cervical Carcinoma Cells by Induction of Insulin-like Growth Factor Binding Protein5 (IGFBP-5) Secretion  

Microsoft Academic Search

Retinoids have been demonstrated to inhibit epithelial cell growth and differentiation. We examined the anti-proliferative effects of retinoic acid (RA) in an HPV positive and negative cervical carcinoma cell line. Our findings indicate that HPV-negative C33A cervical carcinoma cells are more sensitive to the growth inhibitory activity of retinoic acid (RA) than are HPV-positive CaSki cervical carcinoma cells. However, conditioned

Hiromi Higo; Cunming Duan; David R. Clemmons; Brian Herman

1997-01-01

51

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

PubMed Central

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

Killmer, John; Widholm, Jack; Slife, Fred

1981-01-01

52

Gallic acid inhibits the growth of HeLa cervical cancer cells via apoptosis and\\/or necrosis  

Microsoft Academic Search

Gallic acid (GA) is widely distributed in various plants and foods, and its various biological effects have been reported. Here, we evaluated the effects of GA on HeLa cells in relation to cell growth inhibition and death. HeLa cell growth was diminished with an IC50 of approximately 80?M GA at 24h whereas an IC50 of GA in human umbilical vein

Bo Ra You; Hwa Jin Moon; Yong Hwan Han; Woo Hyun Park

2010-01-01

53

The retinoic acid receptor antagonist, BMS453, inhibits normal breast cell growth by inducing active TGF? and causing cell cycle arrest  

Microsoft Academic Search

We have previously shown that a retinoic acid receptor (RAR) antagonist BMS453, which does not activate RAR-dependent gene transcription in breast cells, inhibits normal breast cell growth. In this study we have investigated the mechanisms by which this retinoid receptor antagonist inhibits cell growth. Both all trans retinoic acid (atRA) and BMS453 inhibited the proliferation of normal breast cell growth

Limin Yang; Jacek Ostrowski; Peter Reczek; Powel Brown

2001-01-01

54

Exogenous caffeic acid inhibits the growth and enhances the lignification of the roots of soybean (Glycine max).  

PubMed

The allelopathic effect of caffeic acid was tested on root growth, phenylalanine ammonia-lyase (PAL) and peroxidase (POD) activities, hydrogen peroxide (H(2)O(2)) accumulation, lignin content and monomeric composition of soybean (Glycine max) roots. We found that exogenously applied caffeic acid inhibited root growth, decreased the PAL activity and H(2)O(2) content and increased the soluble and cell wall-bound POD activities. The p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) monomers and total lignin (H+G+S) increased in the caffeic acid-exposed roots. When applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H), caffeic acid equalized the inhibitory effect of PIP, whereas the application of methylene dioxocinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL) plus caffeic acid decreased lignin production. These results indicate that exogenously applied caffeic acid can be channeled into the phenylpropanoid pathway via the 4CL reaction, resulting in an increase of lignin monomers that solidify the cell wall and inhibit root growth. PMID:21489652

Bubna, Gisele Adriana; Lima, Rogério Barbosa; Zanardo, Daniele Yara Lucca; Dos Santos, Wanderley Dantas; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

2011-04-12

55

Saussurea lappa inhibits the growth, acid production, adhesion, and water-insoluble glucan synthesis of Streptococcus mutans.  

PubMed

In the present study, inhibitory effects of the ethanol extract of Saussurea lappa (S. lappa) on the growth, acid production, adhesion, and water-insoluble glucan synthesis of Streptococcus mutans (S. mutans) were examined. The growth and acid production of Streptococcus mutans were inhibited by the presence of ethanol extract of Saussurea lappa (0.5-4 mg/ml) significantly. The ethanol extract of Saussurea lappa (0.25-4 mg/ml) also significantly lowered the adherence of Streptococcus mutans in a dose dependent manner. In water-insoluble glucan synthesis assay, 2-4 mg/ml of the ethanol extract of Saussurea lappa significantly inhibited the formation of water-insoluble glucan. These results suggest that Saussurea lappa may inhibit the caries-inducing properties of Streptococcus mutans. Further studies are necessary to clarify the active constituents of Saussurea lappa responsible for such biomolecular activities. PMID:17234374

Yu, Hyeon-Hee; Lee, Jun-Sup; Lee, Ki-Hyun; Kim, Ki-Young; You, Yong-Ouk

2006-12-14

56

Plant Lectin Can Target Receptors Containing Sialic Acid, Exemplified by Podoplanin, to Inhibit Transformed Cell Growth and Migration  

PubMed Central

Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by ?2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin receptor podoplanin (PDPN) is highly O-glycosylated with ?2,3-sialic acid linked to galactose. PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. Dietary lectins that target proteins containing ?2,3-sialic acid inhibit tumor cell growth. However, anti-cancer lectins that have been examined thus far target receptors that have not been identified. We report here that a lectin from the seeds of Maackia amurensis (MASL) with affinity for O-linked carbohydrate chains containing sialic acid targets PDPN to inhibit transformed cell growth and motility at nanomolar concentrations. Interestingly, the biological activity of this lectin survives gastrointestinal proteolysis and enters the cardiovascular system to inhibit melanoma cell growth, migration, and tumorigenesis. These studies demonstrate how lectins may be used to help develop dietary agents that target specific receptors to combat malignant cell growth.

Shen, Yongquan; Acharya, Nimish K.; Han, Min; McNulty, Dean E.; Hasegawa, Hitoki; Hyodo, Toshinori; Senga, Takeshi; Geng, Jian-Guo; Kosciuk, Mary; Shin, Seung S.; Goydos, James S.; Temiakov, Dmitry; Nagele, Robert G.; Goldberg, Gary S.

2012-01-01

57

Retinoic acid receptor antagonist BMS453 inhibits the growth of normal and malignant breast cells without activating RAR–dependent gene expression  

Microsoft Academic Search

To elucidate the role of RAR–dependent gene transcription in inhibiting breast cell growth, we have investigated the ability of retinoids to suppress growth of normal, immortal, and malignant breast cells. We compared the ability of alltrans retinoic acid (atRA) to activate retinoid receptors in normal, immortal, and malignant breast cells, with its ability to inhibit the growth of these cells.

L. Yang; H. T. Kim; J. Ostrowski; P. Reczek; P. H. Brown

1999-01-01

58

Unsaturated fatty acid requirement in Escherichia coli: mechanism of palmitate-induced inhibition of growth of strain WN1.  

PubMed

The minimum requirement for unsaturated fatty acids was investigated in E. coli using a mutant impaired in the synthesis of vaccenic acid. Exogenously supplied palmitic acid was incorporated by this mutant which led to a reduction in the proportion of cellular unsaturated fatty acids. Growth was impaired as the level of saturated fatty acids approached 76% at 37 degree C and 60% at 30 degree C. The basis of this growth inhibition was investigated. Most transport systems and enzymes examined remained active in palmitate-grown cells although the specific activities of glutamate uptake and succinic dehydrogenase were depressed 50%. Fluorescent probes of membrane organization indicated that fluidity decreased with palmitate incorporation. Temperature scans with parinaric acid indicated that rigid lipid domains exist in palmitate-grown cells at their respective growth temperature. Freeze-fracture electron microscopy confirmed the presence of phase separations (particle-free areas) in palmitate-grown cells held at their growth temperature prior to quenching. The extent of this separation into particle-free and particle-enriched domains was equivalent to that induced by a shift to 0 degree C in control cells. The incorporation of palmitate increased nucleotide leakage over threefold. The cytoplasmic enzyme beta-galactosidase was released into the surrounding medium as the concentration of unsaturated fatty acid approached the minimum for a particular growth temperature. Lysis was observed as a decrease in turbidity when cells which had been grown with palmitate were shifted a lower growth temperature. From these results we propose that leakage and partial lysis are the major factors contributing to the apparent decrease in growth rate caused by the excessive incorporation of palmitate. Further, we propose that membrane integrity may determine the minimum requirement for unsaturated fatty acids in E. coli rather than a specific effect on membrane transport and/or membrane-bound enzymes. PMID:7035675

Ingram, L O; Eaton, L C; Erdos, G W; Tedder, T F; Vreeland, N L

1982-01-01

59

Induction of mammary differentiation by mammary-derived growth inhibitor-related gene that interacts with an omega-3 fatty acid on growth inhibition of breast cancer cells.  

PubMed

We previously identified and characterized a novel tumor growth inhibitor and a fatty acid-binding protein in human mammary gland and named it the mammary-derived growth inhibitor-related gene (MRG). Here, the effects of MRG on mammary gland differentiation and its interaction with omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on growth inhibition were investigated. MRG protein expression was associated with human mammary gland differentiation, with the highest expression observed in the differentiated alveolar mammary epithelial cells from the lactating gland. Overexpression of MRG in human breast cancer cells induced differentiation with changes in cellular morphology and a significant increase in the production of lipid droplets. Treatment of mouse mammary gland in organ culture with MRG protein resulted in a differentiated morphology and stimulation of beta-casein expression. Treatment of human breast cancer cells with the omega-3 PUFA docosahexaenoic acid resulted in a differential growth inhibition proportional to their MRG expression. MRG-transfected cells or MRG protein treated cells were much more sensitive to docosahexaenoic acid-induced growth inhibition than MRG-negative or untreated control cells. Our results suggest that MRG is a candidate mediator of the differentiating effect of pregnancy on breast epithelial cells and may play a major role in omega-3 PUFA-mediated tumor suppression. PMID:11103817

Wang, M; Liu, Y E; Ni, J; Aygun, B; Goldberg, I D; Shi, Y E

2000-11-15

60

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

PubMed Central

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.

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

1983-01-01

61

Isogambogenic acid inhibits tumour angiogenesis by suppressing Rho GTPases and vascular endothelial growth factor receptor 2 signalling pathway.  

PubMed

Isogambogenic acid (iso-GNA) is a well-known herbal medicine extracted from Garcinia hanburyi. Although it is thought to have anti-tumour effects, its function is still unknown. This study carried out in vitro and in vivo evaluations of the anti-tumour and anti-angiogenic activity of iso-GNA and underlying mechanisms. A standard methyl thiazolyl tetrazolium assay showed that iso-GNA was more effective in inhibiting the proliferation of human umbilical vascular endothelial cells than A549 cancer cells. Iso-GNA demonstrated potent anti-angiogenic activity and low toxicity at appropriate concentrations in zebrafish embryos. In a xenograft nude mouse model of lung tumour, iso-GNA effectively inhibited tumour growth and tumour angiogenesis. Iso-GNA suppressed neovascularization of implanted matrigel plugs in vivo and inhibited vascular endothelial growth factor (VEGF)-induced microvessel sprouting from mouse aortic rings ex vivo. Iso-GNA inhibited VEGF-induced migration, invasion, and tube formation in vitro and affected cytoskeletal rearrangement in human umbilical vascular endothelial cells. The results show that iso-GNA suppressed angiogenesis-mediated tumour growth by targeting VEGFR2, Akt, mitogen-activated protein kinase, Rho GTPase, vascular endothelium-cadherin, and focal adhesion kinase signalling pathways. Together, these data suggest that iso-GNA inhibits angiogenesis and may be a viable drug candidate in anti-angiogenesis and anti-cancer therapies. PMID:24070138

Fan, Yi; Peng, Aihua; He, Shichao; Shao, Ximing; Nie, Chunlai; Chen, Lijuan

2013-01-01

62

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

PubMed Central

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.

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

2013-01-01

63

Conjugated Linoleic Acid (CLA) inhibits expression of the Spot 14 (THRSP) and fatty acid synthase genes and impairs the growth of human breast cancer and liposarcoma cells  

PubMed Central

Spot 14 (THRSP, S14) is a nuclear protein involved in the regulation of genes required for fatty acid synthesis in normal and malignant mammary epithelial and adipose cells. Havartine and Bauman reported that conjugated linoleic acid (CLA) inhibits S14 gene expression in bovine mammary and mouse adipose tissues, and reduces milk fat production in cows. We hypothesized that CLA inhibits S14 gene expression in human breast cancer and liposarcoma cells, and that this will retard their growth. Exposure of T47D breast cancer cells to a mixture of CLA isomers reduced the expression of the S14 and fatty acid synthase (FAS) genes. The mixture caused a dose-related inhibition of T47D cell growth, as did pure c9, t11- and t10, c12-CLA, but not linoleic acid. Similar effects were observed in MDA-MB-231 breast cancer cells. Provision of 8 ?M palmitate fully (CLA mix, t10, c12-CLA) or partially (c9, t11-CLA) reversed the antiproliferative effect in T47D cells. CLA likewise suppressed levels of S14 and FAS mRNAs in liposarcoma cells, and caused growth inhibition that was prevented by palmitic acid. CLA did not affect the growth of nonlipogenic HeLa cells or human fibroblasts. We conclude that, as in bovine mammary and mouse adipose cells, CLA suppresses S14 and FAS gene expression in human breast cancer and liposarcoma cells. Rescue from the antiproliferative effect of CLA by palmitic acid indicates that reduced tumor lipogenesis is a major mechanism for the anticancer effects of CLA.

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

2010-01-01

64

Conjugated eicosapentaenoic acid (EPA) inhibits transplanted tumor growth via membrane lipid peroxidation in nude mice.  

PubMed

Both conjugated linoleic acid (CLA) and eicosapentaenoic acid (EPA) have an antitumor effect. Hence, we hypothesized that a combination of conjugated double bonds and an (n-3) highly unsaturated fatty acid would produce stronger bioactivity. To verify the antitumor effect of conjugated EPA (CEPA), we transplanted DLD-1 human colon tumor cells into nude mice, and compared the tumor growth between CEPA-fed mice and CLA- and EPA-fed mice. After tumor cell inoculation, mice were assigned to 1 of 4 groups (control, CLA, EPA, and CEPA) consisting of 10 mice each. The control group received only safflower oil fatty acids, whereas the remaining groups received a mixture of safflower oil fatty acids and 20 g/100 g of total fatty acids as CLA, EPA, or CEPA. Mice were fed once every 2 d for 4 wk at a dose of 50 mg/mouse at each feeding. After 4 wk, tumor growth in CEPA-fed mice was significantly suppressed, compared with that in CLA- (P < 0.005) and EPA-fed mice (P < 0.001). DNA fragmentation in the tumor tissues of the CEPA-fed mice occurred more frequently than in the CLA- (P < 0.001) and EPA-fed mice (P < 0.001), suggesting that CEPA induced apoptosis in the tumor tissues. To further investigate the mechanism, the level of oxidative stress in the tumor tissues was determined. The CEPA-fed mice showed significant lipid peroxidation, compared with the CLA- (P < 0.001) and EPA-fed mice (P < 0.001). Therefore, we verified that CEPA has a stronger in vivo antitumor effect than EPA and CLA, and that CEPA acts through induction of apoptosis via lipid peroxidation. PMID:15113964

Tsuzuki, Tsuyoshi; Igarashi, Miki; Miyazawa, Teruo

2004-05-01

65

Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis.  

PubMed

Valproic acid (VPA) as a histone deacetylase (HDAC) inhibitor has an anticancer effect. In the present study, we evaluated the effects of VPA on the growth and death of HeLa cervical cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH). Dose- and time-dependent growth inhibition was observed in HeLa cells with an IC50 of approximately 10 mM at 24 h. DNA flow cytometric analysis indicated that 10 mM VPA induced a G2/M phase arrest of the cell cycle. This agent also induced apoptosis, which was accompanied by the cleavage of PARP, the activation of caspase-3, -8 and -9, and the loss of mitochondrial membrane potential (MMP; ??m). All the tested caspase inhibitors significantly prevented HeLa apoptotic cell death induced by VPA, whereas TNF-? intensified the apoptotic cell death. With respect to ROS and GSH levels, VPA increased ROS levels and induced GSH depletion. However, N-acetyl cysteine (NAC; an antioxidant) and L-buthionine sulfoximine (BSO; a GSH synthesis inhibitor) did not significantly affect cell death in VPA-treated HeLa cells. In conclusion, VPA inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis and the growth inhibition is independent of ROS and GSH level changes. PMID:24064712

Han, Bo Ram; You, Bo Ra; Park, Woo Hyun

2013-09-20

66

Melatonin Inhibition of Cancer Growth in Vivo Involves Suppression of Tumor Fatty Acid Metabolism via Melatonin Receptor-mediated Signal Transduction Events1  

Microsoft Academic Search

The growth of rat hepatoma 7288CTC in vivo is stimulated by the uptake of linoleic acid (LA) and its metabolism to 13-hydroxyoctadecadi- enoic acid (13-HODE), an important mitogenic signaling molecule within this tumor. Conversely, the growth of a variety of experimental cancers in vivo is inhibited by either physiological or pharmacological levels of the pineal gland hormone melatonin, although the

David E. Blask; Leonard A. Sauer; Robert T. Dauchy; Eugene W. Holowachuk; Mary S. Ruhoff; Heather S. Kopff

67

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

PubMed

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

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

2013-09-01

68

Correlation of Retinoid Binding Affinity to Retinoic Acid Receptor ot with Retinoid Inhibition of Growth of Estrogen Receptor-positive MCF7 Mammary Carcinoma Cells1  

Microsoft Academic Search

Both anchorage-dependent growth and anchorage-independent growth of the estrogen receptor-positive mammary carcinoma cell line MCF-7 are inhibited by all-ira\\/iv-retinoic acid. This cell line has nuclear retinole acid receptors (RARs) a and y. The natural retinoids all-acid and 9-cis-retinoic acid and a series of 12 conformationally restricted retinoids, which showed a range of binding selectivities for these receptors and had

Marcia I. Dawson; Wan-ru Chao; Polly Pine; Ling Jong; Peter D. Hobbs; Colette K. Rudd; Timothy C. Quick; Richard M. Niles; Xiao-kun Zhang; Angela Lombardo; Kathryn R. Ely; Braham Shroot; Joseph A. Fontana

69

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

PubMed Central

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

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

2011-01-01

70

Omega-3 Fatty Acids Inhibit Tumor Growth in a Rat Model of Bladder Cancer  

PubMed Central

Omega-3 (?-3) fatty acids have been tested on prevention and treatment of several cancer types, but the efficacy on “in vivo” bladder cancer has not been analyzed yet. This study aimed at evaluating the chemopreventive efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) mixture in an animal model of bladder cancer. Forty-four male Wistar rats were divided into 4 groups during a 20-week protocol: control; carcinogen—N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN); ?-3 (DHA + EPA); and ?-3 + BBN. BBN and ?-3 were given during the initial 8 weeks. At week 20 blood and bladder were collected and checked for the presence of urothelium lesions and tumors, markers of inflammation, proliferation, and redox status. Incidence of bladder carcinoma was, control (0%), ?-3 (0%), BBN (65%), and ?-3 + BBN (62.5%). The ?-3 + BBN group had no infiltrative tumors or carcinoma in situ, and tumor volume was significantly reduced compared to the BBN (0.9 ± 0.1?mm3 versus 112.5 ± 6.4?mm3). Also, it showed a reduced MDA/TAS ratio and BBN-induced serum CRP, TGF-?1, and CD31 were prevented. In conclusion, omega-3 fatty acids inhibit the development of premalignant and malignant lesions in a rat model of bladder cancer, which might be due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties.

Parada, Belmiro; Reis, Flavio; Cerejo, Raquel; Garrido, Patricia; Sereno, Jose; Xavier-Cunha, Maria; Neto, Paula; Mota, Alfredo; Figueiredo, Arnaldo; Teixeira, Frederico

2013-01-01

71

Hepatitis C virus Core protein overcomes all-trans retinoic acid-induced cell growth arrest by inhibiting retinoic acid receptor-?2 expression via DNA methylation.  

PubMed

Aberrant promoter methylation of tumor suppressor genes including retinoic acid receptor-?2 (RAR-?2) is frequently detected in hepatitis C virus (HCV)-associated hepatocellular carcinoma; however, the mechanism and its significance are relatively unknown. Here, we showed that HCV Core induced promoter hypermethylation of RAR-?2 to inhibit its expression via up-regulation of DNA methyltransferases 1 and 3b. Under the condition, all-trans retinoic acid (ATRA) failed to activate p16 expression and thus could not inactivate the Rb-E2F pathway. Accordingly, Core-expressing cells exhibited resistance to ATRA-induced growth inhibition. Taken together, HCV Core antagonizes ATRA, a natural anti-cancer compound, to stimulate cell growth via epigenetic down-regulation of RAR-?2. PMID:23474497

Lee, Hyehyeon; Woo, Young-Ju; Kim, Soo Shin; Kim, Sung-Hyun; Park, Bum-Joon; Choi, Dongho; Jang, Kyung Lib

2013-03-06

72

NAHA, a Novel Hydroxamic Acid-Derivative, Inhibits Growth and Angiogenesis of Breast Cancer In Vitro and In Vivo  

PubMed Central

Background We have recently synthesized novel N-alkylated amino acid-derived hydroxamate, 2-[Benzyl-(2-nitro-benzenesulfonyl)-amino]-N-hydroxy-3-methyl-N-propyl-butyramide (NAHA). Here, we evaluate the anticancer activity of NAHA against highly invasive human breast cancer cells MDA-MB-231 in vitro and in vivo. Methodology/Principal Findings Cell growth was evaluated by MTT and soft agar assays. Protein expression was determined by DNA microarray and Western blot analysis. Metastatic potential was evaluated by cell adhesion, migration, invasion, capillary morphogenesis, and ELISA assays. The anticancer activity in vivo was evaluated in mouse xenograft model. NAHA inhibited proliferation and colony formation of MDA-MB-231 cells together with the down-regulation of expression of Cdk2 and CDC20 proteins. NAHA inhibited cell adhesion, migration, and invasion through the suppression of secretion of uPA. NAHA suppressed secretion of VEGF from MDA-MB-231 cells and inhibited capillary morphogenesis of human aortic endothelial cells (HAECs). Finally, NAHA at 50 mg/kg was not toxic and decreased tumor volume and tumor weight in vivo. This suppression of tumor growth was associated with the inhibition of mitotic figures and induction of apoptosis, and the reduction of CD31 and VEGF positive cells in tumors. Conclusion NAHA could be a novel promising compound for the development of new drugs for the therapy of invasive breast cancers.

Jiang, Jiahua; Thyagarajan-Sahu, Anita; Krchnak, Viktor; Jedinak, Andrej; Sandusky, George E.; Sliva, Daniel

2012-01-01

73

Efficacy of organic acids, bacteriocins, and the lactoperoxidase system in inhibiting the growth of Cronobacter spp. in rehydrated infant formula.  

PubMed

Thirty-three antimicrobial agents, including antimicrobial peptides (nisin, lacticin 3147, isracidin), organic acids, emulsifiers (organic acid esters), glycine, lysozyme, tocopherol, EDTA, milk fat globule membrane, and the lactoperoxidase system (LPOS) were screened for anti-Cronobacter sakazakii activity. The compounds were initially screened individually in parallel in synthetic media. Those showing antimicrobial activity were then tested in reconstituted whole milk and finally in reconstituted powdered infant formula (PIF), using mild temperatures of reconstitution and prolonged storage at room temperature. Propionic acid and monocaprylin (as POEM M-100) in combination showed inhibitory activity at sufficiently low concentrations (0.1 to 0.2%) in milk to be considered as potential antimicrobial additives for the inhibition of C. sakazakii in reconstituted PIF. More interestingly, LPOS, when combined with the broad-spectrum bacteriocins nisin or lacticin 3147, inhibited outgrowth of C. sakazakii at 37°C for 8 h. The combined effects of POEM M-100 and either acetate or propionate and LPOS with lacticin 3147 or nisin were evaluated under the Food and Agriculture Organization of the United Nations-World Health Organization high-risk scenario for PIF, i.e., low temperature of reconstitution and long storage or feeding times at ambient temperature. In the presence of LPOS and lacticin 3147, growth of Cronobacter spp. was inhibited for up to 12 h when the PIF was rehydrated at 40 or 50°C. These results highlight the potential of combinatory approaches to improving the safety of infant milk formula. PMID:23043820

Oshima, Satoru; Rea, Mary C; Lothe, Sheba; Morgan, Sheila; Begley, Maire; O'Connor, Paula M; Fitzsimmons, Aidan; Kamikado, Hideaki; Walton, Richard; Ross, R Paul; Hill, Colin

2012-10-01

74

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

Microsoft Academic Search

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

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

1984-01-01

75

Endophytic Bacteria Improve Seedling Growth of Sunflower Under Water Stress, Produce Salicylic Acid, and Inhibit Growth of Pathogenic Fungi  

Microsoft Academic Search

Endophytic bacterial strains SF2 (99.9% homology with Achromobacter xylosoxidans), and SF3 and SF4 (99.9% homology with Bacillus pumilus) isolated from sunflower grown under irrigation or drought were selected on the basis of plant growth-promoting bacteria\\u000a (PGPB) characteristics. Aims of the study were to examine effects of inoculation with SF2, SF3, and SF4 on sunflower cultivated\\u000a under water stress, to evaluate salicylic acid

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

2010-01-01

76

Cerulenin-Inhibited Cells of Staphylococcus aureus Resume Growth When Supplemented with Either a Saturated or an Unsaturated Fatty Acid  

PubMed Central

In the presence of an inhibitory concentration of cerulenin, cells of Staphylococcus aureus can resume growth when supplemented with either a saturated or an unsaturated fatty acid. A requirement for both types of acids for growth could not be demonstrated.

Altenbern, Robert A.

1977-01-01

77

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

PubMed

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

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

2009-06-30

78

Retinol Inhibits the Growth of All-Trans-Retinoic Acid-Sensitive and All-Trans-Retinoic Acid-Resistant Colon Cancer Cells through a Retinoic Acid Receptor-Independent Mechanism  

Microsoft Academic Search

Retinol (vitamin A) is thought to exert its effects through the actions of its metabolite, all-trans-retinoic acid (ATRA), on gene transcription mediated by retinoic acid receptors (RAR) and retinoic acid response elements (RARE). However, retinoic acid resistance limits the chemotherapeutic potential of ATRA. We examined the ability of retinol to inhibit the growth of ATRA-sensitive (HCT-15) and ATRA-resistant (HCT-116, SW620,

Eun Young Park; Alice Dillard; Elizabeth A. Williams; Erik T. Wilder; M. Reese Pepper

2005-01-01

79

Nordihydroguaiaretic acid inhibits growth of cervical cancer SiHa cells by up-regulating p21  

PubMed Central

Nordihydroguaiaretic acid (NDGA) and its derivatives possess anti-cancer effects on various types of cancer via the induction of apoptosis or cell cycle arrest. This study proved that NDGA inhibited cervical cancer SiHa cell growth and induced cell cycle arrest at the G1 phase, which may be a consequence of cell cycle kinase inhibitor p21 induction. NDGA promoted acetylation of histone H3 in total and p21 gene-associated chromatin. This effect is gene selective, since NDGA has no impact on the p27 gene. NDGA also inhibited HPV-16 E6 gene transcription, which in turn resulted in the restoration of p53 protein levels. The silencing mediator for retinoid and thyroid hormone receptors (SMRT) is a key component of the HDAC3-HDAC4-N-CoR/SMRT complex. We found that NDGA significantly inhibited the transcription of SMRT, which, together with p53, may aid in the detection of the increase of histone H3 acetylation within the p21 gene. Our results suggest that NDGA induces p21 transcription by selectively elevating histone H3 acetylation associated with p21 gene and p53 protein levels via the inhibition of HPV-16 E6 expression.

GAO, PENG; ZHAI, FEI; GUAN, LEI; ZHENG, JIE

2011-01-01

80

Effect of organic acid and salt mixture on shelf-life extension and growth inhibition of Staphylococcus aureus and Escherichia coli O157:H7 in moo yor  

Microsoft Academic Search

This research investigated the effects of organic acids and salts solution on shelf-life extension and growth inhibition of Staphylococcus aureus and Escherichia coli O157:H7 in moo yor (pork bologna). A mixture of lactic acid, acetic acid, citric acid and their sodium salts was added to moo yor at various concentrations of 0 (control), 0.5, 0.75 and 1% (w\\/v) then stored

Puntarika Ratanatriwong; Preyatudsaney Prachaiyo; Pisit Wongsa-Ngasri

81

Usnic acid inhibits growth and induces cell cycle arrest and apoptosis in human lung carcinoma A549 cells.  

PubMed

Usnic acid (UA) is a secondary metabolite abundantly found in lichens. Some studies have shown the anticancer potential of UA; however, its efficacy and associated mechanisms are yet to be fully explored. Herein, we assessed the anticancer potency and associated molecular alterations by UA in human lung carcinoma A549 cells. UA treatment (25-100 ?M) for 24 and 48 h decreased total cell number by 39-67% (P < 0.01) and 68-89% (P < 0.001), respectively, and enhanced cell death by up to twofold and eightfold (P < 0.001), respectively. UA (1-10 ?M) also significantly (P < 0.001) suppressed colony formation of A549 cells. The cell growth inhibition was associated with cell cycle arrest at G0/ G1 phase. UA decreased the expression of cyclin-dependent kinase (CDK)4, CDK6, and cyclin D1 and increased the expression of CDK inhibitor (CDKI) p21/cip1 protein. While examining the cell death associated molecular changes, we observed that UA induces mitochondrial membrane depolarization and led to more than twofold increase (P < 0.01) in apoptotic cells. The apoptotic effect of UA was accompanied by enhanced poly(ADP-ribose) polymerase cleavage. This study shows that UA inhibits cell growth involving G0/G1 phase cell cycle arrest and induces cell death via mitochondrial membrane depolarization and induction of apoptosis in human lung carcinoma cells. PMID:23682781

Singh, Narendra; Nambiar, Dhanya; Kale, Raosaheb K; Singh, Rana P

2013-01-01

82

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

PubMed

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

Tsukahara, Tamotsu; Murakami-Murofushi, Kimiko

2012-09-24

83

Release of Cyclic Phosphatidic Acid from Gelatin-based Hydrogels Inhibit Colon Cancer Cell Growth and Migration  

PubMed Central

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.

Tsukahara, Tamotsu; Murakami-Murofushi, Kimiko

2012-01-01

84

Downregulation of L-type amino acid transporter 1 expression inhibits the growth, migration and invasion of gastric cancer cells  

PubMed Central

Gastric cancer is the second leading cause of cancer-related mortality worldwide. Identifying the molecules that play critical roles in the development of gastric cancer, and clarifying their mechanisms, will contribute to the development of novel molecularly targeted therapeutic drugs. Recently, the large (L)-type amino acid transporter 1 (LAT1), a glycoprotein that transports amino acids through the cell membrane when associated with CD98hc, has been demonstrated to be overexpressed in various types of cancer, and to regulate multiple biological process, including cell growth, migration and invasion. However, the involvement of LAT1 in gastric cancer remains unclear. In the present study, stable gastric cancer cell lines with a LAT1 knockdown were established by transfection of constructs with inserted short (sh) RNAs, in order to clarify the role of LAT1 in gastric caner. A significant decrease in LAT1 expression was observed in the established LAT1-silenced SGC7901 cells compared with the corresponding control cells; however, the expression levels of its partner, CD98hc, were not altered. Furthermore, downregulation of LAT1 expression inhibited the proliferation, migration and invasion of gastric cancer cells. In addition, the decreased expression of LAT1 induced cell cycle arrest in the G1/M phase. These findings suggested that LAT1 may be significant in the progression and metastasis of gastric cancer, and may be developed as a therapeutic target for cancer therapy.

SHI, LIANGHUI; LUO, WENPING; HUANG, WENBING; HUANG, SHISUI; HUANG, GUANGYAN

2013-01-01

85

Growth-inhibition of hiochi bacteria in namazake (raw sake) by bacteriocins from lactic acid bacteria  

Microsoft Academic Search

The bacteriocins produced by Lactococcus lactis subsp. lactis C101910 (C101910) and NBRC 12007 (NBRC 12007) were used to prevent the growth of sake spoiling hiochi bacteria (Lactobacillus hilgardii, Lactobacillus fructivorans, and Lactobacillus paracasei) in namazake, which is raw (unpasteurized) sake. The bacteriocin concentrations required for decreasing the viable cell concentrations of L. hilgardii and L. fructivorans below the detection limit

Masayuki Taniguchi; Yohei Ishiyama; Takeomi Takata; Toshihiro Nakanishi; Mitsuoki Kaneoke; Ken-ichi Watanabe; Fujitoshi Yanagida; Yi-sheng Chen; Tomoaki Kouya; Takaaki Tanaka

2010-01-01

86

Growth inhibition and apoptotic effect of alpha-eleostearic acid on human breast cancer cells  

Microsoft Academic Search

Alpha-eleostearic acid (?-ESA) is a natural and biologically active compound which possesses potent antioxidant and anti-tumor\\u000a activity. The purpose of this study was to confirm the anticancer activity of ?-ESA against human breast cancer cells and\\u000a to further elucidate its mechanism of activity. Human breast cancer cells and normal liver cells were used for in-vitro tests\\u000a of the anticancer activity

Tingting ZhangYanping; Yanping Gao; Yu Mao; Quanbo Zhang; Caiyu Lin; Ping Lin; Jie Zhang; Xiujie Wang

87

Inhibition of the growth of mammalian cells in culture by amino acids and the isolation and characterization of L -phenylalanine-resistant mutants modifying L -phenylalanine transport  

Microsoft Academic Search

Raising the concentration of phenylalanine and other amino acids in MEM leads to the inhibition of growth and in some cases to death of A9, Balb 3T3, SV40 Balb 3T3 (SVT2), CHO, and WI38. All cells tested exhibited some similar sensitivities to certain of the amino acids, but there were some unique differences. Phenylalanine-resistant mutants (Phe\\u000a\\u000ar\\u000a)of A9 were

Ellis Englesberg; Richard Bass; William Heiser

1976-01-01

88

Lactate Acid Inhibition of Salmonella Typhimurium in Yogurt  

Microsoft Academic Search

We determined how lactic acid inhibits growth of Salmonella typhimurium in yogurt. This inhibition was demonstrated by microscopic examination not to be due to bacteriolysis. Neither growth nor meta- bolic activity could be initiated after cells were washed in phosphate buffer and exposed to 1.5% lactic acid for 1 h at 3 7°C, indicating that lactic acid inhibition is irreversible.

Howard E. Rubin; Thomas Nerad; Frizell Vaughan

1982-01-01

89

Polymalic acid nanobioconjugate for simultaneous immunostimulation and inhibition of tumor growth in HER2/neu-positive breast cancer.  

PubMed

Breast cancer remains the second leading cause of cancer death among women in the United States. Breast cancer prognosis is particularly poor in case of tumors overexpressing the oncoprotein HER2/neu. A new nanobioconjugate of the Polycefin(TM) family of anti-cancer drugs based on biodegradable and non-toxic polymalic acid (PMLA) was engineered for a multi-pronged attack on HER2/neu-positive breast cancer cells. An antibody-cytokine fusion protein consisting of the immunostimulatory cytokine interleukin-2 (IL-2) genetically fused to an antibody specific for human HER2/neu [anti-HER2/neu IgG3-(IL-2)] was covalently attached to the PMLA backbone to target HER2/neu expressing tumors and ensure the delivery of IL-2 to the tumor microenvironment. Antisense oligonucleotides (AON) were conjugated to the nanodrug to inhibit the expression of vascular tumor protein laminin-411 in order to block tumor angiogenesis. It is shown that the nanobioconjugate was capable of specifically binding human HER2/neu and retained the biological activity of IL-2. We also showed the uptake of the nanobioconjugate into HER2/neu-positive breast cancer cells and enhanced tumor targeting in vivo. The nanobioconjugate exhibited marked anti-tumor activity manifested by significantly longer animal survival and significantly increased anti-HER2/neu immune response in immunocompetent mice bearing D2F2/E2 murine mammary tumors that express human HER2/neu. The combination of laminin-411 AON and antibody-cytokine fusion protein on a single polymeric platform results in a new nanobioconjugate that can act against cancer cells through inhibition of tumor growth and angiogenesis and the orchestration of an immune response against the tumor. The present Polycefin(TM) variant may be a promising agent for treating HER2/neu expressing tumors and demonstrates the versatility of the Polycefin(TM) nanobioconjugate platform. PMID:23770212

Ding, Hui; Helguera, Gustavo; Rodríguez, José A; Markman, Janet; Luria-Pérez, Rosendo; Gangalum, Pallavi; Portilla-Arias, Jose; Inoue, Satoshi; Daniels-Wells, Tracy R; Black, Keith; Holler, Eggehard; Penichet, Manuel L; Ljubimova, Julia Y

2013-06-12

90

Locked nucleic acid modified DNA enzymes targeting early growth response-1 inhibit human vascular smooth muscle cell growth  

Microsoft Academic Search

Smooth muscle cell (SMC) proliferation and migration are key processes that occur in the pathogenesis of atherosclerosis and post-angio- plasty restenosis. In the present study, we designed locked nucleic acid (LNA)-modified DNAzymes targeting a specific region spanning the transla- tional start site of human EGR-1, an immediate-early gene, wherein two of the nucleotides in each of the 9+9 hybridizing arms

Roger G. Fahmy; Levon M. Khachigian

2004-01-01

91

Retinoid metabolism and all-trans retinoic acid-induced growth inhibition in head and neck squamous cell carcinoma cell lines.  

PubMed Central

Retinoids can reverse potentially premalignant lesions and prevent second primary tumours in patients with head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been reported that acquired resistance to all-trans retinoic acid (RA) in leukaemia is associated with decreased plasma peak levels, probably the result of enhanced retinoid metabolism. The aim of this study was to investigate the metabolism of retinoids and relate this to growth inhibition in HNSCC. Three HNSCC cell lines were selected on the basis of a large variation in the all-trans RA-induced growth inhibition. Cells were exposed to 9.5 nM (radioactive) for 4 and 24 h, and to 1 and 10 microM (nonradioactive) all-trans RA for 4, 24, 48 and 72 h, and medium and cells were analysed for retinoid metabolites. At all concentrations studied, the amount of growth inhibition was proportional to the extent at which all-trans-, 13- and 9-cis RA disappeared from the medium as well as from the cells. This turnover process coincided with the formation of a group of as yet unidentified polar retinoid metabolites. The level of mRNA of cellular RA-binding protein II (CRABP-II), involved in retinoid homeostasis, was inversely proportional to growth inhibition. These findings indicate that for HNSCC retinoid metabolism may be associated with growth inhibition. Images Figure 6

Braakhuis, B. J.; Klaassen, I.; van der Leede, B. M.; Cloos, J.; Brakenhoff, R. H.; Copper, M. P.; Teerlink, T.; Hendriks, H. F.; van der Saag, P. T.; Snow, G. B.

1997-01-01

92

The retinoic acid receptor antagonist, BMS453, inhibits normal breast cell growth by inducing active TGFbeta and causing cell cycle arrest.  

PubMed

We have previously shown that a retinoic acid receptor (RAR) antagonist BMS453, which does not activate RAR-dependent gene transcription in breast cells, inhibits normal breast cell growth. In this study we have investigated the mechanisms by which this retinoid receptor antagonist inhibits cell growth. Both all trans retinoic acid (atRA) and BMS453 inhibited the proliferation of normal breast cell growth without significantly inducing apoptosis. Both retinoids caused a G1 block in the cell cycle with an increase in the proportion of cells in G0/G1 and a decrease in the proportion of cells in S phase. We then investigated the effects of the retinoids on molecules that regulate the G1 to S transition. These studies demonstrated that both atRA and BMS453 induce Rb hypophosphorylation and decrease CDK2 kinase activity. We then studied the effect of the retinoids on the expression of CDK inhibitors. atRA and BMS453 increased total p21 protein levels and CDK2-bound p21 protein, but did not change CDK4-bound p21. These results suggest that atRA and BMS453 increase p21, decrease CDK2 kinase activity, which in turn leads to hypophosphorylation of Rb and G1 arrest. Because transforming growth factor beta (TGFbeta) has been proposed as a mediator of retinoid-induced growth inhibition, we next investigated whether TGFbeta mediates the anti-proliferative effect of atRA and BMS453 in normal breast cells. These studies showed that atRA and BMS453 increased total TGFbeta activity by 3-5-fold. However, BMS453 increased active TGFbeta activity by 33-fold while atRA increased active TGFbeta activity by only threefold. These results suggest that BMS453 treatment induces conversion of latent TGFbeta to active TGFbeta. To investigate whether this increase in active TGFbeta mediates the anti-proliferative effects of these retinoids, a TGFbeta-blocking antibody was used in an attempt to prevent retinoid-induced growth inhibition. Results from these experiments showed that the anti-TGFbeta antibody prevented the inhibition of cell proliferation induced by BMS453, but did not prevent the inhibition of cell proliferation induced by atRA. These results demonstrate that BMS453 inhibits breast cell growth predominantly through the induction of active TGFbeta, while atRA inhibits growth through other mechanisms. These results suggest that retinoid analogs that increase active TGFbeta may be promising agents for the prevention of breast cancer. PMID:11753686

Yang, L; Ostrowski, J; Reczek, P; Brown, P

2001-11-29

93

Stimulation with inhibited acidizing fluids  

Microsoft Academic Search

Production and injection wells are stimulated with an inhibited acidizing microemulsion containing hydrocarbon (external phase), surfactant, and acid. The acid is inhibited from reacting with the reservoir rock until it has penetrated the rock face. About 5 to 500 gal of the microemulsion per vertical foot of formation are useful to stimulate the wells. Carbonate reservoirs are particulary suited for

C. T. Presley; R. E. Smith

1974-01-01

94

Nucleic acids potentiate Factor VII-activating protease (FSAP)-mediated cleavage of platelet-derived growth factor-BB and inhibition of vascular smooth muscle cell proliferation  

PubMed Central

FSAP (Factor VII-activating protease) can cleave and inactivate PDGF-BB (platelet-derived growth factor-BB) and thereby inhibits VSMC (vascular smooth-muscle cell) proliferation. The auto-activation of FSAP is facilitated by negatively charged polyanions such as heparin, dextransulfate or extracellular ribonucleic acids. Since auto-activation is essential for the anti-proliferative function of FSAP, the influence of nucleic acids as cofactors for the FSAP-mediated inhibition of PDGF-BB was investigated. Natural or artificial RNA was an effective cofactor for FSAP mediated PDGF-BB degradation, whereas the effect of DNA was weak. RNA-induced cleavage of PDGF-BB was inhibited by serine protease inhibitors. The pattern of PDGF-BB cleavage was identical with either heparin or RNA as a cofactor. One of the cleavage sites in PDGF-BB was at the positions 160–162 (R160KK162), which is an important region for receptor binding and activation. In VSMCs, PDGF-BB-stimulated DNA synthesis was inhibited by FSAP in the presence of RNA. RNA was more effective than DNA and the cofactor activity of RNA was neutralized after pretreatment with RNase. FSAP binding to RNA protected the nucleic acid from degradation by RNase. These data are relevant to situations where extracellular nucleic acids released from necrotic or apoptotic cells could activate local FSAP, leading to inhibition of PDGF-BB.

Shibamiya, Aya; Muhl, Lars; Tannert-Otto, Susanne; Preissner, Klaus T.; Kanse, Sandip M.

2007-01-01

95

Nordihydroguaiaretic Acid (NDGA) Inhibits the IGF-1 and c-erbB2\\/HER2\\/neu Receptors and Suppresses Growth in Breast Cancer Cells  

Microsoft Academic Search

Summary  Nordihydroguaiaretic acid (NDGA) is a phenolic compound isolated from the creosote bush Larrea divaricatta that has anti-cancer activities both in vitro and in vivo. We can now attribute certain of these anti-cancer properties in breast cancer cells to the ability of NDGA to directly inhibit\\u000a the function of two receptor tyrosine kinases (RTKs), the insulin-like growth factor receptor (IGF-1R) and

Jack F. Youngren; Karissa Gable; Cristina Penaranda; Betty A. Maddux; Marianna Zavodovskaya; Margaret Lobo; Michael Campbell; John Kerner; Ira D. Goldfine

2005-01-01

96

RRIG1 Mediates Effects of Retinoic Acid Receptor B2 on Tumor Cell Growth and Gene Expression through Binding to and Inhibition of RhoA  

Microsoft Academic Search

The expression of retinoic acid receptor B2 (RAR-B2 )i s frequently lost in various cancers and their premalignant lesions. However,the restoration of RAR- B2 expression inhibits tumor cell growth and suppresses cancer development. To understand the molecular mechanisms responsible for this RAR-B2-mediated antitumor activity,we did restriction frag- ment differential display-PCR and cloned a novel retinoid receptor-induced gene 1 (RRIG1),which is

Zheng D. Liang; Scott M. Lippman; Tsung-Teh Wu; Reuben Lotan; Xiao-Chun Xu

2006-01-01

97

Thyroid autoregulation. Inhibition of goiter growth and of cyclic AMP formation in rat thyroid by iodinated derivatives of arachidonic acid.  

PubMed

Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompund. Data from different laboratories have shown that the thyroid is capable of producing different iodolipids, including iodinated derivatives of arachidonic acid; such as 5-hydroxy-6-iodo-8, 11, 14-eicosatrienoic-delta-lactone (IL-delta). Previous results from our laboratory showed that a semi-purified preparation of iodinated arachidonic acid exerts an inhibitory action in vitro on calf thyroid. In the present studies three purified iodinated derivatives of arachidonic acid were synthesized: IL-delta; 14-iodo-15-hydroxy-5, 8, 11-eicosatrienoic acid (I-OH-A) and its corresponding omega-lactone (IL-omega). Their action on MMI-induced goiter was studied in rats. Administration of MMI to rats during 10 days increased thyroid weight by 124%. This effect was significantly inhibited by the simultaneous injection of 5 micrograms/day of I-OH-A (57% inhibition of MMI action), IL-W (39%), IL-delta (33%) and T3 (95%), while arachidonic acid was without action. No inhibition was found with 1.25 micrograms/day Kl, a dose equivalent to that which could be originated from total dehalogenation of the iodocompounds. These results support the idea that these iodocompounds have an intrinsic biologic activity and that there is a correlation between action and chemical structure. Serum TSH was increased around 15-20 fold after MMI administration. Chronic or acute injection of I-OH-A failed to alter TSH levels, indicating that this iodocompound exerts its action directly on the gland, without altering TSH concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2851622

Pisarev, M A; Chazenbalk, G D; Valsecchi, R M; Burton, G; Krawiec, L; Monteagudo, E; Juvenal, G J; Boado, R J; Chester, H A

1988-10-01

98

AtrbohD and AtrbohF positively regulate abscisic acid-inhibited primary root growth by affecting Ca2+ signalling and auxin response of roots in Arabidopsis.  

PubMed

Reactive oxygen species (ROS) originating from the NADPH oxidases AtrbohD and AtrbohF play an important role in abscisic acid (ABA)-inhibited primary root growth in Arabidopsis. However, the mechanisms underlying this process remain elusive. In this study, the double mutant atrbohD1/F1 and atrbohD2/F2, in which both AtrbohD and AtrbohF were disrupted, were less sensitive to ABA suppression of root cell elongation than wild-type (WT) plants. Furthermore, the double mutants showed impaired ABA responses in roots, including ROS generation, cytosolic Ca(2+) increases, and activation of plasma membrane Ca(2+)-permeable channels compared with WT. Exogenous H2O2 can activate the Ca(2+) currents in roots of atrbohD1/F1. In addition, exogenous application of the auxin transport inhibitor naphthylphthalamic acid effectively promoted ABA inhibition of root growth of the mutants relative to that of WT. The ABA-induced decreases in auxin sensitivity of the root tips were more pronounced in WT than in atrbohD1/F1. These findings suggest that both AtrbohD and AtrbohF are essential for ABA-promoted ROS production in roots. ROS activate Ca(2+) signalling and reduce auxin sensitivity of roots, thus positively regulating ABA-inhibited primary root growth in Arabidopsis. PMID:23963673

Jiao, Yiheng; Sun, Lirong; Song, Yalin; Wang, Limin; Liu, Liping; Zhang, Liyue; Liu, Bo; Li, Ning; Miao, Chen; Hao, Fushun

2013-08-20

99

Inhibition of trans-Retinoic Acid-Resistant Human Breast Cancer Cell Growth by Retinoid X Receptor-Selective Retinoids  

Microsoft Academic Search

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 RARa and RARb. In this study, we evaluated several

QIAO WU; MARCIA I. DAWSON; YUN ZHENG; PETER D. HOBBS; ANISSA AGADIR; LING JONG; YIN LI; RU LIU; BINGZHEN LIN; XIAO-KUN ZHANG

1997-01-01

100

Suppression of interleukin 2-dependent human T cell growth in vitro by prostaglandin E (PGE) and their precursor fatty acids. Evidence for a PGE-independent mechanism of inhibition by the fatty acids.  

PubMed Central

PGE represent oxygenation products of polyunsaturated essential fatty acids and are important regulators of cell-mediated immune responses. Because oils enriched in such fatty acids reduce inflammation and tissue injury in vivo, we examined the effects of these PGE precursors on IL-2-driven growth of human T lymphocytes. Dihomogamma linoleic acid (DGLA), AA, and their metabolites (PGE1 and PGE2, respectively) strongly inhibited short- and long-term growth of IL-2-dependent T cell cultures; EPA was much less inhibitory and its product, PGE3, failed to suppress IL-2 responses. Short-term pretreatment of the cells with DGLA or AA and removal of the fatty acids before the proliferation assay resulted in a smaller reduction in [3H]TdR incorporation. PGE and fatty acids did not alter the number of high affinity IL-2 binding sites on the T cell cultures but reduced the percentage of cells expressing CD25 and HLA class II molecules. No PGE was detected in supernatants from the fatty acid-treated cultures. Moreover, indomethacin, a cyclooxygenase inhibitor, did not reverse the antiproliferative effects of the fatty acids. Together, these findings indicate that fatty acids can inhibit IL-2-driven T cell growth via a PGE-independent mechanism and might be relevant to inflammatory diseases associated with persistent T cell activation. Images

Santoli, D; Phillips, P D; Colt, T L; Zurier, R B

1990-01-01

101

N-3 Poly-Unsaturated Fatty Acids Shift Estrogen Signaling to Inhibit Human Breast Cancer Cell Growth  

PubMed Central

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

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

2012-01-01

102

THE NSAID TOLFENAMIC ACID INHIBITS BT474 AND SKBR3 BREAST CANCER CELL AND TUMOR GROWTH BY REPRESSING erbB2 EXPRESSION  

PubMed Central

Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug that inhibits pancreatic cancer cell and tumor growth THROUGH decreasing expression of specificity protein (Sp) transcription factors. TA also inhibits growth of erbB2-overexpressing BT474 and SKBR3 breast cancer cells; however, in contrast to pancreatic cancer cells, TA induced downregulation of erbB2 but not Sp proteins. TA-induced erbB2 downregulation was accompanied by decreased erbB2-dependent kinase activities, induction of p27, and decreased expression of cyclin D1. TA also decreased erbB2 mRNA expression and promoter activity, and this was due to decreased mRNA stability in BT474 cells and, in both cell lines, TA decreased expression of the YY1 and AP-2 transcription factors required for basal erbB2 expression. In addition, TA also inhibited tumor growth in athymic nude mice in which BT474 cells were injected into the mammary fat pad. TA represents a novel and promising new anticancer drug that targets erbB2 by decreasing transcription of this oncogene.

Liu, Xinyi; Abdelrahim, Maen; Abudayyeh, Suhaib; Lei, Ping; Safe, Stephen

2009-01-01

103

Phosphanilic Acid Inhibits Dihydropteroate Synthase.  

National Technical Information Service (NTIS)

Intact cells of Pseudomonas aeruginosa were more susceptible to phosphanilic acid (PA) than cells of Escherichia coli. In cell extract, the dihydropteroate synthases of P. aeruginosa and E. coli were about equally susceptible to inhibition by PA. These re...

R. G. Eagon A. T. McManus

1989-01-01

104

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

PubMed

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

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

2013-10-30

105

Salvianolic Acid B Inhibits Growth of Head and Neck Squamous Cell Carcinoma in vitro and in vivo via Cyclooxygenase-2 and Apoptotic Pathways  

PubMed Central

Overexpression of cyclooxygenase-2 (COX-2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a non steroidal anti-inflammatory drug, which inhibits COX-2 but not COX-1. This selective COX-2 inhibitor holds promise as a cancer preventive agent. Concerns about cardiotoxicity of celecoxib, limits its use in long term chemoprevention and therapy. Salvianolic acid B (Sal-B) is a leading bioactive component of Salvia miltiorrhiza Bge, which is used for treating neoplastic and chronic inflammatory diseases in China. The purpose of this study was to investigate the mechanisms by which Sal-B inhibits HNSCC growth. Sal-B was isolated from Salvia miltiorrhiza Bge by solvent extraction followed by two chromatographic steps. Pharmacological activity of Sal-B was assessed in HNSCC and other cell lines by estimating COX-2 expression, cell viability and caspase-dependent apoptosis. Sal-B inhibited growth of HNSCC JHU-022 and JHU-013 cells with IC50 of 18 and 50 µM respectively. Nude mice with HNSCC solid tumor xenografts were treated with Sal-B (80mg/kg/day) or celecoxib (5mg/kg/day) for 25 days to investigate in vivo effects of the COX-2 inhibitors. Tumor volumes in Sal-B treated group were significantly lower than those in celecoxib treated or untreated control groups (p<0.05). Sal-B inhibited COX-2 expression in cultured HNSCC cells and in HNSCC cells isolated from tumor xenografts. Sal-B also caused dose-dependent inhibition of prostaglandin E2 synthesis, either with or without lipopolysaccharide stimulation. Taken together, Sal-B shows promise as a COX-2 targeted anticancer agent for HNSCC prevention and treatment.

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

2010-01-01

106

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

PubMed Central

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

2011-01-01

107

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

USGS Publications Warehouse

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

Sparling, D.W.

1990-01-01

108

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

PubMed Central

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

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

2011-01-01

109

The Pseudomonas aeruginosa toxin L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth and induces encystment in Acanthamoeba castellanii.  

PubMed

L-2-Amino-4-methoxy-trans-3-butenoic acid (AMB) is a toxic antimetabolite produced by the opportunistic pathogen Pseudomonas aeruginosa. To evaluate its importance as a potential virulence factor, we tested the host response towards AMB using an Acanthamoeba castellanii cell model. We found that AMB (at concentrations ? 0.5 mM) caused amoebal encystment in salt buffer, while inhibiting amoebal growth in rich medium in a dose-dependent manner. However, no difference in amoebal plaque formation was observed on bacterial lawns of wild type and AMB-negative P. aeruginosa strains. We thereby conclude that AMB may eventually act as a virulence factor, but only at relatively high concentrations. PMID:22064067

Lee, Xiaoyun; Reimmann, Cornelia; Greub, Gilbert; Sufrin, Janice; Croxatto, Antony

2011-10-24

110

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

PubMed

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. PMID:23831623

Wu, Pei-Yi; Lin, Yueh-Chien; Lan, Shun-Yan; Huang, Yuan-Li; Lee, Hsinyu

2013-07-03

111

High Concentrations of L-Ascorbic Acid Specifically Inhibit the Growth of Human Leukemic Cells via Downregulation of HIF-1? Transcription  

PubMed Central

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

Sawanobori, Masakazu; Uno, Tomoko; Matsuzawa, Hideyuki; Nakamura, Yoshihiko; Matsushita, Hiromichi; Ando, Kiyoshi

2013-01-01

112

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

Microsoft Academic Search

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

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

1992-01-01

113

Retinoic acid receptor ? mediates growth inhibition by retinoids in rat pancreatic carcinoma DSL6A\\/C1 cells  

Microsoft Academic Search

During carcinogenesis, pancreatic acinar cells can dedifferentiate into ductal adenocarcinoma of the pancreas. DSL-6A\\/C1 cells represent an in vitro model of this carcinogenic sequence. This study was designed to examine the effects of retinoids on cell growth in DSL-6A\\/C1 cells and to characterize further the molecular mechanisms underlying the antiproliferative actions of retinoids. Treatment of DSL-6A\\/C1 cells with retinoids results

FH Brembeck; A Kaiser; K Detjen; H Hotz; T Foitzik; HJ Buhr; E-O Riecken; S Rosewicz

1998-01-01

114

Transforming Growth Factor s Inhibit Somatostatin Messenger Ribonucleic Acid Levels and Somatostatin Secretion in Hypothalamic Cells in Culture  

Microsoft Academic Search

Treatment of hypothalamic cells in monolayer culture with trans- forming growth factor-b1 (TGFb1) significantly reduced both basal and cAMP-induced somatostatin messenger RNA (mRNA) levels and somatostatin secretion. This inhibitory effect was dose- and time- dependent and not mediated by glial cells, as it was also observed in glial-free hypothalamic cell cultures treated with cytosine arabino- nucleoside. TGFb2 and -b3 mimicked

M. Quintela; R. M. SENARÍS; C. DIEGUEZ

1997-01-01

115

The bisphosphonate zoledronic acid inhibits the growth of HCT116 colon carcinoma cells and induces tumor cell apoptosis  

Microsoft Academic Search

Besides its preventive action on bone resorption the third generation bisphosphonate zoledronic acid (ZOL) has been shown\\u000a to display potent inhibitory action on the formation of bone metastases of various human cancers. Recent research also indicates\\u000a an antitumoral effect on primary tumors and visceral metastases. Here we investigate for the first time the effect of ZOL\\u000a on the human colon

Lilian Sewing; Florian Steinberg; Harald Schmidt; Rüdiger Göke

2008-01-01

116

Tolfenamic Acid Induces Apoptosis and Growth Inhibition in Head and Neck Cancer: Involvement of NAG1 Expression  

Microsoft Academic Search

Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is induced by nonsteroidal anti-inflammatory drugs and possesses proapoptotic and antitumorigenic activities. Although tolfenamic acid (TA) induces apoptosis in head and neck cancer cells, the relationship between NAG-1 and TA has not been determined. This study investigated the induction of apoptosis in head and neck cancer cells treated by TA and the role of NAG-1

Sung Un Kang; Yoo Seob Shin; Hye Sook Hwang; Seung Joon Baek; Seong-Ho Lee; Chul-Ho Kim

2012-01-01

117

The 104 -123 Amino Acid Sequence of the b-domain of von Hippel-Lindau Gene Product Is Sufficient to Inhibit Renal Tumor Growth and Invasion1  

Microsoft Academic Search

The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in patients with VHL disease and in the majority of patients with sporadic renal cell carcinomas (RCCs). RCCs are dependent on insulin-like growth factor-I receptor-mediated signaling for tumor growth and invasion in vivo. Reintroduction of the VHL gene product (pVHL) can inhibit on insulin-like growth factor-I receptor-mediated signaling in RCC cells

Kaustubh Datta; Christian Sundberg; S. Ananth Karumanchi; Debabrata Mukhopadhyay

2001-01-01

118

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

SciTech Connect

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.

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

1990-08-01

119

The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth inhibition and enhances taxol-induced cell death in breast cancer  

Microsoft Academic Search

Purpose  The histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) enhances taxol-induced antitumor effects\\u000a against some human cancer cells. The aim of this study is to investigate whether SAHA can enhance taxol-induced cell death\\u000a against human breast cancer cells and to illustrate the mechanism in detail.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A panel of eight human breast cancer cell lines and an immortalized human breast epithelial

Yi-kang Shi; Zhong-hua Li; Xi-qian Han; Ji-hu Yi; Zhen-hua Wang; Jing-li Hou; Cong-ran Feng; Qing-hong Fang; Hui-hui Wang; Peng-fei Zhang; Feng-shan Wang; Jie Shen; Peng Wang

2010-01-01

120

All-trans retinoic acid converts E2F into a transcriptional suppressor and inhibits the growth of normal human bronchial epithelial cells through a retinoic acid receptor- dependent signaling pathway.  

PubMed Central

Retinoids, including retinol and retinoic acid derivatives, maintain the normal growth and differentiation of human bronchial epithelial (HBE) cells and are under investigation as agents for lung cancer prevention. In this study, we examined the biologic effects of retinoids on normal HBE cells and the molecular mechanisms of retinoid actions. At a dose of 10(-6) M, all-trans retinoic acid (t-RA) suppressed the proliferation of normal HBE cells, which accumulated in the G0 phase. No evidence of programmed cell death was observed. The class of retinoid nuclear receptor that mediated the growth arrest was explored. Normal HBE cell growth was suppressed by a retinoid that selectively activates retinoic acid receptors but not by one that activates retinoid X receptors. The E2F transcription factor has demonstrated a role in G0 entry through transcriptional suppression of genes that induce cell cycle progression. To investigate the role of E2F in retinoid signaling, transient transfection assays were performed using reporter plasmids containing E2F-binding sites. Findings from these experiments suggested that t-RA treatment converted E2F into a transcriptional suppressor. Supporting this possibility, t-RA inhibited the expression of the E2F target genes B-myb, cyclin A, and cyclin E. Further, t-RA increased the levels of nuclear E2F-4, p107, and p130 and enhanced the binding of E2F-4 to p107, which have been associated with the conversion of E2F into a transcriptional suppressor in other cells. These findings point to retinoic acid receptor- and E2F-dependent pathways as potential mediators of retinoid-induced growth arrest in normal HBE cells and have implications for the use of retinoids in clinical trials on the prevention of lung cancer.

Lee, H Y; Dohi, D F; Kim, Y H; Walsh, G L; Consoli, U; Andreeff, M; Dawson, M I; Hong, W K; Kurie, J M

1998-01-01

121

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

PubMed

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

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

2005-12-01

122

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

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

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

2012-10-08

123

Effect of epoxyeicosatrienoic acids on growth hormone release from somatotrophs.  

PubMed

Growth hormone secretion was stimulated in vitro by products of arachidonic acid epoxygenase, the epoxyeicosatrienoic acids. 5,6-Epoxyeicosatrienoic and 14,15-epoxyeicosatrienoic acid stimulated growth hormone release from an enriched population of somatotrophs (approximately 85%) by twofold. Inhibition of arachidonic acid metabolism by indomethacin did not affect growth hormone-releasing hormone stimulation of growth hormone release. In contrast, pretreatment of somatotrophs with an 11,12-isonitrile analogue of arachidonic acid that inhibits arachidonic acid epoxygenase, resulted in a 20-25% inhibition of growth hormone-releasing hormone-stimulated growth hormone release. 14,15-Epoxyeicosatrienoic acid stimulated a concentration-dependent increase (twofold) in the cytoplasmic concentration of adenosine 3',5'-cyclic monophosphate (cAMP) in the somatotrophs. 14,15-Epoxyeicosatrienoic acid also rapidly increased the intracellular free calcium concentration in somatotrophs from resting levels (approximately 80 nM) to greater than 250 nM. Growth hormone-releasing hormone increased the free intracellular calcium to 160-180 nM. Preincubation of somatotrophs with somatostatin inhibited growth hormone-releasing hormone-stimulated growth hormone secretion, cAMP accumulation, and 14,15-epoxyeicosatrienoic acid stimulated cAMP accumulation. These data are suggestive that the epoxyeicosatrienoic acids may have a role in the secretion of growth hormone. PMID:2563927

Snyder, G D; Yadagiri, P; Falck, J R

1989-02-01

124

Inhibition of Ethylene Biosynthesis by Salicylic Acid  

PubMed Central

Salicylic acid inhibited ethylene formation from ACC in self-buffered (pH 3.8) pear (Pyrus communis) cell suspension cultures with a K1app of about 10 micromolar after 1 to 3 hours incubation. Inhibition appeared noncompetitive. Among 22 related phenolic compounds tested, only acetylsalicylic acid showed similar levels of inhibition. Inhibition by salicylic acid was inversely dependent on the pH of the culture medium and did not require a continuous external supply of salicylate. When compared to known inhibitors of the ethylene forming enzyme, cobalt, n-propyl gallate, and dinitrophenol, inhibition by salicylic acid most closely resembled that by dinitrophenol but salicylic acid did not produce the same degree of respiratory stimulation. Results are discussed in terms of other known effects of salicylic acid on plants, pH-dependency, and the possible influence of salicylic acid on electron transport.

Leslie, Charles A.; Romani, Roger J.

1988-01-01

125

p38 MAPK activation, JNK inhibition, neoplastic growth inhibition, and increased gap junction communication in human lung carcinoma and Ras-transformed cells by 4-phenyl-3-butenoic acid.  

PubMed

Human lung neoplasms frequently express mutations that down-regulate expression of various tumor suppressor molecules, including mitogen-activated protein kinases such as p38 MAPK. Conversely, activation of p38 MAPK in tumor cells results in cancer cell cycle inhibition or apoptosis initiated by chemotherapeutic agents such as retinoids or cisplatin, and is therefore an attractive approach for experimental anti-tumor therapies. We now report that 4-phenyl-3-butenoic acid (PBA), an experimental compound that reverses the transformed phenotype at non-cytotoxic concentrations, activates p38 MAPK in tumorigenic cells at concentrations and treatment times that correlate with decreased cell growth and increased cell-cell communication. H2009 human lung carcinoma cells and ras-transformed rat liver epithelial cells treated with PBA showed increased activation of p38 MAPK and its downstream effectors which occurred after 4?h and lasted beyond 48?h. Untransformed plasmid control cells showed low activation of p38 MAPK compared to ras-transformed and H2009 carcinoma cells, which correlates with the reduced effect of PBA on untransformed cell growth. The p38 MAPK inhibitor, SB203580, negated PBA's activation of p38 MAPK downstream effectors. PBA also increased cell-cell communication and connexin 43 phosphorylation in ras-transformed cells, which were prevented by SB203580. In addition, PBA decreased activation of JNK, which is upregulated in many cancers. Taken together, these results suggest that PBA exerts its growth regulatory effect in tumorigenic cells by concomitant up-regulation of p38 MAPK activity, altered connexin 43 expression, and down-regulation of JNK activity. PBA may therefore be an effective therapeutic agent in human cancers that exhibit down-regulated p38 MAPK activity and/or activated JNK and altered cell-cell communication. PMID:21898549

Matesic, Diane F; Sidorova, Tatyana S; Burns, Timothy J; Bell, Allison M; Tran, Paul L; Ruch, Randall J; May, Sheldon W

2012-01-01

126

Inhibitors of the Arachidonic Acid Pathway and Peroxisome Proliferator-Activated Receptor Ligands Have Superadditive Effects on Lung Cancer Growth Inhibition  

Microsoft Academic Search

Arachidonic acid (AA) metabolizing enzymes and peroxisome proliferator-activated receptors (PPARs) have been shown to regulate the growth of epithelial cells. We have previously reported that exposure to the 5-lipoxygenase activating protein-directed inhibitor MK886 but not the cyclooxygenase inhibitor, indomethacin, reduced growth, increased apoptosis, and up-regulated PPARA and ; expression in breast cancer cell lines. In the present study, we explore

Ingalill Avis; Alfredo Martinez; Jordi Tauler; Enrique Zudaire; Anatoly Mayburd; Raed Abu-Ghazaleh; Frank Ondrey; James L. Mulshine

2005-01-01

127

Carrageenans inhibit growth-factor binding.  

PubMed Central

Carrageenans, a family of polysulphated carbohydrates, inhibited binding of basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGF beta 1) and platelet-derived growth factor (PDGF). iota-Carrageenan was the most potent bFGF antagonist (IC50 = 0.4 +/- 0.1 microgram/ml), kappa-carrageenan was the most potent PDGF antagonist (IC50 = 1.7 +/- 1.3 micrograms/ml) and lambda-carrageenan was the most potent TGF beta 1 antagonist (IC50 = 19 +/- 2 micrograms/ml). None of the carrageenans, at concentrations up to 200 micrograms/ml, inhibited binding of insulin-like growth factor 1 or transforming growth factor alpha. Carrageenans are selective growth-factor antagonists and have potential for the treatment of disorders associated with the over-production of certain growth factors.

Hoffman, R

1993-01-01

128

Novel Bioactivity of Ellagic Acid in Inhibiting Human Platelet Activation  

PubMed Central

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.

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

129

Inhibition and Facilitation of Nucleic Acid Amplification  

Microsoft Academic Search

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

IAN G. WILSON

1997-01-01

130

Recovery of Saccharomyces cerevisiae from ethanol - induced growth inhibition  

SciTech Connect

Ethanol caused altered mobility of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene in plasma membrane preparations of Saccharomyces cerevisiae. Because lipids had been shown to protect yeast cells against ethanol toxicity, sterols, fatty acids, proteins, and combinations of these were tested; however, protection from growth inhibition was not seen. Ethanol-induced, prolonged lag periods and diminished growth rates in S. cerevisiae were reduced by an autoconditioning of the medium by the inoculum.

Walker-Caprioglio, H.M.; Rodriguez, R.J.; Parks, L.W.

1985-09-01

131

Recovery of Saccharomyces cerevisiae from ethanol - induced growth inhibition  

Microsoft Academic Search

Ethanol caused altered mobility of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene in plasma membrane preparations of Saccharomyces cerevisiae. Because lipids had been shown to protect yeast cells against ethanol toxicity, sterols, fatty acids, proteins, and combinations of these were tested; however, protection from growth inhibition was not seen. Ethanol-induced, prolonged lag periods and diminished growth rates in S. cerevisiae were reduced by

H. M. Walker-Caprioglio; R. J. Rodriguez; L. W. Parks

1985-01-01

132

Recovery of Saccharomyces cerevisiae from ethanol-induced growth inhibition.  

PubMed Central

Ethanol caused altered mobility of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene in plasma membrane preparations of Saccharomyces cerevisiae. Because lipids had been shown to protect yeast cells against ethanol toxicity, sterols, fatty acids, proteins, and combinations of these were tested; however, protection from growth inhibition was not seen. Ethanol-induced, prolonged lag periods and diminished growth rates in S. cerevisiae were reduced by an autoconditioning of the medium by the inoculum.

Walker-Caprioglio, H M; Rodriguez, R J; Parks, L W

1985-01-01

133

Oral bacteria inhibit Helicobacter pylori growth  

Microsoft Academic Search

Various oral bacterial species were found to inhibit the growth of Helicobacter pylori strains. The growth inhibitory activities of most of these oral bacteria were adversely affected by heating at 80°C for 60 min or by protease treatment, indicating that these bacteria produce bacteriocin-like inhibitory proteins against H. pylori strains. The antagonistic effects of oral bacteria against H. pylori may

Kazuyuki Ishihara; Tadashi Miura; Ryuta Kimizuka; Yoko Ebihara; Yoshio Mizuno; Katsuji Okuda

1997-01-01

134

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

Microsoft Academic Search

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

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

135

Decitabine and suberoylanilide hydroxamic acid (SAHA) inhibit growth of ovarian cancer cell lines and xenografts while inducing expression of imprinted tumor suppressor genes, apoptosis, G2/M arrest and autophagy  

PubMed Central

BACKGROUND Epigenetic therapy has had a significant impact on the management of hematologic malignancies, but its role in the treatment of ovarian cancer remains to be defined. We have shown earlier that treatment of ovarian and breast cancer cells with DNA methyltransferase and HDAC inhibitors can upregulate expression of imprinted tumor suppressors. In this study, demethylating agents and HDAC inhibitors were tested for their ability to induce re-expression of tumor suppressor genes, inhibiting growth of ovarian cancer cells in culture and in xenografts. METHODS Ovarian cancer cells (Hey and SKOv3) were treated with demethylating agents [decitabine (DAC), azacytidine (AZA)] or HDAC inhibitors [(suberoylanilide hydroxamic acid (SAHA), trichosporin A (TSA)] to determine their impact on cellular proliferation, cell cycle regulation, apoptosis, autophagy and re-expression of ARHI and PEG3, two growth inhibitory imprinted tumor suppressor genes. The in vivo activity of DAC and SAHA was assessed in a Hey xenograft model. RESULTS A combination of DAC and SAHA produced synergistic inhibition of Hey and SKOv3 growth, by apoptosis and cell cycle arrest. DAC induced autophagy in Hey cells that could be enhanced by SAHA. Treatment with both agents induced re-expression of ARHI and PEG3 in cultured cells and in xenografts, correlating with growth inhibition. Knockdown of ARHI decreased DAC-induced autophagy. DAC and SAHA inhibited growth of Hey xenografts and induced autophagy in vivo. CONCLUSION A combination of DAC and SAHA inhibited ovarian cancer growth while inducing apoptosis, G2/M arrest, autophagy and re-expression of imprinted tumor suppressor genes.

Chen, Min-Yu; Liao, Warren S.-L.; Lu, Zhen; Bornmann, William G.; Hennessey, Violeta; Washington, Michele N.; Rosner, Gary L.; Yu, Yinhua; Ahmed, Ahmed Ashour; Bast, Robert C.

2011-01-01

136

HOXA5 acts directly downstream of retinoic acid receptor beta and contributes to retinoic acid-induced apoptosis and growth inhibition.  

PubMed

The promise of retinoids as chemopreventive agents in breast cancer is based on the differentiation and apoptosis induced upon their binding to the retinoic acid (RA) receptor beta (RARbeta). We have previously shown that HOXA5 induces apoptosis in breast cancer cells. In this study, we investigated whether RA/RARbeta and HOXA5 actions intersect to induce apoptosis and differentiation in breast cancer cells. We found that HOXA5 expression can be induced by RA only in RARbeta-positive breast cancer cells. We have, for the first time, identified the RA response element in HOXA5, which was found to be located in the 3' end of the gene. Chromatin immunoprecipitation assays showed that RARbeta binds directly to this region in vivo. Overexpression of RARbeta strongly enhances RA responsiveness, and knocking down RARbeta expression abolishes RA-mediated induction of HOXA5 expression in breast cancer cells. In addition, there is coordinated loss of both HOXA5 and RARbeta expression during neoplastic transformation and progression in the breast epithelial cell model, MCF10A. Knockdown of HOXA5 expression partially abrogates retinoid-induced apoptosis and promotes cell survival upon RA treatment. These results strongly suggest that HOXA5 acts directly downstream of RARbeta and may contribute to retinoid-induced anticancer and chemopreventive effects. PMID:17804711

Chen, Hexin; Zhang, Huiping; Lee, Jishin; Liang, Xiaohui; Wu, Xinyan; Zhu, Tao; Lo, Pang-Kuo; Zhang, Xiaokun; Sukumar, Saraswati

2007-09-01

137

Acidic Fibroblast Growth Factor Promotes Vascular Repair  

NASA Astrophysics Data System (ADS)

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

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

1991-10-01

138

All-trans retinoic acid combined with 5-Aza-2'-deoxycitidine induces C/EBP? expression and growth inhibition in MLL-AF9-positive leukemic cells.  

PubMed

The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2'-deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein ? (C/EBP?) 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?, C/EBP?, 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. PMID:23063977

Fujiki, Atsushi; Imamura, Toshihiko; Sakamoto, Kenichi; Kawashima, Sachiko; Yoshida, Hideki; Hirashima, Yoshifumi; Miyachi, Mitsuru; Yagyu, Shigeki; Nakatani, Takuya; Sugita, Kanji; Hosoi, Hajime

2012-10-10

139

Acid Inhibition and the Acid Rebound Effect  

Microsoft Academic Search

Acid secretion from gastric parietal cells is a result of a complex interaction between different stimulatory and inhibitory mediators. One of the most important mediators is gastrin, which stimulates gastric acid secretion from parietal cells mostly indirectly, by the release of histamine from enterochromaffin-like (ECL) cells. Therapy with antisecretory agents leads to hypergastrinemia, mucosal hyperplasia and increased ECL cell mass,

Marko Duvnjak

2011-01-01

140

Acid inhibition and the acid rebound effect.  

PubMed

Acid secretion from gastric parietal cells is a result of a complex interaction between different stimulatory and inhibitory mediators. One of the most important mediators is gastrin, which stimulates gastric acid secretion from parietal cells mostly indirectly, by the release of histamine from enterochromaffin-like (ECL) cells. Therapy with antisecretory agents leads to hypergastrinemia, mucosal hyperplasia and increased ECL cell mass, which results in increase of gastric acid secretion capacity. This increased secretion capacity has been shown to manifest itself after antisecretory therapy withdrawal as rebound acid hypersecretion (RAH). Various studies have quantified acid hypersecretion after the cessation of therapy with H(2) antagonists and proton-pump inhibitors (PPIs). While most of those studies had small patient numbers, the findings generally demonstrate that RAH after H(2) antagonist therapy is of low magnitude, short duration, and has questionable clinical significance. On the contrary, acid hypersecretion after PPI therapy is more pronounced, lasts longer, and could possibly be the cause of acid-related symptoms. Potential for causing symptoms has recently been confirmed in two randomized placebo-controlled studies, and while we witness the increasing use of PPIs, RAH could become a proven cause of failure to withdraw therapy in a proportion of patients with reflux or dyspeptic symptoms. PMID:22095014

Leroti?, Ivan; Barši?, Neven; Stojsavljevi?, Sanja; Duvnjak, Marko

2011-11-16

141

Creatinine Inhibits D-Amino Acid Oxidase  

Microsoft Academic Search

Inhibition of D-amino acid oxidase (DAO) activity by various uremic retention products and guanidino compounds was investigated. Creatinine (CTN) was found to inhibit DAO at a similar concentration in the sera of uremic patients. The inhibition was competitive and the Ki value was 2.7 mM. Moreover, CTN was shown to interact with flavin adenine dinucleotide (FAD), a coenzyme of DAO.

Y. Nohara; J. Suzuki; T. Kinoshita; M. Watanabe

2002-01-01

142

INHIBITION OF AFLATOXIN BIOSYNTHESIS BY TANNIC ACID  

Technology Transfer Automated Retrieval System (TEKTRAN)

Tree nut research has demonstrated that aflatoxin (AF) biosynthesis appears to be inhibited by gallic acid (GA). It is hypothesized that the release of GA from hyrolyzable tannins present in the plant seed coat or hull tissue by fungal tannase enzyme is responsible for the observed inhibition of AF...

143

Inhibition of Vascularization in Tumor Growth  

NASA Astrophysics Data System (ADS)

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

Scalerandi, M.; Sansone, B. Capogrosso

2002-11-01

144

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

Microsoft Academic Search

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

Otmar Spring; Achim Hager

1982-01-01

145

INHIBITION OF AFLATOXIN BIOSYNTHESIS BY GALLIC ACID  

Technology Transfer Automated Retrieval System (TEKTRAN)

Aflatoxin (AF) biosynthesis is inhibited by gallic acid present in tree nuts. During invasion by Aspergillus flavus, fungal tannase releases gallic acid (GA) from the hydolyzable tannins present in the pellicle of walnut and the hull of pistachio. Previous studies have shown that GA content of the...

146

Specific bile acids inhibit hepatic fatty acid uptake  

PubMed Central

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.

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

147

Cell growth inhibition by all-trans retinoic acid in SKBR-3 breast cancer cells: involvement of protein kinase Calpha and extracellular signal-regulated kinase mitogen-activated protein kinase.  

PubMed

All-trans retinoic acid (ATRA), a synthetic derivative of vitamin A, inhibits the growth of breast cancer cells. To elucidate the mechanism by which ATRA causes cell growth inhibition, we examined changes in cell cycle and intracellular signaling pathways, focusing on protein kinase C (PKC) and mitogen-activated protein kinase (MAPK). Using the estrogen receptor-negative, retinoid receptor-positive breast cancer cell line SKRB-3, we found that treatment with ATRA significantly decreased the expression of PKCalpha, as well as reducing ERK MAPK phosphorylation. ATRA treatment leads to dephosphorylation of Rb, and consequently to G(1) arrest. Marked changes in the expression of cyclins (particularly cyclins A and E) were observed in SKBR-3 cells treated with ATRA. Using a series of pharmacological and molecular approaches, we found evidence that ATRA-induced SKBR-3 cell growth inhibition involves the deregulation of the PKCalpha-MAPK pathway. These data suggest that retinoids interfered with signal transduction pathways that are crucial for cell cycle progression, and highlight the complexities of the biological effects of retinoid derivatives. PMID:14587095

Nakagawa, Shino; Fujii, Teruhiko; Yokoyama, Goro; Kazanietz, Marcelo G; Yamana, Hideaki; Shirouzu, Kazuo

2003-11-01

148

Rapid Effects of Indoleacetic Acid and Ethylene on the Growth of Intact Pea Roots 1  

PubMed Central

Root auxanometers were used to determine the growth rates of individual intact primary roots accurately and quickly. The growth of pea (Pisum sativum L.) roots was inhibited by both indoleacetic acid and ethylene within 20 minutes. A supramaximal concentration of ethylene inhibited root growth less than did 5 to 20 ?m indoleacetic acid, indicating that inhibition of root growth by auxin was not due only to indoleacetic acid-induced ethylene production. Inhibition of root growth was largely relieved within 60 minutes of removal of both growth regulators.

Rauser, Wilfried E.; Horton, Roger F.

1975-01-01

149

Menaquinone analogs inhibit growth of bacterial pathogens.  

PubMed

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

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

2013-08-19

150

Deoxycholic Acid (DCA) Causes Ligand-independent Activation of Epidermal Growth Factor Receptor (EGFR) and FAS Receptor in Primary Hepatocytes: Inhibition of EGFR/Mitogen-activated Protein Kinase-Signaling Module Enhances DCA-induced Apoptosis  

PubMed Central

Previous studies have argued that enhanced activity of the epidermal growth factor receptor (EGFR) and the mitogen-activated protein kinase (MAPK) pathway can promote tumor cell survival in response to cytotoxic insults. In this study, we examined the impact of MAPK signaling on the survival of primary hepatocytes exposed to low concentrations of deoxycholic acid (DCA, 50 ?M). Treatment of hepatocytes with DCA caused MAPK activation, which was dependent upon ligand independent activation of EGFR, and downstream signaling through Ras and PI3 kinase. Neither inhibition of MAPK signaling alone by MEK1/2 inhibitors, nor exposure to DCA alone, enhanced basal hepatocyte apoptosis, whereas inhibition of DCA-induced MAPK activation caused ?25% apoptosis within 6 h. Similar data were also obtained when either dominant negative EGFR-CD533 or dominant negative Ras N17 were used to block MAPK activation. DCA-induced apoptosis correlated with sequential cleavage of procaspase 8, BID, procaspase 9, and procaspase 3. Inhibition of MAPK potentiated bile acid-induced apoptosis in hepatocytes with mutant FAS-ligand, but did not enhance in hepatocytes that were null for FAS receptor expression. These data argues that DCA is causing ligand independent activation of the FAS receptor to stimulate an apoptotic response, which is counteracted by enhanced ligand-independent EGFR/MAPK signaling. In agreement with FAS-mediated cell killing, inhibition of caspase function with the use of dominant negative Fas-associated protein with death domain, a caspase 8 inhibitor (Ile-Glu-Thr-Asp-p-nitroanilide [IETD]) or dominant negative procaspase 8 blocked the potentiation of bile acid-induced apoptosis. Inhibition of bile acid-induced MAPK signaling enhanced the cleavage of BID and release of cytochrome c from mitochondria, which were all blocked by IETD. Despite activation of caspase 8, expression of dominant negative procaspase 9 blocked procaspase 3 cleavage and the potentiation of DCA-induced apoptosis. Treatment of hepatocytes with DCA transiently increased expression of the caspase 8 inhibitor proteins c-FLIP-S and c-FLIP-L that were reduced by inhibition of MAPK or PI3 kinase. Constitutive overexpression of c-FLIP-s abolished the potentiation of bile acid-induced apoptosis. Collectively, our data argue that loss of DCA-induced EGFR/Ras/MAPK pathway function potentiates DCA-stimulated FAS-induced hepatocyte cell death via a reduction in the expression of c-FLIP isoforms.

Qiao, Liang; Studer, Elaine; Leach, Kevin; McKinstry, Robert; Gupta, Seema; Decker, Roy; Kukreja, Rakesh; Valerie, Kristoffer; Nagarkatti, Prakash; Deiry, Wafik El; Molkentin, Jeffrey; Schmidt-Ullrich, Rupert; Fisher, Paul B.; Grant, Steven; Hylemon, Philip B.; Dent, Paul

2001-01-01

151

Inhibition of bacterial activity in acid mine drainage  

NASA Astrophysics Data System (ADS)

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

Singh, Gurdeep; Bhatnagar, Miss Mridula

1988-12-01

152

Cellular growth inhibition by TGF-? 1 involves IRS proteins  

Microsoft Academic Search

In Mv1Lu cells, insulin partially reverses transforming growth factor-?1 (TGF-?1) growth inhibition in the presence of ?5?1 integrin antagonists. TGF-?1 appears to induce phosphorylation of IRS-2 in these cells; this is inhibited by a TGF-? antagonist known to reverse TGF-? growth inhibition. Stable transfection of 32D myeloid cells (which lack endogenous IRS proteins and are insensitive to growth inhibition by

Shuan Shian Huang; Sandra M. Leal; Chun-Lin Chen; I-Hua Liu; Jung San Huang

2004-01-01

153

Activation of phospholipase D activity in transforming growth factor-beta-induced cell growth inhibition.  

PubMed

Cells regulate phospholipase D (PLD) activity in response to numerous extracellular signals. Here, we investigated the involvement of PLD activity in transforming growth factor-beta (TGF-beta1)-mediated growth inhibition of epithelial cells. TGF-beta1 inhibits the growth of MDCK, Mv1Lu, and A-549 cells. In the presence of 0.4% butanol, TGF-beta1 induces an increase in the formation of phosphatidylbutanol, a unique product catalyzed by PLD. TGF-beta1 also induces an increase in phosphatidic acid (PA) level in A-549 and MDCK cells. TGF-beta1 induces an increase in the levels of DAG labeled with [3H]-myristic acid in A-549 and MDCK cells but not in Mv1Lu cells. No increase of DAG was observed in cells prelabeled with [3H]-arachidonic acid. The data presented suggest that PLD activation is involved in the TGF-beta1-induced cell growth inhibition. PMID:10896175

Zhou, B H; Chen, J S; Chai, M Q; Zhao, S; Liang, J; Chen, H H; Song, J G

2000-06-01

154

Lumican - derived peptides inhibit melanoma cell growth and migration.  

PubMed

Lumican, a small leucine-rich proteoglycan of the extracellular matrix, presents potent anti-tumor properties. Previous works from our group showed that lumican inhibited melanoma cell migration and tumor growth in vitro and in vivo. Melanoma cells adhered to lumican, resulting in a remodeling of their actin cytoskeleton and preventing their migration. In addition, we identified a sequence of 17 amino acids within the lumican core protein, named lumcorin, which was able to inhibit cell chemotaxis and reproduce anti-migratory effect of lumican in vitro. The aim of the present study was to characterize the anti-tumor mechanism of action of lumcorin. Lumcorin significantly decreased the growth in monolayer and in soft agar of two melanoma cell lines - mice B16F1 and human SK-MEL-28 cells - in comparison to controls. Addition of lumcorin to serum free medium significantly inhibited spontaneous motility of these two melanoma cell lines. To characterize the mechanisms involved in the inhibition of cell migration by lumcorin, the status of the phosphorylation/dephosphorylation of proteins was examined. Inhibition of focal adhesion kinase phosphorylation was observed in presence of lumcorin. Since cancer cells have been shown to migrate and to invade by mechanisms that involve matrix metalloproteinases (MMPs), the expression and activity of MMPs were analyzed. Lumcorin induced an accumulation of an intermediate form of MMP-14 (~59kDa), and inhibited MMP-14 activity. Additionally, we identified a short, 10 amino acids peptide within lumcorin sequence, which was able to reproduce its anti-tumor effect on melanoma cells. This peptide may have potential pharmacological applications. PMID:24098450

Pietraszek, Katarzyna; Brézillon, Stéphane; Perreau, Corinne; Malicka-B?aszkiewicz, Maria; Maquart, François-Xavier; Wegrowski, Yanusz

2013-10-02

155

Lumican - Derived Peptides Inhibit Melanoma Cell Growth and Migration  

PubMed Central

Lumican, a small leucine-rich proteoglycan of the extracellular matrix, presents potent anti-tumor properties. Previous works from our group showed that lumican inhibited melanoma cell migration and tumor growth in vitro and in vivo. Melanoma cells adhered to lumican, resulting in a remodeling of their actin cytoskeleton and preventing their migration. In addition, we identified a sequence of 17 amino acids within the lumican core protein, named lumcorin, which was able to inhibit cell chemotaxis and reproduce anti-migratory effect of lumican in vitro. The aim of the present study was to characterize the anti-tumor mechanism of action of lumcorin. Lumcorin significantly decreased the growth in monolayer and in soft agar of two melanoma cell lines – mice B16F1 and human SK-MEL-28 cells – in comparison to controls. Addition of lumcorin to serum free medium significantly inhibited spontaneous motility of these two melanoma cell lines. To characterize the mechanisms involved in the inhibition of cell migration by lumcorin, the status of the phosphorylation/dephosphorylation of proteins was examined. Inhibition of focal adhesion kinase phosphorylation was observed in presence of lumcorin. Since cancer cells have been shown to migrate and to invade by mechanisms that involve matrix metalloproteinases (MMPs), the expression and activity of MMPs were analyzed. Lumcorin induced an accumulation of an intermediate form of MMP-14 (~59kDa), and inhibited MMP-14 activity. Additionally, we identified a short, 10 amino acids peptide within lumcorin sequence, which was able to reproduce its anti-tumor effect on melanoma cells. This peptide may have potential pharmacological applications.

Pietraszek, Katarzyna; Brezillon, Stephane; Perreau, Corinne; Malicka-Blaszkiewicz, Maria; Maquart, Francois-Xavier; Wegrowski, Yanusz

2013-01-01

156

Method of inhibiting corrosion in acidizing wells  

SciTech Connect

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

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

1992-02-18

157

Interactions of trans -cinnamic acid, its related phenolic allelochemicals, and abscisic acid in seedling growth and seed germination of lettuce  

Microsoft Academic Search

Phenolic compounds have been identified as the most common allelochemicals produced by higher plants. Inhibitions of cinnamic acid, its related phenolic derivatives, and abscisic acid (ABA) on seedling growth and seed germination of lettuce were studied.trans-Cinnamic acid, ando-,m-, andp-coumaric acids inhibited the growth of etiolated seedlings of lettuce at concentrations higher than 10-4 M and seed germination above 10-3 M.

Hai-Hang Li; Masafumi Inoue; Hiroyuki Nishimura; Junya Mizutani; Eiji Tsuzuki

1993-01-01

158

Selenium nanoparticles inhibit Staphylococcus aureus growth  

PubMed Central

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

Tran, Phong A; Webster, Thomas J

2011-01-01

159

The novel triterpenoid C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid inhibits metastatic murine breast tumor growth through inactivation of STAT3 signaling.  

PubMed

We and others have reported that C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid (CDDO-Me) effectively inhibits the growth of multiple cancer cell types. Our previous studies indicated that prolonged CDDO-Me treatment inactivated extracellular signal-regulated kinase signaling in acute myelogenous leukemia cells. Whether treatment with CDDO-Me has an earlier effect on other proteins that are important for either signal transduction or oncogenesis is unknown. Constitutively activated signal transducer and activator of transcription 3 (STAT3) is frequently found in human breast cancer samples. Constitutively activated STAT3 was shown to up-regulate c-Myc in several types of cancer and has a feedback effect on Src and Akt. To examine the effects of CDDO-Me on STAT3 signaling in breast cancer, we used the murine 4T1 breast tumor model, which is largely resistant to chemotherapy. In vitro, after treatment of 4T1 cells with 500 nmol/L CDDO-Me for 2 h, we found (a) inactivation of STAT3, (b) inactivation of Src and Akt, (c) 4-fold reduction of c-Myc mRNA levels, (d) accumulation of cells in G(2)-M cell cycle phase, (e) abrogation of invasive growth of 4T1 cells, and (f) lack of apoptosis induction. In in vivo studies, CDDO-Me completely eliminated 4T1 breast cancer growth and lung metastases induced by 4T1 cells in mice when treatment started 1 day after tumor implantation and significantly inhibited tumor growth when started after 5 days. In vivo studies also indicated that splenic mature dendritic cells were restored after CDDO-Me treatment. In summary, these data suggest that CDDO-Me may have therapeutic potential in breast cancer therapy, in part, through inactivation of STAT3. PMID:17483332

Ling, Xiaoyang; Konopleva, Marina; Zeng, Zhihong; Ruvolo, Vivian; Stephens, L Clifton; Schober, Wendy; McQueen, Teresa; Dietrich, Martin; Madden, Timothy L; Andreeff, Michael

2007-05-01

160

CMP substitutions preferentially inhibit polysialic acid synthesis  

PubMed Central

It is widely reported that derivatives of sugar moieties can be used to metabolically label cell surface carbohydrates or inhibit a particular glycosylation. However, few studies address the effect of substitution of the cytidylmonophosphate (CMP) portion on sialyltransferase activities. Here we first synthesized 2?-O-methyl CMP and 5-methyl CMP and then asked if these CMP derivatives are recognized by ?2,3-sialyltransferases (ST3Gal-III and ST3Gal-IV), ?2,6-sialyltransferase (ST6Gal-I), and ?2,8-sialyltransferase (ST8Sia-II, ST8Sia-III, and ST8Sia-IV). We found that ST3Gal-III and ST3Gal-IV but not ST6Gal-I was inhibited by 2?-O-methyl CMP as potently as by CMP, while ST3Gal-III, ST3Gal-IV, and ST6Gal-I were moderately inhibited by 5-methyl CMP. Previously, it was reported that polysialyltransferase ST8Sia-II but not ST8Sia-IV was inhibited by CMP N-butylneuraminic acid. We found that ST8Sia-IV as well as ST8Sia-II and ST8Sia-III are inhibited by 2?-O-methyl CMP as robustly as by CMP and moderately by 5-methyl CMP. Moreover, the addition of CMP, 2?-O-methyl CMP, and 5-methyl CMP to the culture medium resulted in the decrease of polysialic acid expression on the cell surface and NCAM of Chinese hamster ovary cells. These results suggest that 2?-O-methyl CMP and 5-methyl CMP can be used to preferentially inhibit sialyltransferases, in particular, polysialyltransferases in vitro and in vivo. Such inhibition may be useful to determine the function of a carbohydrate synthesized by a specific sialyltransferase such as polysialyltransferase.

Miyazaki, Tatsuo; Angata, Kiyohiko; Seeberger, Peter H.; Hindsgaul, Ole; Fukuda, Minoru

2009-01-01

161

Isonicotinic acid hydrazide induced changes and inhibition in mycolic acid synthesis in Nocardia and related taxa.  

PubMed

The mycolic acid compositions of Nocardia rubra and related bacteria grown in media containing different concentrations of antituberculous isonicotinic acid hydrazide (INH) were determined in detail by gas chromatography-mass spectrometry. On the basis of molecular species composition, average carbon numbers of mycolic acids were calculated. In Nocardia rubra, N. lutea and Rhodococcus rhodochrous IFO-13161, the ratio of mycolic to non-mycolic fatty acids and the average carbon numbers of mycolic acids were decreased at the INH concentrations of higher than 1 microgram/ml, paralleling with the significant inhibition of growth. In above three species the synthesis of longer chain mycolic acids (longer than C44 or C46 ) was inhibited more significantly than shorter homologues such as C38 or C40 . In contrast, neither growth inhibition nor change in corynomycolic acid composition was observed in Corynebacteria xerosis and Rhodococcus rhodochrous IFO-13165 at the concentration region of INH up to 100 micrograms/ml. The direct mass fragmentographic analysis of the trimethylsilylated (TMS) derivatives of mycolic acid methyl esters, monitoring [M-15] ions of individual molecular species, revealed that the chain shortening of total mycolic acid molecule by INH occurred more greatly in more highly unsaturated subclasses than in less unsaturated subclasses. Furthermore, mass fragmentographic analysis, monitoring fragment ions (A) and (B), due to straight chain and branched chain alkyl units, respectively, demonstrated the inhibition of mycolic acids was not attributed to the shortening of alpha-alkyl chain, but to the inhibition of chain elongation of C28 to C32 straight chain meromycolic acids. It was also indicated the amounts of trehalose mono- and di- mycolate (cord factor) decreased significantly with the addition of INH (1 to 20 micrograms/ml) in the above strains. From the results obtained above, INH appeared to inhibit the synthesis of mycolic acids longer than C44 or C46 specifically by inhibiting chain elongation or desaturation of precursor long chain fatty acids longer than C28 or C30. PMID:6428369

Tomiyasu, I; Yano, I

1984-04-01

162

Manipulation of body fat composition with sterculic acid can inhibit mammary carcinomas in vivo.  

PubMed Central

Sterculic acid, a delta-9-desaturase inhibitor, administered to rats caused a rise in the stearic:oleic acid ratio of total lipids in peripheral red cells, serum and liver (P less than 0.001). As a reduction in the stearic:oleic acid ratio has been described in cancer cells, we investigated the effect of sterculic acid on tumour growth. Female F344 rats were injected subcutaneously with two different doses of sterculic acid for 4 weeks prior to, and 4 weeks following, implantation of a nitrosomethylurea-induced mammary tumour. Tumour growth was inhibited equally by the two doses of sterculic acid (P less than 0.001). A rise in the stearic:oleic acid ratio of tumours was observed in rats treated for only 16 days with sterculic acid. Manipulation of the tissue stearic:oleic acid ratio inhibits transplanted mammary tumour growth in rats.

Khoo, D. E.; Fermor, B.; Miller, J.; Wood, C. B.; Apostolov, K.; Barker, W.; Williamson, R. C.; Habib, N. A.

1991-01-01

163

Rapamycin inhibits the growth of glioblastoma.  

PubMed

The molecular target of rapamycin (mTOR) is up-regulated in glioblastoma (GBM) and this is associated with the rate of cell growth, stem cell proliferation and disease relapse. Rapamycin is a powerful mTOR inhibitor and strong autophagy inducer. Previous studies analyzed the effects of rapamycin in GBM cell lines. However, to our knowledge, no experiment was carried out to evaluate the effects of rapamycin neither in primary cells derived from GBM patients nor in vivo in brain GBM xenograft. These data are critical to get a deeper insight into the effects of such adjuvant therapy in GBM patients. In the present study, various doses of rapamycin were tested in primary cell cultures from GBM patients. These effects were compared with that obtained by the same doses of rapamycin in GBM cell lines (U87Mg). The effects of rapamycin were also evaluated in vivo, in brain tumors developed from mouse xenografts. Rapamycin, starting at the dose of 10nm inhibited cell growth both in U87Mg cell line and primary cell cultures derived from various GBM patients. When administered in vivo to brain xenografts in nude mice rapamycin almost doubled the survival time of mice and inhibited by more than 95% of tumor volume. PMID:23261661

Arcella, Antonietta; Biagioni, Francesca; Antonietta Oliva, Maria; Bucci, Domenico; Frati, Alessandro; Esposito, Vincenzo; Cantore, Giampaolo; Giangaspero, Felice; Fornai, Francesco

2012-12-19

164

Inhibitory Action of Fatty Acids on the Growth of Neisseria gonorrhoeae  

PubMed Central

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.

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

1977-01-01

165

Inhibition of calcite growth by alginate  

NASA Astrophysics Data System (ADS)

The kinetics of calcite precipitation in the presence of alginate was investigated using the constant composition technique. In the concentration range investigated (0.0002-0.005 g L -1), alginate inhibits calcite precipitation. The extent of inhibition increased with increased alginate concentration and decreased solution supersaturation. Alginate adsorption, derived from normalized calcite precipitation rates, is described satisfactorily by the Langmuir adsorption model. At lowest supersaturation, alginate adsorption onto calcite probably reaches its maximal uptake of 7.5E-4 g m -2, corresponding to surface coverage of one molecule for each 200-300 nm 2, depending on the molecular mass of alginate. This means that one alginate molecule can be bound over 100-150 Ca surface sites. Initially, on the surface of the inhibited calcite, XPS identified alginate but after further time in solution, when the system had recovered, XPS demonstrated that it disappeared from the surface, presumably buried under the newly formed calcite. The alginate affinity constant decreases with increasing supersaturation, evidence for incomplete adsorption. A simple model based on competition between growth and desorption effectively describes the observed change in the adsorption constant.

Lakshtanov, L. Z.; Bovet, N.; Stipp, S. L. S.

2011-07-01

166

INHIBITION OF TITANIUM IN FUMING NITRIC ACID  

Microsoft Academic Search

Storage tests were conducted to determine the effectiveness of oxygen in ; inhibiting the corrosion reaction of titanium in fuming nitric acid (FNA). In ; these tests, which were of 28 days duration at a temperature of 30 C, the samples ; investigated were 1\\/2-inch squares (0.020 inch thick) of commercially pure ; titanium(75A) and a binary 8%-manganese alloy(C110M). The

J. B. Rittenhouse; C. A. Papp

1958-01-01

167

Polygosumic acid, a new cadinane sesquiterpene from Polygonum viscosum , inhibits the growth of drug-resistant Escherichia coli and Staphylococcus aureus (MRSA) in vitro  

Microsoft Academic Search

Three new sesquiterpenes, 6-hydroxy-7-(1-methylethyl)-3,3a,6,7,8,8a-hexahydroazulene-1,4-dicarboxylic acid methyl ester (1, named viscozulenic acid methyl ester), 7-(1-methylethyl)-3,3a,6,7,8,8a-hexahydroazulene-1,4-dicarboxylic acid 1-methyl ester\\u000a (2, named viscoazucinic acid) and 3-oxo-1-epi-sclerosporin (3, named polygosumic acid), have been isolated from the chloroform extract of the aerial parts of Polygonum viscosum by reversed-phase preparative high performance liquid chromatography (HPLC). The structures of these compounds were established\\u000a conclusively by ultraviolet (UV),

Bidyut K. Datta; M. Mukhlesur Rahman; Alexander I. Gray; Lutfun Nahar; Syed A. Hossein; Abdurazag A. Auzi; Satyajit D. Sarker

2007-01-01

168

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

NASA Astrophysics Data System (ADS)

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

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

1993-04-01

169

Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis.  

PubMed

Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose) polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy. PMID:23983455

Li, Qingli; Lambrechts, Mark J; Zhang, Qiuyang; Liu, Sen; Ge, Dongxia; Yin, Rutie; Xi, Mingrong; You, Zongbing

2013-07-24

170

Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis  

PubMed Central

Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose) polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy.

Li, Qingli; Lambrechts, Mark J; Zhang, Qiuyang; Liu, Sen; Ge, Dongxia; Yin, Rutie; Xi, Mingrong; You, Zongbing

2013-01-01

171

Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists.  

PubMed

Cytochrome P450 (CYP) epoxygenases, CYP2C8, 2C9 and 2J2 mRNA and proteins, were expressed in prostate carcinoma (PC-3, DU-145 and LNCaP) cells. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the major arachidonic acid metabolite in these cells. Blocking EET synthesis by a selective CYP epoxygenase inhibitor (N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide [MS-PPOH]) inhibited tonic (basal) invasion and migration (motility) while exogenously added EET induced cell motility in a concentration-dependent manner. An epidermal growth factor receptor (EGFR) kinase inhibitor (AG494) or a PI3 kinase inhibitor (LY294002) inhibited cell migration and reduced 11,12-EET-induced cell migration. Importantly, synthetic EET antagonists (14,15-epoxyeicosa-5(Z)-enoic acid [14,15-EEZE], 14,15-epoxyeicosa-5(Z)-enoic acid 2-[2-(3-hydroxy-propoxy)-ethoxy]-ethyl ester [14,15-EEZE-PEG] and 14,15-epoxyeicosa-5(Z)-enoic-methylsulfonylimide [14,15-EEZE-mSI]) inhibited EET-induced cell invasion and migration. 11,12-EET induced cell stretching and myosin-actin microfilament formation as well as increased phosphorylation of EGFR and Akt (Ser473), while 14,15-EEZE inhibited these effects. These results suggest that EET induce and EET antagonists inhibit cell motility, possibly by putative EET receptor-mediated EGFR and PI3K/Akt pathways, and suggest that EET antagonists are potential therapeutic agents for prostate cancer. PMID:20804500

Nithipatikom, Kasem; Brody, Daniel M; Tang, Alan T; Manthati, Vijaya L; Falck, John R; Williams, Carol L; Campbell, William B

2010-08-27

172

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

PubMed

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. PMID:11537170

Cheung, S P; Cleland, R E

1991-01-01

173

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

Microsoft Academic Search

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

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

1981-01-01

174

In vitro algal growth inhibition by phytotoxins of Typha latifolia L  

Microsoft Academic Search

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

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

1990-01-01

175

UNIDENTIFIED GROWTH FACTOR FOR A LACTIC ACID BACTERIUM.  

PubMed

Weinman, Donald E. (University of Georgia, Athens), George K. Morris, and William L. Williams. Unidentified growth factor for a lactic acid bacterium. J. Bacteriol. 87:263-269. 1964.-Lactobacillus bulgaricus Georgia strain required an unidentified growth factor, named Georgia bulgaricus factor (GBF), when grown on a semisynthetic basal medium. Aqueous extracts of torula yeast and beef liver were the best sources of GBF. Adenine, ribonucleic acid (RNA), alkaline digests of RNA, and Mg(++) also stimulated growth, but to a considerably lesser extent than liver and yeast extracts. Several purines, pyrimidines, and related compounds also promoted growth responses in individual experiments, but not consistently. Intact deoxynucleic acid (DNA), deoxyadenylic acid (dAMP), and deoxyguanylic acid (dGMP) inhibited growth. The DNA and dAMP inhibitions were fully reversed by crude sources of GBF, while dGMP inhibition was only partially reversed. RNA reversed DNA inhibition to a small extent. GBF was stable to heat at pH 2.5 to 11 and to prolonged light exposure. It was destroyed by heating at pH 1.0. The GBF activity moved as a single component in paper chromatography. It was firmly adsorbed on charcoal and poorly soluble in organic solvents. A concentrate, 28 times more potent than liver extract, was prepared by prolonged paper chromatography. All known growth factors and biological compounds readily available were assayed for GBF activity, none of which gave a response similar to the crude extracts. Final proof that a new growth factor exists must await definite identification of the active compounds. PMID:14151043

WEINMAN, D E; MORRIS, G K; WILLIAMS, W L

1964-02-01

176

Ursolic acid, an antagonist for transforming growth factor (TGF)-?1  

Microsoft Academic Search

Transforming growth factor-? (TGF-?), a multifunctional cytokine which is involved in extracellular matrix modulation, has a major role in the pathogenesis and progression of fibrotic diseases. We now report the effects of ursolic acid on TGF-?1 receptor binding and TGF-?1-induced cellular functions in vitro. Ursolic acid inhibited [125I]-TGF-?1 receptor binding to Balb\\/c 3T3 mouse fibroblasts with an IC50 value of

Shigeru Murakami; Hajime Takashima; Mariko Sato-Watanabe; Sumi Chonan; Koji Yamamoto; Masako Saitoh; Shiuji Saito; Hiromitsu Yoshimura; Koko Sugawara; Junshan Yang; Nannan Gao; Xinggao Zhang

2004-01-01

177

Acidic polysaccharide from Phellinus linteus inhibits melanoma cell metastasis by blocking cell adhesion and invasion  

Microsoft Academic Search

The acidic polysaccharide (PL) from Phellinus linteus is an immunostimulator that has therapeutic activity against cancers. Here, we show that PL markedly inhibits melanoma cell metastasis in mice, and report that PL directly inhibits cancer cell adhesion to and invasion through the extracellular matrix, but that it has no direct effect on cancer cell growth. In addition, we found that

Sang-Bae Han; Chang Woo Lee; Jong Soon Kang; Yeo Dae Yoon; Ki Hoon Lee; Kiho Lee; Song-Kyu Park; Hwan Mook Kim

2006-01-01

178

Down-Modulation of Survivin Expression and Inhibition of Tumor Growth In Vivo by EZN-3042, A Locked Nucleic Acid Antisense Oligonucleotide  

Microsoft Academic Search

Survivin plays an important role in preventing apoptosis and permitting mitosis, and is highly expressed in various human cancers. EZN-3042 is a locked nucleic acid antisense oligonucleotide (LNA-AsODN) against survivin. We report the effects of EZN-3042 in animal models. In a chemical-induced liver regeneration model, treatment with a mouse homolog of EZN-3042 resulted in 80% down-modulation of survivin mRNA. In

Puja Sapra; Maoliang Wang; Raj Bandaru; Hong Zhao; Lee M. Greenberger; Ivan D. Horak

2010-01-01

179

Role of ? -oxidation in inhibiting Lactobacillus leichmanii by fatty acids  

Microsoft Academic Search

The effect of saturated fatty acids from 6:0 to 16:0 and oleic acid onLactobacillus leichmanii ATCC 4797 growing in non-skim-milk media was determined. The inhibition by lauric acid was higher than that obtained with any other fatty acid. A mutant (MC12) resistant to the fatty acid inhibition with high ß-oxidation activity was also studied. A positive correlation between the ability

Martha S. Núñez de Kairúz; Guillermo Oliver; Aída A. Pesce de Ruiz Holgado; Ricardo N. Farías

1983-01-01

180

Rab7 Prevents Growth Factor-Independent Survival by Inhibiting Cell-Autonomous Nutrient Transporter Expression  

Microsoft Academic Search

Growth factor withdrawal results in the endocytosis and degradation of transporter proteins for glucose and amino acids. Here, we show that this process is under the active control of the small GTPase Rab7. In the presence of growth factor, Rab7 inhibition had no effect on nutrient transporter expression. In growth factor-deprived cells, however, blocking Rab7 function prevented the clearance of

Aimee L. Edinger; Ryan M. Cinalli; Craig B. Thompson

2003-01-01

181

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

PubMed Central

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

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

2013-01-01

182

SIMPLE AROMATIC ACIDS AND THEIR SALTS IN CONTROLLING THE GROWTH OF RHIZOCTONIA SOLANI UNDER LABORATORY CONDITIONS  

Microsoft Academic Search

Rhizoctonia solani is a fungus pathogenic in many economically important plants. Ten aromatic acids were examined for activity against Rhizoctonia solani using poisoned food technique. All the acids were inhibitory to R. solani. Three of the acids, at concentrations around 0.015% (g\\/ml), completely inhibited the growth of the fungus. Efforts were made to enhance the solubility of chosen aromatic acids

D. T. U Abeytunga; W. A. Jayasundara

183

Inhibition by D-Glutamate of Growth and Glutamate Dehydrogenase Activity of Neurospora crassa  

Microsoft Academic Search

SUMMARY D-Glutamic acid (D-glU) inhibited strongly the growth of two strains of Neurospora crassa in a minimal medium. The inhibition was completely annulled by equivalent concentrations of L-glutamic acid (L-glu) or L-gluta- mine. D-G~u also inhibited glutamate dehydrogenase (GDH) and was only antagonized completely by 10 equivalents of L-glu. D-G~u in media containing L-glu increased GDH-activity, presumably by de-repression. D-G~

HADARA ARKIN; N. Grossowicz

1970-01-01

184

Azadirachtin Interacts with Retinoic Acid Receptors and Inhibits Retinoic Acid-mediated Biological Responses*  

PubMed Central

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.

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

2011-01-01

185

Relieving Mipafox Inhibition in Organophosphorus Acid Anhydrolase by Rational Design.  

National Technical Information Service (NTIS)

Organophosphate acid anhydrolase (OPAA) is a bimetalloenzyme that hydrolyzes acetylcholinesterase-inhibiting organophosphorus compounds, including fluorine-containing nerve agents such as soman pinacolyl methylphosphonoflouridate. The insecticide mipafox ...

S. P. Harvey S. S. Shah T. J. Henderson

2013-01-01

186

Prevention of 5-Fluorouracil-Caused Growth Inhibition in Sordaria fimicola  

PubMed Central

Growth (dry weight accumulation) of Sordaria fimicola in standing liquid culture (sucrose-nitrate-salts-vitamins) is inhibited by the presence of 5 ?M 5-fluorouracil in the medium. This inhibition is completely prevented by uracil, deoxyuridine, and 5-bromouracil, partly prevented (40 to 90% of growth observed without 5-fluorouracil) by uridine, thymidine, and 5-bromodeoxyuridine, and slightly prevented by trifluorothymine, cytosine, cytidine, deoxycytidine, and 5-methylcytosine (all at 0.5 to 1 mM). Thymidine and thymine riboside were without any apparent effect. Growth is also inhibited by 0.2 mM 6-azauracil, and this inhibition was completely prevented by uracil and uridine, partly prevented by deoxyuridine, 5-bromouracil, cytidine, and 5-methylcytosine, and slightly prevented by thymine, thymidine, 5-bromodeoxyuridine, cytosine, and deoxycytidine. The data suggest that the observed inhibition of growth by 5-fluorouracil is due to inhibition of both ribonucleic acid and deoxyribonucleic acid synthesis. The data also allow inferences concerning pyrimidine interconversions in S. fimicola; i.e., thymine can be anabolized to thymidylic acid without first being demethylated, although demethylation appears to occur also.

Schoen, Howard F.; Berech, John

1977-01-01

187

Prevention of 5-fluorouracil-caused growth inhibition in Sordaria fimicola.  

PubMed

Growth (dry weight accumulation) of Sordaria fimicola in standing liquid culture (sucrose-nitrate-salts-vitamins) is inhibited by the presence of 5 muM 5-fluorouracil in the medium. This inhibition is completely prevented by uracil, deoxyuridine, and 5-bromouracil, partly prevented (40 to 90% of growth observed without 5-fluorouracil) by uridine, thymidine, and 5-bromodeoxyuridine, and slightly prevented by trifluorothymine, cytosine, cytidine, deoxycytidine, and 5-methylcytosine (all at 0.5 to 1 mM). Thymidine and thymine riboside were without any apparent effect. Growth is also inhibited by 0.2 mM 6-azauracil, and this inhibition was completely prevented by uracil and uridine, partly prevented by deoxyuridine, 5-bromouracil, cytidine, and 5-methylcytosine, and slightly prevented by thymine, thymidine, 5-bromodeoxyuridine, cytosine, and deoxycytidine. The data suggest that the observed inhibition of growth by 5-fluorouracil is due to inhibition of both ribonucleic acid and deoxyribonucleic acid synthesis. The data also allow inferences concerning pyrimidine interconversions in S. fimicola; i.e., thymine can be anabolized to thymidylic acid without first being demethylated, although demethylation appears to occur also. PMID:848926

Schoen, H F; Berech, J

1977-02-01

188

Inhibition of Aluminum Oxyhydroxide Precipitation with Citric Acid  

SciTech Connect

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

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

2005-12-06

189

Retinoic Acid Inhibition of Human Breast Carcinoma Proliferation Is Accompanied by Inhibition of the Synthesis of a Mr 39,000 Protein1  

Microsoft Academic Search

Retinole acid (RA) inhibits proliferation of numerous breast carcinoma cells and prevents estrogen stimulation of growth of several estrogen receptor (KR)-positive cell lines. RA inhibition of human breast carci noma cell proliferation is associated with marked inhibition of the syn thesis of a A\\/, 39,000 protein in the ER-positive human breast carcinoma cell lines investigated. Inhibition of the synthesis of

Joseph A. Fontana; Dante Miranda; Alicia Burrows Mezu

190

Kinetics modeling of inhibition and utilization of mixed volatile fatty acids in the formation of polyhydroxyalkanoates by Ralstonia eutropha  

Microsoft Academic Search

Acetic, propionic and butyric acids are the major fermentation acids produced on acidogenesis of organic wastes such as food scraps. They can be utilized by Ralstonia eutropha as sole carbon sources for cell growth and polyhydroxyalkanoate (PHA) synthesis. The acids, however, are inhibitory and toxic to the bacterium depending on the medium pH and the total acid concentration. The inhibition

Jian Yu; Yingtao Si; Wan Keung; R. Wong

2002-01-01

191

INHIBITION OF ESCHERICHIA COLI BY p-AMINOBENZOIC ACID AND ITS REVERSAL BY p-HYDROXYBENZOIC ACID  

PubMed Central

p-Aminobenzoic acid (PABA) exerts three metabolic effects on E. coli: it acts as a normal vitamin at low concentrations, as a source of another vitamin, p-hydroxybenzoic acid (POB), at moderate concentrations, and as a growth inhibitor at high concentrations (150 to 1600 µg./ml.). The inhibition is competitively reversed by POB in 1/100 the concentration of PABA. The inhibition is also reversed to a limited extent by shikimic acid and compound X, precursors of POB. p-Nitrobenzoic acid is an inhibitory competitor of both POB and PABA. The retardation of growth produced by PABA and other competitive analogues of POB (p-nitrobenzoic acid; 4,4'-dihydroxydiphenyl sulfone; phenosulfazole) is converted to complete bacteriostasis by the addition of L-aspartic acid in a remarkably low concentration (1 µg./ml.)) without change in the competitive ratio with POB. The mechanism underlying this synergism is not clear. In contrast to wild type, mutants that require POB not only are inhibited by much lower concentrations of the above analogues, but also show inhibition by weaker competitors of POB such as p-hydroxybenzenesulfonamide, p-chlorobenzoic acid, and p-fluorobenzoic acid.

Davis, Bernard D.

1951-01-01

192

Hyaluronic acid inhibits fetal platelet function: implications in scarless healing.  

PubMed

Platelets are important for the initiation of inflammation in adults, but the role of fetal platelets in fetal wound healing is unclear because fetal dermal wounds heal with a minimal inflammatory response and lack of excessive scarring. Because fetal tissue is abundant in glycosaminoglycans (GAGs), predominantly hyaluronic acid (HA), this study was designed to test the hypothesis that HA inhibits the reactivity of platelets and thus contributes to the minimal scarring characteristic of fetal tissue repair. Platelets were isolated from 10 fetal pigs at day 80 of gestation (term, 115 days) and exposed to 0.5 mg/mL of arachidonic acid, an agent shown in prior studies to evoke maximal aggregation and degranulation of fetal platelets. The ability of HA at 0.1 and 0.5 mg/mL to inhibit this response was determined. The presence of HA resulted in a dose-dependent reduction in platelet aggregation at 180 seconds (control, 99.7 +/- 0.3%; HA [0.1 mg/mL] 91.7 +/- 3.8%; and HA [0.5 mg/mL] 48.5 +/- 9.0%; P < .005 v control). The onset of aggregation was also significantly delayed by 0.5 mg/mL of HA (13.5 +/- 2.5 seconds) compared to control (2.9 +/- 0.7 seconds), P < .05. No significant diminution of platelet aggregation could be achieved by the addition of other GAGs at similar concentrations. HA also significantly impaired the release of platelet-derived growth factor (PDGF)-AB from fetal platelets. The authors conclude that HA, the predominant GAG in fetal dermal matrix, inhibits platelet aggregation and cytokine release. This inhibition of platelet aggregation and resultant inflammatory response may explain, in part, the minimal inflammation and scarless healing characteristic of fetal dermal repair. PMID:9247229

Olutoye, O O; Barone, E J; Yager, D R; Uchida, T; Cohen, I K; Diegelmann, R F

1997-07-01

193

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

Microsoft Academic Search

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

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

1994-01-01

194

Corrosion Inhibition of Aluminium by Capparis decidua in Acidic Media  

Microsoft Academic Search

The inhibition efficiency of ethanolic extract of different parts of Capparis decidua (Ker) in acidic medium has been evaluated by mass loss and thermometric methods. Values of inhibition efficiency obtained from the two methods are in good agreement and are dependent upon the concentration of inhibitor and acid.

P. ARORA; S. KUMAR; M. K. SHARMA; S. P. MATHUR

195

Control of Growth by Picolinic Acid: Differential Response of Normal and Transformed Cells  

Microsoft Academic Search

Picolinic acid reversibly inhibits the growth of cultured cells. Fourteen other pyridine derivatives were ineffective or toxic. Untransformed normal rat kidney (NRK) cells are reversibly arrested in the G1 stage of the growth cycle as shown by cell counts, mitotic index, [3H]thymidine incorporation, and flow microfluorometry. Flow microfluorometry was used to monitor the effects of picolinic acid on numerous other

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

1977-01-01

196

Effects of abscisic acid on in vitro growth of cotton fiber  

Microsoft Academic Search

Abscisic acid (ABA) inhibits in vitro growth of cotton (Gossypium hirsutum L.) fiber and is effective only when applied during the first four days of culture started on the day of anthesis. Abscisic acid causes a small increase in potassium uptake by the ovules and also enhances leakage of potassium from them. During their period of rapid growth, fibers produced

R. S. Dhindsa; C. A. Beasley; I. P. Ting

1976-01-01

197

Actinomycin D Inhibition of Deoxyribonucleic Acid-Dependent Synthesis of Ribonucleic Acid  

Microsoft Academic Search

Minute amounts of actinomycin D inhibit the synthesis of ribonucleic acid by nuclear extracts of HeLa cells in a ribonucleic acid-synthesizing system that is dependent on deoxyribonucleic acid and requires the presence of all four ribonucleoside triphosphates. The inhibition can be reversed by adding deoxyribonucleic acid to the enzymatic reaction. These findings support the work of others on the mode

I. H. Goldberg; M. Rabinowitz

1962-01-01

198

Influence of fatty acids and bovine serum albumin on the growth of human hepatoma and immortalized human kidney epithelial cells  

Microsoft Academic Search

Summary  The protective influence of bovine serum albumin against growth inhibition caused by fatty acids was studied in human hepatoma\\u000a (HepG2) and immortalized human kidney epithelial (IHKE) cells. In general, growth inhibition by unsaturated fatty acids (0.15\\u000a mmol\\/liter) increased with increasing number of double bonds. For HepG2 cells crude albumin (1g\\/100 ml) did not greatly modify growth inhibition by arachidonic, eicosapentaenoic,

Einar Lystad; Arne T. Høstmark; Cecilie Kiserud; Aage Haugen

1994-01-01

199

Furfural and Hydroxymethylfurfural inhibition of growth and photosynthesis in Spirulina  

Microsoft Academic Search

Growth of the cyanobacteria Spirulina maxima, S. platensis and S. laxissima was stopped by 7 mM of furfural. Photosynthetic oxygen evolution was instantly inhibited when 50 mM of furfural was added, whereas 7 mM inhibited oxygen evolution only when the cells were preincubated with this compound for more than 5 h. Furfural did not inhibit methyl viologen-supported photosynthetic oxygen uptake.

Shukun Yu; Åke Forsberg; Keith Kral; Marianne Pedersén

1990-01-01

200

Inhibition of Myofibroblast Apoptosis by Transforming Growth Factor b 1  

Microsoft Academic Search

Fibroblast differentiation to the myofibroblast phenotype is associated with a -smooth-muscle actin ( a -SMA) expression and regulated by cytokines. Among these, transforming growth factor (TGF)- b 1 and interleukin (IL)-1 b can stimulate and inhibit myofibroblast differentiation, respectively. IL-1 b inhibits a -SMA expres- sion by inducing apoptosis selectively in myofibroblasts via induction of nitric oxide synthase (inducible nitric

Hong-Yu Zhang; Sem H. Phan

201

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

PubMed Central

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

2013-01-01

202

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

Microsoft Academic Search

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

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

1997-01-01

203

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

PubMed Central

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

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

2001-01-01

204

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

PubMed

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

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

205

Divalent cation-phospholipid complexes and tumor growth inhibition.  

PubMed

Growth inhibition of DS sarcomas provoked by calcitonin treatment is accompanied by an increase of calcium and magnesium in the phospholipid fraction. Changes in tumor cell membrane characteristics reflected in ionic or molecular transport modifications seem to be involved in the growth impairment phenomenon. PMID:520494

Anghileri, L J; Delbrück, H

1979-12-15

206

Mechanism of Specific Inhibition of Phototropism by Phenylacetic Acid in Corn Seedling 1  

PubMed Central

Using geotropism as a control for phototropism, compounds similar to phenylacetic acid that photoreact 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 ?-phenylpyruvic acid suggest that such compounds will specifically inhibit phototropism primarily because of their photoreactivity with flavins and not their auxin activity. For example, strong auxins, indole-3-acetic acid and naphthalene-1-acetic acid, affected both tropic responses at all concentrations tested whereas weak auxins, phenylacetic acid and naphthalene-2-acetic acid, exhibited specific inhibition. 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.

Vierstra, Richard D.; Poff, Kenneth L.

1981-01-01

207

Mechanism of specific inhibition of phototropism by phenylacetic Acid in corn seedling.  

PubMed

Using geotropism as a control for phototropism, compounds similar to phenylacetic acid that photoreact 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. For example, strong auxins, indole-3-acetic acid and naphthalene-1-acetic acid, affected both tropic responses at all concentrations tested whereas weak auxins, phenylacetic acid and naphthalene-2-acetic acid, exhibited specific inhibition. 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. PMID:16661774

Vierstra, R D; Poff, K L

1981-05-01

208

In Vitro Measurement of Pollen Tube Growth Inhibition  

PubMed Central

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.

Martin, Franklin W.

1972-01-01

209

Mullerian inhibiting substance inhibits ovarian cell growth through an Rb-independent mechanism.  

PubMed

Müllerian inhibiting substance (MIS), a transforming growth factor-beta family member, causes regression of the Müllerian duct in male embryos. MIS overexpression in transgenic mice ablates the ovary, and MIS inhibits the growth of ovarian cancer cell lines in vitro, suggesting a key role for this hormone in postnatal development of the ovary. This report describes a mechanism for MIS-mediated growth inhibition in both a human epithelial ovarian cancer cell line and a cell line derived from normal ovarian surface epithelium, which is the origin of human epithelial ovarian cancers. MIS-treated cells accumulated in the G(1) phase of the cell cycle and subsequently underwent apoptosis. MIS up-regulated the cyclin-dependent kinase inhibitor p16 through an MIS type II receptor-mediated mechanism and inhibited growth in the absence of detectable or inactive Rb protein. Prolonged treatment with MIS down-regulated the Rb-related protein p130 and increased the Rb family-regulated transcription factor E2F1, overexpression of which inhibited growth. These findings demonstrate that p16 is required for MIS-mediated growth inhibition in ovarian epithelial cells and tumor cells and suggest that up-regulation of E2F1 also plays a role in this process. PMID:10958795

Ha, T U; Segev, D L; Barbie, D; Masiakos, P T; Tran, T T; Dombkowski, D; Glander, M; Clarke, T R; Lorenzo, H K; Donahoe, P K; Maheswaran, S

2000-11-24

210

MECHANISMS IN THE INHIBITION OF MICROORGANISMS BY SORBIC ACID  

PubMed Central

York, George K. (University of California, Davis), and Reese H. Vaughn. Mechanisms in the inhibition of microorganisms by sorbic acid. J. Bacteriol. 88:411–417. 1964.—Oxidative assimilation of glucose, acetate, succinate, and fumarate by washed cells of Escherichia coli, Pseudomonas aeruginosa, and Saccharomyces cerevisiae was inhibited by concentrations of sorbic acid ranging from 15 to 105 mg per 100 ml. At higher concentrations, the oxidation of these substrates was inhibited. Oxidative phosphorylation by submicroscopic particles of E. coli was reduced by about 30% by 37 mg per 100 ml of sorbic acid. The sulfhydryl enzymes fumarase, aspartase, and succinic dehydrogenase were inhibited by sorbic acid. The loss of activity of sorbic acid after reacting with cysteine suggested that a thiol addition occurred, which is believed to be the mechanism of action against sulfhydryl enzymes or cofactors.

York, George K.; Vaughn, Reese H.

1964-01-01

211

FTY720 inhibits tumor growth and angiogenesis  

Microsoft Academic Search

De novo malignancies and recurrence of tumors are some of the biggest threats to allograft recipients subjected to chronic immunosuppression. FTY720, a synthetic myriocin analogue, is an immunosuppressant that induces apoptosis of activated lymphocytes and prevents infiltration of lymphocytes into allografts, thereby prolonging allograft survival in a dose-dependent manner. Additionally, FTY720 was shown to prevent tumor growth and metastasis. Therefore,

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

2005-01-01

212

Inhibition of Influenza Virus Ribonucleic Acid Polymerase by Ribavirin Triphosphate  

PubMed Central

Ribavirin 5?-triphosphate (RTP), derived from the broad-spectrum antiviral compound ribavirin (Virazole), can selectively inhibit influenza virus ribonucleic acid polymerase in a cell-free assay. Ribavirin and its 5?-monophosphate have no effect on the polymerase. The inhibition is competitive with respect to adenosine 5?-triphosphate and guanosine 5?-triphosphate. RTP also inhibits ApG- and GpC-stimulated influenza virus ribonucleic acid polymerase. Since ribavirin is phosphorylated in the cell, the inhibition of influenza multiplication in the cell may also be caused by RTP.

Eriksson, Bertil; Helgstrand, Erik; Johansson, Nils Gunnar; Larsson, Alf; Misiorny, Alfons; Noren, Jan Olof; Philipson, Lennart; Stenberg, Kjell; Stening, Goran; Stridh, Stig; Oberg, Bo

1977-01-01

213

Cadaverine Inhibition of Porin Plays a Role in Cell Survival at Acidic pH  

Microsoft Academic Search

When grown at acidic pH, Escherichia coli cells secrete cadaverine, a polyamine known to inhibit porin- mediated outer membrane permeability. In order to understand the physiological significance of cadaverine excretion and the inhibition of porins, we isolated an OmpC mutant that showed resistance to spermine during growth and polyamine-resistant porin-mediated fluxes. Here, we show that the addition of exogenous cadav-

Hrissi Samartzidou; Mahsa Mehrazin; Zhaohui Xu; Michael J. Benedik; Anne H. Delcour

2003-01-01

214

Prevention of5-Fluorouracil-C aused GrowthInhibition in Sordaria fimicola  

Microsoft Academic Search

cytosine, cytidine, deoxycytidine, and5- methylcytosine (all at0.5to1mM).Thymidine andthymine riboside were without any apparent effect. Growth isalso inhibited by0.2mM 6-azauracil, and this inhibition was completely prevented byuracil anduridine, partly prevented bydeoxyuridine, 5-bromouracil, cytidine, and5-methylcytosine, andslightly prevented bythymine, thymidine, 5-bromodeoxyuridine, cytosine, anddeoxycy- tidine. Thedatasuggest that theobserved inhibition ofgrowth by5-fluorouracil isduetoinhibition ofbothribonucleic acid anddeoxyribonucleic acidsynthesis. Thedataalsoallow inferences concerning pyrimidine interconversions inS. fimicola; i.e.,

HOWARD F. SCHOEN

1977-01-01

215

Iron-Chelating Compounds Produced by Soil Pseudomonads: Correlation with Fungal Growth Inhibition  

PubMed Central

Strains of Pseudomonas putida, Pseudomonas sp., and Pseudomonas aeruginosa were examined for their ability to grow in the presence of the iron chelator, ethylenediamine-di-(o-hydroxyphenylacetic acid). In vitro fungal inhibition assays showed that the isolates varied in their ability to inhibit the growth of representative fungal plant pathogens. Fungal inhibition in vitro was superior to that of previously reported Pseudomonas sp. Studies with Fusarium oxysporum forma sp. lycopersici and a susceptible tomato cultivar demonstrated that Pseudomonas putida PPU3.1 was able to significantly reduce wilt disease.

Vandenbergh, Peter A.; Gonzalez, Carlos F.; Wright, Ann M.; Kunka, Blair S.

1983-01-01

216

Transcriptional profile of maize roots under acid soil growth  

PubMed Central

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

2010-01-01

217

Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I.  

PubMed

Fab I, enoyl acyl carrier protein reductase (ENR), is an enzyme used in fatty acid synthesis. It is a single chain polypeptide in plants, bacteria, and mycobacteria, but is part of a complex polypeptide in animals and fungi. Certain other enzymes in fatty acid synthesis in apicomplexan parasites appear to have multiple forms, homologous to either a plastid, plant-like single chain enzyme or more like the animal complex polypeptide chain. We identified a plant-like Fab I in Plasmodium falciparum and modelled the structure on the Brassica napus and Escherichia coli structures, alone and complexed to triclosan (5-chloro-2-[2,4 dichlorophenoxy] phenol]), which confirmed all the requisite features of an ENR and its interactions with triclosan. Like the remarkable effect of triclosan on a wide variety of bacteria, this compound markedly inhibits growth and survival of the apicomplexan parasites P. falciparum and Toxoplasma gondii at low (i.e. IC50 congruent with150-2000 and 62 ng/ml, respectively) concentrations. Discovery and characterisation of an apicomplexan Fab I and discovery of triclosan as lead compound provide means to rationally design novel inhibitory compounds. PMID:11239932

McLeod, R; Muench, S P; Rafferty, J B; Kyle, D E; Mui, E J; Kirisits, M J; Mack, D G; Roberts, C W; Samuel, B U; Lyons, R E; Dorris, M; Milhous, W K; Rice, D W

2001-02-01

218

Inhibitions of Several Antineoplastic Drugs on Serum Sialic Acid Levels in Mice Bearing Tumors  

PubMed Central

Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, thiotepa, adriamycin, probimane, cisplatin, oxalysine, cortisone, nitrogen mustard, lycobetaine, Ara-C, harringtonine, and cyclophosphamide) on the content of sialic acids in mice blood bearing solid tumors of either S180 or Lewis lung carcinoma was observed. Different inhibitions of antineoplastic drugs on both tumor growth and serum sialic acid levels in mice bearing tumors were found. Among these antineoplastic drugs, probimane, cisplatin, nitrogen mustard, and lycobetaine were able to decrease the serum sialic acid levels in mice bearing tumors. Since these four antineoplastic drugs are all DNA chelating agents, it was proposed that the inhibition of tumor sialic acids by these drugs might be through the DNA template via two ways. Since we have found no effect of antineoplastic drugs on serum sialic acid levels in normal mice, this suggests that the inhibition of antineoplastic drugs on sialic acids is by tumor involvement.

Lu, Da-Yong; Xu, Jing; Lu, Ting-Ren; Wu, Hong-Ying; Xu, Bin

2013-01-01

219

Inhibitions of several antineoplastic drugs on serum sialic Acid levels in mice bearing tumors.  

PubMed

Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, thiotepa, adriamycin, probimane, cisplatin, oxalysine, cortisone, nitrogen mustard, lycobetaine, Ara-C, harringtonine, and cyclophosphamide) on the content of sialic acids in mice blood bearing solid tumors of either S180 or Lewis lung carcinoma was observed. Different inhibitions of antineoplastic drugs on both tumor growth and serum sialic acid levels in mice bearing tumors were found. Among these antineoplastic drugs, probimane, cisplatin, nitrogen mustard, and lycobetaine were able to decrease the serum sialic acid levels in mice bearing tumors. Since these four antineoplastic drugs are all DNA chelating agents, it was proposed that the inhibition of tumor sialic acids by these drugs might be through the DNA template via two ways. Since we have found no effect of antineoplastic drugs on serum sialic acid levels in normal mice, this suggests that the inhibition of antineoplastic drugs on sialic acids is by tumor involvement. PMID:23641340

Lu, Da-Yong; Xu, Jing; Lu, Ting-Ren; Wu, Hong-Ying; Xu, Bin

2012-11-14

220

Activation of phospholipase D activity in transforming growth factor-beta-induced cell growth inhibition  

Microsoft Academic Search

Cells regulate phospholipase D (PLD) activity in response to numerous extracellular signals. Here, we investigated the involvement of PLD activity in transforming growth factor-? (TGF-b1)-mediated growth inhibition of epithelial cells. TGF-?1 inhibits the growth of MDCK, Mv1Lu, and A-549 cells. In the presence of 0.4 % butanol, TGF-?1 induces an increase in the formation of phosphatidylbutanol, a unique product catalyzed

Bing Hong ZHOU; Jun Song CHEN; Ming Qiang CHAI; Sheng ZHAO; Jun LIANG; He Hua CHEN; Jian Guo SONG

2000-01-01

221

Ethanol inhibition of continuous anaerobic yeast growth  

Microsoft Academic Search

The inhibitory effect of ethanol on the yeast Saccharomyces cerevisiae ATCC 4126 has been studied in continuous culture under conditions where high concentrations of ethanol were produced by the yeast itself. The fermentations were carried out using a glucose, salts medium at glucose concentrations of 20, 100 and 200 gl-1. The growth function\\u000a$$\\\\mu = \\\\hat \\\\mu \\\\cdot \\\\frac{{C_s }}{{K_s

Gerhard K Hoppe; Geoffrey S Hansford

1982-01-01

222

Ethyl pyruvate administration inhibits hepatic tumor growth  

Microsoft Academic Search

EP is a potent inhibitor of HMGB1 release that has sig- nificant anti-inflammatory activities and exerts a pro- tective effect in animal models of inflammation. As in- flammation is linked to cancer growth, we hypothesized that EP would have anti-tumor activity and explored its effects in a liver tumor model. Mice injected intrapor- tally with MC38 colorectal cancer cells led

Xiaoyan Liang; A. Romo de Vivar Chavez; Nicole E. Schapiro; Patricia Loughran; Stephen H. Thorne; Andrew A. Amoscato; Herbert J. Zeh; Donna Beer-Stolz; Michael T. Lotze; Michael E. de Vera

2009-01-01

223

Extracellular cyanobacterial substances inhibit microbial growth.  

PubMed

Cyanobacteria are able to produce extracellular substances with different biological activities and behaviors. The marine cyanobacteria Anabaena sp. strain Hi 26 and Oscillatoria subtilissima strain Bo 62 cause significant color changes in their growth media, while viscosity of the medium is influenced by Rivularia sp. strain Bo 85 and Oscillatoria limnetica strain Flo 1. Sterile-filtered media, pregrown with the organisms mentioned above, were used to study the influence of changes in media bioactivity induced by "excreted substances" on the growth and/or morphological development of five related filamentous cyanobacterial species and on selected heterotrophic microorganisms. Cell lysis, empty sheaths, different lengths of filaments, or even single cells and a decrease in chlorophyll a and protein content were the characteristic changes obtained by such a "cyanobacterial assay." The use of a "precultured" medium, as demonstrated in an "agar diffusion assay," affects in varying degrees the growth of gram-positive and gram-negative heterotrophic bacteria, as well as of the yeast Saccharomyces cerevisiae. PMID:11334306

Heyduck-Söller, B; Fischer, U

2000-12-01

224

Lithium inhibits carcinoid cell growth in vitro.  

PubMed

Carcinoids are slow growing neuroendocrine tumors that often cause debilitating symptoms due to excessive secretion of hormones such as serotonin. Surgery is the only potentially curative treatment, but many patients have unresectable metastatic disease. Lithium is a non- competitive inhibitor of GSK-3 with an established safety profile. The objective of this study was to investigate the effects of lithium on carcinoid cell growth in vitro. Lithium treatment caused a dose-dependent reduction in carcinoid cancer cell (BON and H727) growth. Western blot analysis revealed increased expression of cleaved poly (ADP-ribose) polymerase (PARP), indicating the induction of apoptosis. Lithium treatment also suppressed cellular levels of serotonin and chromogranin A. In summary, lithium inactivates GSK-3, induces apoptosis, and suppresses carcinoid cancer cell growth in vitro. The drug has been used clinically since the 19(th) century to treat a variety of diseases including bipolar disorder, and its safety profile is well documented. Therefore, based on these findings, we have undertaken a clinical trial of lithium chloride in the treatment of patients with unresectable carcinoid cancer. PMID:20589165

Greenblatt, David Yu; Ndiaye, Mary; Chen, Herbert; Kunnimalaiyaan, Muthusamy

2010-05-10

225

Lithium inhibits carcinoid cell growth in vitro  

PubMed Central

Carcinoids are slow growing neuroendocrine tumors that often cause debilitating symptoms due to excessive secretion of hormones such as serotonin. Surgery is the only potentially curative treatment, but many patients have unresectable metastatic disease. Lithium is a non- competitive inhibitor of GSK-3 with an established safety profile. The objective of this study was to investigate the effects of lithium on carcinoid cell growth in vitro. Lithium treatment caused a dose-dependent reduction in carcinoid cancer cell (BON and H727) growth. Western blot analysis revealed increased expression of cleaved poly (ADP-ribose) polymerase (PARP), indicating the induction of apoptosis. Lithium treatment also suppressed cellular levels of serotonin and chromogranin A. In summary, lithium inactivates GSK-3, induces apoptosis, and suppresses carcinoid cancer cell growth in vitro. The drug has been used clinically since the 19th century to treat a variety of diseases including bipolar disorder, and its safety profile is well documented. Therefore, based on these findings, we have undertaken a clinical trial of lithium chloride in the treatment of patients with unresectable carcinoid cancer.

Greenblatt, David Yu; Ndiaye, Mary; Chen, Herbert; Kunnimalaiyaan, Muthusamy

2010-01-01

226

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

PubMed

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

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

1999-11-01

227

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

PubMed Central

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.

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

1999-01-01

228

Effects of Fatty Acids on Growth and Envelope Proteins of Bacillus subtilis  

PubMed Central

Fatty acids of different chain lengths were added to cultures of Bacillus subtilis growing in nutrient sporulation medium, and the effects of these fatty acids on growth, oxygen uptake, adenosine triphosphate (ATP) concentration, and membrane protein composition were examined. All fatty acids inhibited growth, the effect being reduced in the presence of glycolytic compounds and reversed by transfer to medium without fatty acids. The inhibition of growth was correlated with a reduction in both the rate of oxygen consumption and the concentration of ATP per cell. The concentration required to obtain a certain degree of inhibition increased with decreasing molecular weight of the fatty acid. However, the reduced nicotinamide adenine dinucleotide oxidation system of cell envelope preparations (i.e., the electron transport system) was not inhibited. Submaximal growth inhibition was accompanied by the relative increase of a membrane protein band revealed by urea-acetic acid gel electrophoresis. This increase was blocked by actinomycin or chloramphenicol. All of the above changes could also be produced by 2,4-dinitrophenol. The inhibition results are best explained by assuming that the fatty acids reversibly react with the cell membrane or proteins in it; they could either alter the membrane structure or uncouple the electron transport chain from two types of proteins, those used for ATP regeneration and others needed for the transport of certain compounds into the cells. Images

Sheu, Chingju W.; Freese, Ernst

1972-01-01

229

Differential inhibition of postnatal brain, spinal cord and body growth by a growth hormone antagonist  

Microsoft Academic Search

BACKGROUND: Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). In this study, we use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. The GHA transgene encodes a protein that inhibits the binding of GH

DL McIlwain; VB Hoke; JJ Kopchick; CR Fuller; PK Lund

2004-01-01

230

Fish oil inhibits human lung carcinoma cell growth by suppressing ILK  

PubMed Central

We previously demonstrated that synthetic peroxisome proliferator activated receptor gamma (PPAR?) ligands inhibit non-small cell lung carcinoma (NSCLC) cell growth through multiple signaling pathways. Here, we show that dietary compounds, such as fish oil (which contains certain kinds of fatty acids like ?3 and ?6 polyunsaturated fatty acids), also inhibits NSCLC cell growth by affecting PPAR? and by inhibiting the expression of integrin-linked kinase (ILK). Exogenous expression of ILK overcame, while silencing ILK enhanced the inhibitory effect of fish oil on cell growth. The inhibitor of p38 MAPK, SB239023, abrogated the inhibitory effect of fish oil on ILK expression, whereas the inhibitor of ERK, PD98059, had no effect. Transient transfection experiments showed that fish oil reduced ILK promoter activity and this effect was abolished by AP-2? siRNA and by SB239023, and by deletion of a specific portion of the ILK gene promoter. Western blot analysis and Gel mobility shift assay demonstrated that fish oil significantly induced AP-2? protein expression and AP-2 DNA binding activity in the ILK gene promoter, and that this was dependent on PPAR? activation. Blockade of AP-2? abrogated the effect of fish oil on ILK expression and on cell growth, while exogenous expression of AP-2? enhanced cell growth in the setting of fish oil exposure. Taken together, these findings demonstrate that fish oil inhibits ILK expression through activation of PPAR?- and p38 MAPK-mediated induction of AP-2?. In turn, this leads to inhibition of NSCLC cell proliferation. This study unveils a novel mechanism by which fish oil inhibits human lung cancer cell growth.

Han, ShouWei; Sun, XiaoJuan; Ritzenthaler, Jeffrey D.; Roman, Jesse

2009-01-01

231

Bacterial Ammonia Causes Significant Plant Growth Inhibition  

PubMed Central

Many and complex plant-bacteria inter-relationships are found in the rhizosphere, since plants release a variety of photosynthetic exudates from their roots and rhizobacteria produce multifaceted specialized compounds including rich mixtures of volatiles, e.g., the bouquet of Serratia odorifera 4Rx13 is composed of up to 100 volatile organic and inorganic compounds. Here we show that when growing on peptone-rich nutrient medium S. odorifera 4Rx13 and six other rhizobacteria emit high levels of ammonia, which during co-cultivation in compartmented Petri dishes caused alkalization of the neighboring plant medium and subsequently reduced the growth of A. thaliana. It is argued that in nature high-protein resource degradations (carcasses, whey, manure and compost) are also accompanied by bacterial ammonia emission which alters the pH of the rhizosphere and thereby influences organismal diversity and plant-microbe interactions. Consequently, bacterial ammonia emission may be more relevant for plant colonization and growth development than previously thought.

Weise, Teresa; Kai, Marco; Piechulla, Birgit

2013-01-01

232

Growth of nitric acid hydrates on thin sulfuric acid films  

NASA Astrophysics Data System (ADS)

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 × 10-4 Torr H2O and 1 - 2.5 × 10-6 Torr HNO3) and subjected to cooling and heating cycles. FTIR spectroscopy was used to probe the phase of the sulfuric acid and to identify the HNO3/H2O films that condensed. Nitric acid trihydrate (NAT) was observed to grow on crystalline sulfuric acid tetrahydrate (SAT) films. NAT also condensed in/on supercooled H2SO4 films without causing crystallization of the sulfuric acid. This growth is consistent with NAT nucleation from ternary solutions as the first step in PSC formation.

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

1994-05-01

233

Novel Bifunctional Inhibitor of Xylanase and Aspartic Protease: Implications for Inhibition of Fungal Growth  

PubMed Central

A novel bifunctional inhibitor (ATBI) from an extremophilic Bacillus sp. exhibiting an activity against phytopathogenic fungi, including Alternaria, Aspergillus, Curvularia, Colletotricum, Fusarium, and Phomopsis species, and the saprophytic fungus Trichoderma sp. has been investigated. The 50% inhibitory concentrations of ATBI ranged from 0.30 to 5.9 ?g/ml, whereas the MIC varied from 0.60 to 3.5 ?g/ml for the fungal growth inhibition. The negative charge and the absence of periodic secondary structure in ATBI suggested an alternative mechanism for fungal growth inhibition. Rescue of fungal growth inhibition by the hydrolytic products of xylanase and aspartic protease indicated the involvement of these enzymes in cellular growth. The chemical modification of Asp or Glu or Lys residues of ATBI by 2,4,6-trinitrobenzenesulfonic acid and Woodward's reagent K, respectively, abolished its antifungal activity. In addition, ATBI also inhibited xylanase and aspartic protease competitively, with Ki values 1.75 and 3.25 ?M, respectively. Our discovery led us to envisage a paradigm shift in the concept of fungal growth inhibition for the role of antixylanolytic activity. Here we report for the first time a novel class of antifungal peptide, exhibiting bifunctional inhibitory activity.

Dash, Chandravanu; Ahmad, Absar; Nath, Devyani; Rao, Mala

2001-01-01

234

Inhibition of Chlamydia trachomatis growth by recombinant tumor necrosis factor.  

PubMed Central

Purified human recombinant tumor necrosis factor (rTNF) alpha inhibited the growth of Chlamydia trachomatis (L2/434/Bu) in HEp-2 cell cultures. The inhibition of C. trachomatis yield could be achieved even when the rTNF alpha (200 ng/ml) was added up to 12 h after infection. The effect of rTNF alpha on chlamydial infection was synergistic with that of gamma interferon. Images

Shemer-Avni, Y; Wallach, D; Sarov, I

1988-01-01

235

Inhibition of miRNA Maturation by Peptide Nucleic Acids.  

PubMed

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

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

2014-01-01

236

Corrosion Inhibition of a Green Scale Inhibitor Polyepoxysuccinic Acid  

Microsoft Academic Search

The corrosion inhibition of a green scale inhibitor, polyepoxysuccinic acid (PESA) was studied based on dynamic tests. It is found that when PESA is used alone, it had good corrosion inhibition. So, PESA should be included in the category of corrosion inhibitors. It is not only a kind of green scale inhibitor, but also a green corrosion inhibitor. The synergistic

Rong Chun XIONG; Qing ZHOU; Gang WEI

237

MG-132 Inhibits Carcinoid Growth and Alters the Neuroendocrine Phenotype  

PubMed Central

Background Carcinoid cancers are the most common neuroendocrine (NE) tumors and limited treatment options exist. The inhibition of Glycogen Synthase Kinase-3? (GSK-3?) has been shown to be a potential therapeutic target to the treatment of carcinoid disease. In this study we investigate the ability of MG-132, a proteasome inhibitor, to inhibit carcinoid growth, the neuroendocrine phenotype and its association with GSK-3?. Materials and methods Human pulmonary (NCI-H727) and gastrointestinal (BON) carcinoid cells were treated with MG-132 (0 to 4µM). Cellular growth was measured by the 3-[4,5-dimethylthiazole-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Levels of total and phosphorylated GSK-3? and the NE markers chromogranin A (CgA), Achaete-Scute complex-like 1 (ASCL1) as well as the apoptotic markers poly (ADP-ribose) polymerase (PARP) and cleaved caspase-3 were determined by Western blot. Results Treating carcinoid cells with MG-132 resulted in growth inhibition, a dose dependent inhibition of CgA and ASCL1 as well as an increase in the levels of cleaved PARP and cleaved caspase-3. Additionally an increase in the level of phosphorylated GSK-3? was observed. Conclusion MG-132 inhibits cellular growth and the neuroendocrine phenotype. This proteasome inhibitor warrants further preclinical investigation as a possible therapeutic strategy for intractable carcinoid disease.

Chen, Jui-yu; Cook, Mackenzie R.; Pinchot, Scott N.; Kunnimalaiyaan, Muthusamy; Chen, Herbert

2009-01-01

238

Salicylate Accumulation Inhibits Growth at Chilling Temperature in Arabidopsis  

Microsoft Academic Search

The growth of Arabidopsis plants in chilling conditions could be related to their levels of salicylic acid (SA). Plants with the SA hydroxylase NahG transgene grew at similar rates to Col-0 wild types at 23C, and growth of both genotypes was slowed by transfer to 5C. However, at 5C, NahG plants displayed relative growth rates about one-third greater than Col-0,

Ian M. Scott; Shannon M. Clarke; Jacqueline E. Wood; Luis A. J. Mur

2004-01-01

239

Protease inhibition by oleic acid transfer from chronic wound dressings to albumin.  

PubMed

High elastase and cathepsin G activities have been observed in chronic wounds to inhibit healing through degradation of growth factors, cytokines, and extracellular matrix proteins. Oleic acid is a non-toxic elastase inhibitor. Cotton wound dressing material was characterized as a transfer carrier for affinity uptake of oleic acid by albumin under conditions mimicking chronic wounds. The mechanism of oleic acid uptake from cotton and binding by albumin was examined with both intact dressings and cotton fiber-designed chromatography. Raman spectra of the albumin-oleic acid complexes under liquid equilibrium conditions revealed fully saturated albumin-oleic acid complexes with a 1:1 weight ratio of albumin:oleic acid. Liquid-solid equilibrium conditions revealed oleic acid transfer from cotton to albumin at 27 mole equivalents of oleic acid per mole albumin. Comparing oleic acid formulated wound dressings for dose dependent ability to lower elastase activity, we found cotton gauze>hydrogel>hydrocolloid. In contrast, the cationic serine protease cathepsin G was inhibited by oleic acid within a narrow range of oleic acid-cotton formulations. 2% albumin was sufficient to transfer quantities of oleic acid necessary to achieve a significant elastase-lowering effect. Oleic acid 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. PMID:17570626

Edwards, J Vincent; Howley, Phyllis; Davis, Rachel; Mashchak, Andrew; Goheen, Steven C

2007-03-19

240

Inhibition of Ca 2+\\/calmodulin-dependent protein kinase or epidermal growth factor receptor tyrosine kinase abolishes lysophosphatidic acid-mediated DNA-synthesis in human myometrial smooth muscle cells  

Microsoft Academic Search

Human myometrial smooth muscle cells (SMCs) were used to evaluate the proliferative activity of lysophosphatidic acid (LPA). This study specifically focuses on the role of Ca2+\\/calmodulin-dependent protein (CaM) kinase and epidermal growth factor (EGF) receptor tyrosine kinase. Myometrial SMCs were cultured from biopsies taken at Cesarean sections. The expression of LPA receptors was determined by reverse transcriptase polymerase chain reaction

Ulrika K. Nilsson; Samuel P. S. Svensson

2003-01-01

241

TGF-? Inhibition Restores Terminal Osteoblast Differentiation to Suppress Myeloma Growth  

PubMed Central

Background Multiple myeloma (MM) expands almost exclusively in the bone marrow and generates devastating bone lesions, in which bone formation is impaired and osteoclastic bone resorption is enhanced. TGF-?, a potent inhibitor of terminal osteoblast (OB) differentiation, is abundantly deposited in the bone matrix, and released and activated by the enhanced bone resorption in MM. The present study was therefore undertaken to clarify the role of TGF-? and its inhibition in bone formation and tumor growth in MM. Methodology/Principal Findings TGF-? suppressed OB differentiation from bone marrow stromal cells and MC3T3-E1 preosteoblastic cells, and also inhibited adipogenesis from C3H10T1/2 immature mesenchymal cells, suggesting differentiation arrest by TGF-?. Inhibitors for a TGF-? type I receptor kinase, SB431542 and Ki26894, potently enhanced OB differentiation from bone marrow stromal cells as well as MC3T3-E1 cells. The TGF-? inhibition was able to restore OB differentiation suppressed by MM cell conditioned medium as well as bone marrow plasma from MM patients. Interestingly, TGF-? inhibition expedited OB differentiation in parallel with suppression of MM cell growth. The anti-MM activity was elaborated exclusively by terminally differentiated OBs, which potentiated the cytotoxic effects of melphalan and dexamethasone on MM cells. Furthermore, TGF-? inhibition was able to suppress MM cell growth within the bone marrow while preventing bone destruction in MM-bearing animal models. Conclusions/Significance The present study demonstrates that TGF-? inhibition releases stromal cells from their differentiation arrest by MM and facilitates the formation of terminally differentiated OBs, and that terminally differentiated OBs inhibit MM cell growth and survival and enhance the susceptibility of MM cells to anti-MM agents to overcome the drug resistance mediated by stromal cells. Therefore, TGF-? appears to be an important therapeutic target in MM bone lesions.

Takeuchi, Kyoko; Abe, Masahiro; Hiasa, Masahiro; Oda, Asuka; Amou, Hiroe; Kido, Shinsuke; Harada, Takeshi; Tanaka, Osamu; Miki, Hirokazu; Nakamura, Shingen; Nakano, Ayako; Kagawa, Kumiko; Yata, Kenichiro; Ozaki, Shuji; Matsumoto, Toshio

2010-01-01

242

Extracellular calcium increases bisphosphonate-induced growth inhibition of breast cancer cells  

PubMed Central

Introduction Bisphosphonates have become standard therapy for the treatment of skeletal complications related to breast cancer. Although their therapeutic effects mainly result from an inhibition of osteoclastic bone resorption, in vitro data indicate that they also act directly on breast cancer cells, inhibiting proliferation and inducing apoptosis. Methods The present study examined the effects of calcium (from 0.6 to 2.0 mmol/l) on the antitumour activity of the bisphosphonate ibandronate (1 to 1,000 nmol/l) on MDA-MB-231 and MCF-7 breast cancer cells. Cell culture densities were determined using crystal violet staining assay. Apoptotic cell death was assessed by annexin V-phycoerythrin and 7-amino-actinomycin double staining. Results At low calcium concentration, 30 ?mol/l ibandronate had no effect on MDA-MB-231 cells growth and only slightly inhibited MCF-7 cells growth. Higher calcium levels significantly increased growth inhibition as well as cell apoptosis induced by ibandronate. We observed similar effects with zoledronic acid. Of note, enhancement of ibandronate-induced growth inhibition was also observed in other breast cancer cell lines (T-47D, ZR-75, Hs-578T and BT-549 cells). The growth inhibitory effect of ibandronate in the presence of high concentrations of calcium was partly suppressed by the calcium chelator EGTA (ethylene glycol tetra-acetic acid). In addition, in the presence of calcium at high concentrations, cells accumulated more [14C]ibandronate than at low calcium concentrations. We obtained further evidence of enhancement of cellular ibandronate accumulation by calcium by demonstrating that high calcium levels increased the inhibition of protein prenylation induced by the bisphosphonate. Conclusion Altogether, our data suggest that extracellular calcium, probably through its binding to ibandronate, markedly increased its cellular accumulation and its inhibitory activity on breast tumour cells. Thus, calcium released during the process of tumour-induced osteolysis might enhance the antitumour effects of bisphosphonates and contribute to their therapeutic efficacy.

Journe, Fabrice; Kheddoumi, Naima; Chaboteaux, Carole; Duvillier, Hugues; Laurent, Guy; Body, Jean-Jacques

2008-01-01

243

Lauric acid inhibits the maturation of vesicular stomatitis virus  

Microsoft Academic Search

In the presence of lauric acid (C12), the production of infectious vesicular stomatitis virus (VSV) was inhibited in a dose-dependent manner. The inhibitory effect was reversible: after removal of C12 the antiviral effect disappeared. In addition, the chain length of the monocarboxylic acids proved to be crucial, as those with shorter or longer chains were less effective or had no

Beate Hornung; Eberhard Amtmann; Gerhard Sauer

1994-01-01

244

Inhibition of palmito ( Acanthophoenix rubra) polyphenol oxidase by carboxylic acids  

Microsoft Academic Search

The inhibition of palmito (Acanthophoenix rubra) polyphenol oxidase (PPO) is reported. Recently, two forms of palmito PPO were partially purified by hydrophobic chromatography. Inhibitory effects of various carboxylic acids on these two forms have been studied. Both forms showed identical behaviour towards the inhibitors studied. Cinnamic acid was found to have the greatest inhibitory effect (Ki = 0·06 mM). When

Christine Robert; Claude Rouch; Frédéric Cadet

1997-01-01

245

Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas  

Microsoft Academic Search

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

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

246

Cytostatic inhibition of cancer cell growth by lignan secoisolariciresinol diglucoside  

Microsoft Academic Search

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

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

2010-01-01

247

Determination of Compounds Inhibiting Bacterial Growth in Sterilized Medical Devices  

Microsoft Academic Search

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

H. Shintani; E. Suzuki; M. Sakurai

2003-01-01

248

Phytotoxicity of nanoparticles: Inhibition of seed germination and root growth  

Microsoft Academic Search

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

Daohui Lin; Baoshan Xing

2007-01-01

249

Dekkera and Brettanomyces growth and utilisation of hydroxycinnamic acids in synthetic media.  

PubMed

Dekkera and Brettanomyces yeast are important spoilage organisms in a number of food and beverage products. Isolates of both genera were cultured in a defined medium and supplemented with hydroxycinnamic acids and vinylphenols to investigate their influence on growth and the formation of ethyl phenol derivatives. The growth rate of Brettanomyces species in the presence of acids was reduced, and no significant conversion to vinyl or ethyl derivatives was observed. The growth rate and substrate utilisation rates of Dekkera anomala and Dekkera bruxellensis yeast differed depending on strain and the acid precursor present. Growth of D. bruxellensis was slowed by the presence of ferulic acid with the addition of 1 mM ferulic acid completely inhibiting growth. This study provides an insight into the spoilage potential of these organisms and possible control strategies involving hydroxycinnamic acids. PMID:18322682

Harris, Victoria; Ford, Christopher M; Jiranek, Vladimir; Grbin, Paul R

2008-03-06

250

Tumor growth inhibition by ammonium chloride-induced acidosis.  

PubMed

Ammonium chloride-induced metabolic acidosis decreases the growth of various experimental tumors. Spleen exhibits the same effects. There is a sex factor which seems to affect the growth of both tumor and spleen. The observed tumor inhibition appears to be related to a systemic impairment of the anabolic mechanisms. The decrease in tumor calcium suggests that this element may play a role in the tissue growth. The possible implication of cell membrane changes and of a block in glycolysis in the acidosis effects are discussed. PMID:51839

Anghileri, L J

1975-10-01

251

Polyphosphate Inhibition of Growth of Pseudomonads From Poultry Meat  

PubMed Central

Both commercial polyphosphates and equivalent mixtures of chemically pure polyphosphates inhibited the growth of nonfluorescent pseudomonads in a synthetic medium. Fluorescent strains grew after a short lag. Inhibition was not caused by high pH, but rather by chelation of metal ions essential to the growth of the bacteria. Mg++ and the natural competitive chelators, pyoverdine and bacteriological peptone, reversed the inhibition. Chilling chicken carcasses overnight in slush ice containing 3 and 8% polyphosphates lengthened subsequent shelf-life 17 and 25%, respectively. Chickens held in continuous contact with 3 and 8% solutions of polyphosphates during storage at 2.2 C kept 17 and 67% longer, respectively. Only fluorescent strains developed in the presence of 3 and 8% polyphosphates. Chickens held in antiseptic ice containing 8% polyphosphates kept 60% longer than did those in water ice.

Elliott, R. Paul; Straka, Robert P.; Garibaldi, John A.

1964-01-01

252

Inhibited muscle amino acid uptake in sepsis.  

PubMed Central

Amino acid uptake in vivo was determined in soleus (SOL) muscle, diaphragm, heart, and liver following intravenous injection of [3H]-alpha-amino-isobutyric acid ([3H]-AIB) in rats made septic by cecal ligation and puncture (CLP) and in sham-operated controls. Muscle amino acid transport was also measured in vitro by determining uptake of [3H]-AIB in incubated extensor digitorum longus (EDL) and SOL muscles. Results were expressed as distribution ratio between [3H]-AIB in intracellular and extracellular fluid. AIB uptake in vivo was reduced by 90% in SOL and cardiac muscle and by 45% in diaphragm 16 hours after CLP. In contrast, AIB uptake by liver was almost four times higher in septic than in control animals. AIB uptake in vitro was reduced by 18% in EDL 8 hours after CLP but was not significantly altered in SOL at the same time point. Sixteen hours after CLP, AIB uptake was significantly reduced in both muscles, i.e., by 17% in EDL and by 65% in SOL. When muscles from untreated rats were incubated in the presence of plasma from septic animals (16 hours CLP) or from animals injected with endotoxin (2 mg/kg body weight), AIB uptake was reduced. Addition of endotoxin in vitro (2-200 micrograms/ml) to incubated muscles did not affect AIB uptake. The results suggest that sepsis leads to marked impairment of amino acid transport system A in muscle and that this impairment is mediated by a circulating factor that is not endotoxin. Reduced uptake of amino acids by skeletal muscle during sepsis may divert amino acids to the liver for increased gluconeogenesis and protein synthesis.

Hasselgren, P O; James, J H; Fischer, J E

1986-01-01

253

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

SciTech Connect

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

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

1994-10-01

254

Bacterial-growth inhibiting properties of multilayers formed with modified polyvinylamine.  

PubMed

New methods are needed to fight antibiotic-resistant bacteria. One alternative that has been proposed is non-leaching, permanently antibacterial surfaces. In this study, we test multilayers formed with antibacterial cationic polyvinylamine (PVAm) and polyacrylic acid (PAA) in a growth-inhibition assay. Both hydrophobically modified and native PVAm were investigated. Multilayers did reduce the bacterial growth, as compared to single layers. However, the sampling time in the assay was critical, as the treated surface area is a capacity-limiting factor. After 2h incubation, a maximal growth inhibition of more than 99% was achieved with multilayers. In contrast, after 8h we observed a maximal growth-inhibition of 40%. At longer incubation times, the surface becomes saturated, which explains the observed time-dependent effectiveness. The polymers giving multilayers with the strongest growth-inhibiting properties were native PVAm and PVAm modified with C(8), which also were the polymers with highest charge density. We therefore conclude that this effect is mainly an electrostatically driven process. Viability staining using a fluorescent stain showed a high viability rate of the adhered bacteria. The multilayers are therefore more bacteriostatic than antibacterial. PMID:21802911

Illergård, Josefin; Wågberg, Lars; Ek, Monica

2011-07-08

255

Inhibition of tumor growth by elimination of granulocytes  

PubMed Central

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

1995-01-01

256

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

PubMed

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

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

2005-02-01

257

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

PubMed Central

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.

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

2005-01-01

258

Saccharin and Cyclamate Inhibit Binding of Epidermal Growth Factor  

NASA Astrophysics Data System (ADS)

The binding of 125I-labeled mouse epidermal growth factor (EGF) to 18 cell lines, including HeLa (human carcinoma), MDCK (dog kidney cells), HTC (rat hepatoma), K22 (rat liver), HF (human foreskin), GM17 (human skin fibroblasts), XP (human xeroderma pigmentosum fibroblasts), and 3T3-L1 (mouse fibroblasts), was inhibited by saccharin and cyclamate. The human cells were more sensitive to inhibition by these sweeteners than mouse or rat cells. EGF at doses far above the physiological levels reversed the inhibition in rodent cells but not in HeLa cells. In HeLa cells, the doses of saccharin and cyclamate needed for 50% inhibition were 3.5 and 9.3 mg/ml, respectively. Glucose, 2-deoxyglucose, sucrose, and xylitol did not inhibit EGF binding. Previous studies have shown that phorbol esters, strongly potent tumor promoters, also inhibit EGF binding to tissue culture cells. To explain the EGF binding inhibition by such greatly dissimilar molecules as phorbol esters, saccharin, and cyclamate, it is suggested that they operate through the activation of a hormone response control unit.

Lee, L. S.

1981-02-01

259

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

Microsoft Academic Search

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

An-Ping Zeng; Wolf-Dieter Deckwer

1991-01-01

260

Retinol induces density-dependent growth inhibition and changes in glycolipids and LETS  

Microsoft Academic Search

CHEMICAL carcinogenesis and viral transformation are prevented or inhibited by vitamin A or its analogues1,2. Vitamin A may also play a part in membrane glycosylation as a lipid intermediate3,4. Recently, effects of retinoic acid on proliferation and density-dependent growth of mouse L cells5 and many other untransformed and transformed cells in vitro have been described6. In view of these observations,

Leonard M. Patt; Koichi Itaya; Sen-Itiroh Hakomori

1978-01-01

261

The role of ethylene in 2.4-D-induced growth inhibition  

Microsoft Academic Search

Ethylene and 2.4-dichlorophenoxyacetic acid (2.4-D) inhibited the growth of etiolated soybean (Glycine max cv. “Hawkeye”) seedlings causing tissue swelling and an increase in RNA, DNA and protein content in the subapical hypocotyl tissue. 2.4-D increased ethylene evolution from soybean seedlings and it was found that some of the effect of this herbicide on soybeans was due to the increased ethylene

R. E. Holm; F. B. Abeles

1968-01-01

262

The N domain of Smad7 is essential for specific inhibition of transforming growth factor-  signaling  

Microsoft Academic Search

nhibitory Smads (I-Smads) repress signaling by cytokines of the transforming growth factor- ? (TGF- ? ) superfamily. I-Smads have conserved carboxy-terminal Mad homology 2 (MH2) domains, whereas the amino acid sequences of their amino-terminal regions (N domains) are highly divergent from those of other Smads. Of the two different I-Smads in mammals, Smad7 inhibited signaling by both TGF- ? and

Aki Hanyu; Yasuhiro Ishidou; Takanori Ebisawa; Tomomasa Shimanuki; Takeshi Imamura; Kohei Miyazono

2001-01-01

263

Inhibition of African swine fever virus in cultured swine monocytes by phosphonoacetic acid (PAA) and by phosphonoformic acid (PFA)  

Microsoft Academic Search

Summary The use of phosphonoacetic (PAA) and phosphonoformic acid (PFA) as inhibitors of African swine fever virus (ASFV) replication in porcine monocytes\\/macrophages (MO) was investigated. At concentrations sufficient to inhibit replication, hemadsorption, and cytopathogenic damage by high inocula of ASFV, both antiviral agents were cytostatic and suppressed the DNA-synthetic growth response of porcine MO to the MO-specific colony-stimulating factor-1 (CSF-1).

F. Villinger; E. V. Genovesi; D. J. Gerstner; T. C. Whyard; R. C. Knudsen

1990-01-01

264

Inhibition of liver fibrosis by ellagic acid.  

PubMed

Chronic administration of carbon tetrachloride in liquid paraffin (1.7) ip; 0.15 ml, (20 doses) has been found to produce severe hepatotoxicity, as seen from the elevated levels of serum and liver glutamate-pyruvate transaminase, alkaline phosphatase and lipid peroxides. The chronic administration of carbon tetrachloride was also found to produce liver fibrosis as seen from pathological analysis as well as elevated liver-hydroxy proline. Oral administration of ellagic acid was found to significantly reduce the elevated levels of enzymes, lipid peroxide and liver hydroxy proline in these animals and rectified liver pathology. These results indicate that ellagic acid administration orally can circumvent the carbon tetrachloride toxicity and subsequent fibrosis. PMID:9055108

Thresiamma, K C; Kuttan, R

1996-10-01

265

Corrosion of chromium steels in inhibited acids  

SciTech Connect

The performance of chromium steels was evaluated in acidizing environments of 15% or 25% HCl, with and without surfactant additives, by means of weight-loss determinations and electrochemical impedance analysis. Corrosion rates in 15% HCl were not linear with time, hence weight-loss measurements averaged over the exposure time may be misleading when interpreted against instantaneous corrosion rates obtained from impedance measurements. The electrochemical impedance data also provided valuable information on the mechanisms of the inhibitor, the effect of acid concentration and the addition of surfactants. Commercially available inhibitor mixtures were found to protect 13% Cr steel during short term exposure, however the 25% Cr duplex stainless steel suffered selective attack of the ferrite phase irrespective of the presence of inhibitor.

Burke, P.A.; Dawson, J.L.; Bailey, G.; Woollam, R.C.

1987-01-01

266

Inhibition of Orobanche crenata Seed Germination and Radicle Growth by Allelochemicals Identified in Cereals.  

PubMed

Orobanche crenata is a parasitic weed that causes severe yield losses in important grain and forage legume crops. Cereals have been reported to inhibit O. crenata parasitism when grown intercropped with susceptible legumes, but the responsible metabolites have not been identified. A number of metabolites have been reported in cereals that have allelopathic properties against weeds, pests, and pathogens. We tested the effect of several allelochemicals identified in cereals on O. crenata seed germination and radicle development. We found that 2-benzoxazolinone, its derivative 6-chloroacetyl-2-benzoxazolinone, and scopoletin significantly inhibited O. crenata seed germination. Benzoxazolinones, l-tryptophan, and coumalic acid caused the stronger inhibition of radicle growth. Also, other metabolites reduced radicle length, this inhibition being dose-dependent. Only scopoletin caused cell necrotic-like darkening in the young radicles. Prospects for their application to parasitic weed management are discussed. PMID:24044614

Fernández-Aparicio, Mónica; Cimmino, Alessio; Evidente, Antonio; Rubiales, Diego

2013-10-01

267

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

PubMed

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

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

2009-06-15

268

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...

269

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

Microsoft Academic Search

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

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

1999-01-01

270

Ammonium affects cell viability to inhibit root growth in Arabidopsis * #  

PubMed Central

Ammonium (NH4 +) is an important form of nitrogen nutrient for most plants, yet is also a stressor for many of them. However, the primary events of NH4 + toxicity at the cellular level are still unclear. Here, we showed that NH4 + toxicity can induce the root cell death in a temporal pattern which primarily occurs in the cells of root maturation and elongation zones, and then spreads to the cells in the meristem and root cap. The results from the NH4 +-hypersensitive mutant hsn1 further confirmed our findings. Taken together, NH4 + toxicity inhibits primary root growth by inhibiting cell elongation and division and inducing root cell death.

Qin, Cheng; Yi, Ke-ke; Wu, Ping

2011-01-01

271

Apicoplast-Targeting Antibacterials Inhibit the Growth of Babesia Parasites  

PubMed Central

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

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

2012-01-01

272

Apicoplast-targeting antibacterials inhibit the growth of Babesia parasites.  

PubMed

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

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

2012-03-05

273

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

SciTech Connect

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

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

2008-02-01

274

Phosphatidic acid inhibits blue light-induced stomatal opening via inhibition of protein phosphatase 1 [corrected].  

PubMed

Stomata open in response to blue light under a background of red light. The plant hormone abscisic acid (ABA) inhibits blue light-dependent stomatal opening, an effect essential for promoting stomatal closure in the daytime to prevent water loss. However, the mechanisms and molecular targets of this inhibition in the blue light signaling pathway remain unknown. Here, we report that phosphatidic acid (PA), a phospholipid second messenger produced by ABA in guard cells, inhibits protein phosphatase 1 (PP1), a positive regulator of blue light signaling, and PA plays a role in stimulating stomatal closure in Vicia faba. Biochemical analysis revealed that PA directly inhibited the phosphatase activity of the catalytic subunit of V. faba PP1 (PP1c) in vitro. PA inhibited blue light-dependent stomatal opening but did not affect red light- or fusicoccin-induced stomatal opening. PA also inhibited blue light-dependent H(+) pumping and phosphorylation of the plasma membrane H(+)-ATPase. However, PA did not inhibit the autophosphorylation of phototropins, blue light receptors for stomatal opening. Furthermore, 1-butanol, a selective inhibitor of phospholipase D, which produces PA via hydrolysis of phospholipids, diminished the ABA-induced inhibition of blue light-dependent stomatal opening and H(+) pumping. We also show that hydrogen peroxide and nitric oxide, which are intermediates in ABA signaling, inhibited the blue light responses of stomata and that 1-butanol diminished these inhibitions. From these results, we conclude that PA inhibits blue light signaling in guard cells by PP1c inhibition, accelerating stomatal closure, and that PP1 is a cross talk point between blue light and ABA signaling pathways in guard cells. PMID:20498335

Takemiya, Atsushi; Shimazaki, Ken-ichiro

2010-05-24

275

Phosphatidic Acid Inhibits Blue Light-Induced Stomatal Opening via Inhibition of Protein Phosphatase 11[OA  

PubMed Central

Stomata open in response to blue light under a background of red light. The plant hormone abscisic acid (ABA) inhibits blue light-dependent stomatal opening, an effect essential for promoting stomatal closure in the daytime to prevent water loss. However, the mechanisms and molecular targets of this inhibition in the blue light signaling pathway remain unknown. Here, we report that phosphatidic acid (PA), a phospholipid second messenger produced by ABA in guard cells, inhibits protein phosphatase 1 (PP1), a positive regulator of blue light signaling, and PA plays a role in stimulating stomatal closure in Vicia faba. Biochemical analysis revealed that PA directly inhibited the phosphatase activity of the catalytic subunit of V. faba PP1 (PP1c) in vitro. PA inhibited blue light-dependent stomatal opening but did not affect red light- or fusicoccin-induced stomatal opening. PA also inhibited blue light-dependent H+ pumping and phosphorylation of the plasma membrane H+-ATPase. However, PA did not inhibit the autophosphorylation of phototropins, blue light receptors for stomatal opening. Furthermore, 1-butanol, a selective inhibitor of phospholipase D, which produces PA via hydrolysis of phospholipids, diminished the ABA-induced inhibition of blue light-dependent stomatal opening and H+ pumping. We also show that hydrogen peroxide and nitric oxide, which are intermediates in ABA signaling, inhibited the blue light responses of stomata and that 1-butanol diminished these inhibitions. From these results, we conclude that PA inhibits blue light signaling in guard cells by PP1c inhibition, accelerating stomatal closure, and that PP1 is a cross talk point between blue light and ABA signaling pathways in guard cells.

Takemiya, Atsushi; Shimazaki, Ken-ichiro

2010-01-01

276

Proton pump inhibition--the ultimate control of acid secretion  

SciTech Connect

The cellular mechanisms of acid secretion by the parietal cell (PC) include stimulation of membrane receptors, increases in cytosolic cyclic AMP levels, and activation of protein kinase systems. These events culminate in stimulation of a membrane-based proton pump. This consists of a non-electrogenic H+-K+-ATPase which transports H+ ions into the secretory canaliculus of the PC in exchange for the cation K+. It has been proposed that blockade of this proton pump would result in inhibition of acid secretion by all classes of acid secretagogues. Thus, the effects of membrane receptor agonists as well as any agents which augment cellular cAMP levels should be inhibited. Substituted benzimidazoles are weak bases which prevent acid secretion by blocking the H+-K+-ATPase system. In order to test the above hypothesis, we investigated the effects of the substituted benzimidazole H168/68 and cimetidine (C) on histamine (H) and 8B-stimulated acid secretion. The rabbit isolated gastric gland (IGG) model was used and acid secretion assessed by the accumulation of /sup 14/C-labeled weak base aminopyrine (AP) within the IGG in response to secretagogue stimulation. H168/68 and C both inhibited H (5 X 10(-5) M)-stimulated (/sup 14/C)AP accumulation in a concentration-dependent manner (P less than 0.05). H168/68 inhibited both H- and 8B-stimulated (/sup 14/C)AP accumulation (P less than 0.05), while C inhibited only H-stimulated (/sup 14/C)AP accumulation (P less than 0.05). H168/68 suppressed (/sup 14/C)AP below even unstimulated levels of (/sup 14/C)AP accumulation. These results support the hypothesis that H168/68 inhibits the PC distal to cAMP stimulation.

Zdon, M.J.; Ballantyne, G.H.; Schafer, D.E.; Tyshkov, M.; Cambria, R.P.; Modlin, I.M.

1986-04-01

277

14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells.  

PubMed

14,15-Epoxyeicosatrienoic acid (EET), a cytochrome P-450 epoxygenase product of arachidonic acid (AA), reduced PGE2 formation by 40-75% in porcine aortic and murine brain microvascular smooth muscle cells. The inhibition was reversed 6-10 h after removal of 14,15-EET from the medium and was regioisomeric specific; 8,9-EET produced a smaller effect, whereas 11,12- and 5,6-EET were ineffective. Although the cells converted 14,15-EET to 14, 15-dihydroxyeicosatrienoic acid (14,15-DHET), 14,15-DHET did not inhibit PGE2 formation, and the 14,15-EET-induced inhibition was potentiated by 4-phenylchalcone oxide, an epoxide hydrolase inhibitor. The inhibition occurred when substrate amounts of AA were used and was not accompanied by enhanced production of other PGs, suggesting an effect on PGH synthase; however, in murine cells, 14, 15-EET did not reduce PGH synthase mRNA or protein. Moreover, the 14, 15-EET-induced decrease in PGE2 production was overcome by increasing the concentration of AA, but not oleic acid (which is not a substrate for PGH synthase). These findings suggest that 14,15-EET competitively inhibits PGH synthase activity in vascular smooth muscle cells. The 14,15-EET-induced inhibition of PGE2 production resulted in potentiation of platelet-derived growth factor-induced smooth muscle cell proliferation, suggesting that the competitive inhibition of PGH synthase by 14,15-EET can affect growth responses in smooth muscle cells. PMID:9843811

Fang, X; Moore, S A; Stoll, L L; Rich, G; Kaduce, T L; Weintraub, N L; Spector, A A

1998-12-01

278

Glutamic-dehydrogenase activity inhibition by phenoxyacilic acids  

Microsoft Academic Search

Summary  Experiments were carried out on the effects of some phenoxyacilic acids, used as herbicides, on the glutamic-dehydrogenase\\u000a (GLDH) activity.\\u000a \\u000a 2,4-D,2,4,5-T, MCPA and Dichlorprop inhibited GLDH activity in a competitive way.\\u000a \\u000a \\u000a Phenoxyacilic acids were ranked in the following order of affinity for the enzyme on the basis of the values of the inhibition\\u000a constants: 2,4,5-T>2,4-D>MCPA>Dichlorprop; on the basis of chemical structure,

M. Polemio; G. Genchi; F. Palmieri; C. Testini

1981-01-01

279

The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice.  

PubMed

Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGFxxxb, where xxx is the amino acid number. The most studied isoforms, VEGF165 and VEGF165b have been shown to be present in tumour and normal tissues respectively. VEGF165b has been shown to inhibit VEGF- and hypoxia-induced angiogenesis, and VEGF-induced cell migration and proliferation in vitro. Here we show that overexpression of VEGF165b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF165b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF165b can inhibit growth of multiple tumour types in vivo indicating that VEGF165b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF165b expression by regulation of splicing, overexpression of VEGF165b, or therapeutic delivery of VEGF165b to tumours. PMID:18349828

Rennel, Es; Waine, E; Guan, H; Schüler, Y; Leenders, W; Woolard, J; Sugiono, M; Gillatt, D; Kleinerman, Es; Bates, Do; Harper, Sj

2008-03-18

280

Stereocomplexes Formed From Select Oligomers of Polymer d-lactic Acid (PDLA) and l-lactate May Inhibit Growth of Cancer Cells and Help Diagnose Aggressive Cancers-Applications of the Warburg Effect.  

PubMed

It is proposed that select oligomers of polymer d-lactic acid (PDLA) will form a stereocomplex with l-lactate in vivo, producing lactate deficiency in tumor cells. Those cancer cells that utilize transport of lactate to maintain electrical neutrality may cease to multiply or die because of lactate trapping, and those cancer cells that benefit from utilization of extracellular lactate may be impaired. Intracellular trapping of lactate produces a different physiology than inhibition of LDH because the cell loses the option of shuttling pyruvate to an alternative pathway to produce an anion. Conjugated with stains or fluorescent probes, PDLA oligomers may be an agent for the diagnosis of tissue lactate and possibly cell differentiation in biopsy specimens. Preliminary experimental evidence is presented confirming that PDLA in high concentrations is cytotoxic and that l-lactate forms a presumed stereocomplex with PDLA. Future work should be directed at isolation of biologically active oligomers of PDLA. PMID:21487535

Goldberg, Joel S

2011-02-15

281

Hydroxyapatite-binding peptides for bone growth and inhibition  

DOEpatents

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

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

2011-09-20

282

Growth/no growth interfaces of table olive related yeasts for natamycin, citric acid and sodium chloride.  

PubMed

The present work uses a logistic/probabilistic model to obtain the growth/no growth interfaces of Saccharomyces cerevisiae, Wickerhamomyces anomalus and Candida boidinii (three yeast species commonly isolated from table olives) as a function of the diverse combinations of natamycin (0-30 mg/L), citric acid (0.00-0.45%) and sodium chloride (3-6%). Mathematical models obtained individually for each yeast species showed that progressive concentrations of citric acid decreased the effect of natamycin, which was only observed below 0.15% citric acid. Sodium chloride concentrations around 5% slightly increased S. cerevisiae and C. boidinii resistance to natamycin, although concentrations above 6% of NaCl always favoured inhibition by this antimycotic. An overall growth/no growth interface, built considering data from the three yeast species, revealed that inhibition in the absence of citric acid and at 4.5% NaCl can be reached using natamycin concentrations between 12 and 30 mg/L for growth probabilities between 0.10 and 0.01, respectively. Results obtained in this survey show that is not advisable to use jointly natamycin and citric acid in table olive packaging because of the observed antagonistic effects between both preservatives, but table olives processed without citric acid could allow the application of the antifungal. PMID:22373571

Arroyo-López, F N; Bautista-Gallego, J; Romero-Gil, V; Rodríguez-Gómez, F; Garrido-Fernández, A

2012-02-15

283

Proteasome Inhibition by Fellutamide B Induces Nerve Growth Factor Synthesis  

PubMed Central

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

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

2008-01-01

284

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

SciTech Connect

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.

Zaldivar, J.; Ingram, L.O.

1999-07-01

285

Inhibition of growth of leukemia cells by enzymic folate depletion.  

PubMed

A new bacterial enzyme, designated as carboxypeptidase G(1), inhibited growth of the L5178Y and L1210 murine leukemias, as well as the Walker carcinoma and the human lymphoblastoid line (RPMI 4265), propogated in vitro. This enzyme hydrolyzes the glutamate moiety from both oxidized and reduced folate forms, and thus it may prove to be of value in creating rapid folate depletion in vivo. PMID:5313376

Bertino, J R; O'Brien, P; McCullough, J L

1971-04-01

286

Growth inhibition of hopanoid synthesizing bacteria by squalene cyclase inhibitors  

Microsoft Academic Search

2,3-Dihydro-2-azasqualene, its N-oxide and its N,N-diethyl analogue, as well as 2,3-dihydro-2,3-iminosqualene are potent inhibitors of the squalene to hopanoid (diplotene and diplopterol) cyclases in cell-free systems from Acetobacter pasteurianus ssp pasteurianus, Methylobacterium organophilum and Zymomonas mobilis. The inhibitory concentration giving 50% inhibition at a 120 µM squalene concentration was determined in each cases. The growth of hopanoid producing prokaryotes (with

G. Flesch; M. Rohmer

1987-01-01

287

Inhibition of mycobacterial alanine racemase activity and growth by thiadiazolidinones.  

PubMed

The genus Mycobacterium includes non-pathogenic species such as M. smegmatis, and pathogenic species such as M. tuberculosis, the causative agent of tuberculosis (TB). Treatment of TB requires a lengthy regimen of several antibiotics, whose effectiveness has been compromised by the emergence of resistant strains. New antibiotics that can shorten the treatment course and those that have not been compromised by bacterial resistance are needed. In this study, we report that thiadiazolidinones, a relatively little-studied heterocyclic class, inhibit the activity of mycobacterial alanine racemase, an essential enzyme that converts l-alanine to d-alanine for peptidoglycan synthesis. Twelve members of the thiadiazolidinone family were evaluated for inhibition of M. tuberculosis and M. smegmatis alanine racemase activity and bacterial growth. Thiadiazolidinones inhibited M. tuberculosis and M. smegmatis alanine racemases to different extents with 50% inhibitory concentrations (IC50) ranging from <0.03 to 28?M and 23 to >150?M, respectively. The compounds also inhibited the growth of these bacteria, including multidrug resistant strains of M. tuberculosis. The minimal inhibitory concentrations (MIC) for drug-susceptible M. tuberculosis and M. smegmatis ranged from 6.25?g/ml to 100?g/ml, and from 1.56 to 6.25?g/ml for drug-resistant M. tuberculosis. The in vitro activities of thiadiazolidinones suggest that this family of compounds might represent starting points for medicinal chemistry efforts aimed at developing novel antimycobacterial agents. PMID:23680030

Lee, Yashang; Mootien, Sara; Shoen, Carolyn; Destefano, Michelle; Cirillo, Pier; Asojo, Oluwatoyin A; Yeung, Kacheong R; Ledizet, Michel; Cynamon, Michael H; Aristoff, Paul A; Koski, Raymond A; Kaplan, Paul A; Anthony, Karen G

2013-05-13

288

The AF-2 region of the retinoic acid receptor alpha mediates retinoic acid inhibition of estrogen receptor function in breast cancer cells.  

PubMed

The growth of estrogen receptor (ER)-positive breast cancer cells is inhibited by all-trans-retinoic acid (RA). In the present study, estrogen (E2) induction of pS2 mRNA levels was significantly reduced within 6 h following cotreatment with RA. In transient transfection experiments, RA repressed transactivation from a vitellogenin E2-responsive element by approximately 50% and wild-type RA receptor alpha (RARalpha) or RARbeta enhanced this inhibition. Transfection of truncated RARalpha mutants terminating before or at amino acid 412 markedly decreased RA inhibition of E2-induced reporter gene activity. Expression of RARs with deletions of amino acids 413 and 414 in the transactivation-2 (AF-2) domain also reduced RA inhibition, while deletions and point mutations beyond amino acid 414 behaved like the wild-type RARalpha. RA-treated MCF-7 cells transfected with an RARalpha AF-2 region mutant were twice as sensitive to growth inhibition as untransfected and vector-transfected control cells. Thus, the AF-2 domain in the C terminus of the RARalpha mediates RA inhibition of ER-induced transcription in breast cancer cells. In addition, transcriptional interference between RARs and ERs may contribute to RA inhibition of ER-positive breast cancer cell growth. PMID:8702769

Pratt, M A; Deonarine, D; Teixeira, C; Novosad, D; Tate, B F; Grippo, J F

1996-08-23

289

Hydrogen peroxide modulates abscisic acid signaling in root growth and development in Arabidopsis  

Microsoft Academic Search

Exogenous abscisic acid (ABA) can inhibit root growth and promote formation of more root hairs in the root tip of Arabidopsis. However, the molecular mechanisms that underlie root ABA signaling are largely unknown. We report here that hydrogen peroxide\\u000a (H2O2) reduces the root growth of wild type, and the phenotype of H2O2 on the root growth is similar to ABA

Ling Bai; Yun Zhou; XiaoRan Zhang; ChunPeng Song; MingQing Cao

2007-01-01

290

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

Microsoft Academic Search

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

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

2007-01-01

291

Growth inhibition of pathogenic bacteria by sulfonylurea herbicides.  

PubMed

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

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

2012-12-21

292

Growth Inhibition of Pathogenic Bacteria by Sulfonylurea Herbicides  

PubMed Central

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

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

293

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

PubMed Central

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.

Munoz, R; Arena, M.E.; Silva, J.; Gonzalez, S.N.

2010-01-01

294

Fn14oTrail Effectively Inhibits Hepatocellular Carcinoma Growth  

PubMed Central

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

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

2013-01-01

295

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

PubMed Central

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

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

2013-01-01

296

Fatty Acid Amide Hydrolase Inhibition by Neurotoxic Organophosphorus Pesticides  

Microsoft Academic Search

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

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

2001-01-01

297

Hyaluronic acid inhibits fetal platelet function: Implications in scarless healing  

Microsoft Academic Search

Platelets are important for the initiation of inflammation in adults, but the role of fetal platelets in fetal wound healing is unclear because fetal dermal wounds heal with a minimal inflammatory response and lack of excessive scarring. Because fetal tissue is abundant in glycosaminoglycans (GAGs), predominantly hyaluronic acid (HA), this study was designed to test the hypothesis that HA inhibits

Oluyinka O Olutoye; Eleanor J Barone; Dorne R Yager; Takashi Uchida; I. Kelman Cohen; Robert F Diegelmann

1997-01-01

298

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

Microsoft Academic Search

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

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

1997-01-01

299

Retinoic Acid Inhibition of Cell Cycle Progression in MCF7 Human Breast Cancer Cells  

Microsoft Academic Search

Cell cycle analysis indicates that retinoic acid (RA) inhibition of MCF-7 cell growth occurs through induction of G1 arrest with a concomitant reduction in the proportion of cells in S and G2 + M phases. RA did not affect cyclins D1, A, and E and cyclin-dependent kinase 2 (CDK2) expression, but significantly reduced cyclin D3 and CDK4 expression after 24

Wei-Yong Zhu; Carol S. Jones; Andras Kiss; Karen Matsukuma; Sonal Amin; Luigi M. De Luca

1997-01-01

300

Inhibition of Nb2 T-lymphoma cell growth by transforming growth factor-beta.  

PubMed Central

Transforming growth factor-beta (TGF-beta) inhibits proliferation of Nb2 cells, a rat T lymphoma, in response to lactogens and interleukin-2. Prostaglandins may play an important role in the pathway through which TGF-beta exerts its inhibitory actions, because prostaglandin E2 also inhibits proliferation of Nb2 cells, and indomethacin, an inhibitor of prostaglandin synthesis, reverses the inhibitory effects of TGF-beta on Nb2 cell proliferation.

Rayhel, E J; Prentice, D A; Tabor, P S; Flurkey, W H; Geib, R W; Laherty, R F; Schnitzer, S B; Chen, R; Hughes, J P

1988-01-01

301

Keratinocyte Growth Inhibition by High-Dose Epidermal Growth Factor Is Mediated by Transforming Growth Factor ? Autoinduction: A Negative Feedback Mechanism for Keratinocyte Growth  

Microsoft Academic Search

The epidermal growth factor receptor and its ligands initiate a major signaling pathway that regulates keratinocyte growth in an autocrine manner. It is well known that high doses of epidermal growth factor receptor ligands inhibit keratinocyte growth. Recently, signal transducers and activators of transcription 1-dependent p21Waf1\\/Cip1 induction were reported to be involved in high-dose epidermal growth factor-dependent cell growth arrest

Kenshi Yamasaki; Nobuko Toriu; Yasushi Hanakawa; Yuji Shirakata; Koji Sayama; Atsushi Takayanagi; Masafumi Ohtsubo; Shinobu Gamou; Nobuyoshi Shimizu; Makiko Fujii; Kohei Miyazono; Koji Hashimoto

2003-01-01

302

Amino acids and presynaptic inhibition in the rat cuneate nucleus  

PubMed Central

1. Presynaptic inhibition was evoked in the rat cuneate nucleus by a peripheral conditioning stimulus. The dicarboxylic amino acid salts glutamate and aspartate and the neutral amino acids glycine and ?-aminobutyric acid (GABA) were topically applied to a restricted area of the cuneate nucleus and their effects on both resting primary afferent terminal excitability and the increase in excitability of afferent terminals during presynaptic inhibition determined. 2. Aspartate had no effect on either resting primary afferent terminal excitability or on the increase in excitability during presynaptic inhibition. 3. Glycine reduced both resting primary afferent terminal excitability and presynaptic inhibition. 4. Glutamate increased both resting primary afferent terminal excitability and presynaptic inhibition while GABA increased resting primary afferent terminal excitability but reduced the increase in excitability during presynaptic inhibition. 5. The convulsant alkaloids picrotoxin (given intravenously) and bicuculline (topically applied) blocked presynaptic inhibition. The blocking action of picrotoxin was overcome by topical application of GABA but not glutamate. 6. Simultaneous measurement of pre- and post-synaptic excitability in the cuneate nucleus showed that while glutamate increased excitability at both sites, GABA increased primary afferent terminal excitability but depressed post-synaptic excitability. 7. It is concluded that glycine and glutamate exert non-specific actions on primary afferent terminals similar to their effects at post-synaptic sites elsewhere in the C.N.S. while GABA depolarizes primary afferent terminals by a specific action at the same receptor site as the presynaptic inhibitory transmitter. The possibility is discussed that the presynaptic inhibitory transmitter in the cuneate nucleus is GABA or a closely related substance. ImagesPlate 1

Davidson, N.; Southwick, C. A. P.

1971-01-01

303

Inhibition of citrus fungal pathogens by using lactic acid bacteria.  

PubMed

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

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

2010-08-01

304

Epidermal growth factor inhibits cytoskeleton-related changes in the surface of parietal cells  

PubMed Central

The effect of epidermal growth factor (EGF) on gastric acid secretion was correlated with the morphological changes of the apical pole of rat parietal cells studied by transmission electron microscopy. Gastric acid secretion was stimulated by histamine, carbachol, pentagastrin, and insulin-induced hypoglycemia, and estimated by continuous recording of pH variations of gastric luminal perfusate. EGF inhibits acid secretion in these conditions. The action of the hormone also results in the arrest or reversal of the changes in shape undergone by parietal cells as they go into secretion. In view of the evidence involving cytoskeletal elements in the generation of these structural alterations, our observations suggest that the action of EGF on gastric acid secretion may be a consequence of a general effect of this hormone on cytoskeletal function.

1981-01-01

305

Soluble Epoxide Hydrolase Inhibition, Epoxygenated Fatty Acids and Nociception  

PubMed Central

The soluble epoxide hydrolase (sEH) enzyme regulates the levels of endogenous epoxygenated fatty acid (EFA) lipid metabolites by rapidly degrading these molecules. The EFAs have pleiotropic biological activities including the modulation of nociceptive signaling. Recent findings indicate that the EFAs, in particular the arachidonic acid (AA) derived epoxyeicosatrienoic acids (EETs), the docosahexaenoic acid (DHA) derived epoxydocosapentaenoic acids (EpDPEs) and eicosapentaenoic acid (EPA) derived epoxyeicosatetraenoic acids (EpETEs) are natural signaling molecules. The tight regulation of these metabolites speaks to their importance in regulating biological functions. In the past several years work on EFAs in regard to their activities in the nervous system evolved to demonstrate that these molecules are anti-inflammatory and anti-nociceptive. Here we focus on the recent advances in understanding the effects of sEH inhibition and increased EFAs on the nociceptive system and their ability to reduce pain. Evidence of their role in modulating pain signaling is given by their direct application and by inhibiting their degradation in various models of pain. Moreover, there is mounting evidence of EFAs role in the crosstalk between major nociceptive and anti-nociceptive systems which is reviewed herein. Overall the fundamental knowledge generated within the past decade indicates that orally bioavailable small molecule inhibitors of sEH may find a place in the treatment of a number of diverse painful conditions including inflammatory and neuropathic pain.

Wagner, Karen; Inceoglu, Bora; Hammock, Bruce D.

2011-01-01

306

2-Alkynoic fatty acids inhibit topoisomerase IB from Leishmania donovani.  

PubMed

2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC(50)=5.3±0.7?M. The potency of LdTopIB inhibition follows the trend 2-ODA>2-HDA>2-TDA, indicating that the effectiveness of inhibition depends on the fatty acid carbon chain length. All of the studied 2-alkynoic fatty acids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC(50)=11.0?M), but it was less effective against other protozoa, Trypanosoma cruzi (IC(50)=48.1?M) and Trypanosoma brucei rhodesiense (IC(50)=64.5?M). The antiprotozoal activity of the 2-alkynoic fatty acids, in general, followed the trend 2-ODA>2-HDA>2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound. PMID:22932312

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

2012-08-10

307

2-Alkynoic fatty acids inhibit Topoisomerase IB from Leishmania donovani  

PubMed Central

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

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

2012-01-01

308

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

Microsoft Academic Search

Prostate carcinoma frequently metastasizes to bone where the microenvironment facilitates its growth. Inhibition of bone resorption is effective in reducing tumor burden and bone destruction in prostate cancer. However, whether drugs that inhibit osteoclast function inhibit tumor growth independent of inhibition of bone resorption is unclear. Calcium is released during bone resorption and the calcium sensing receptor is an important

Xin Li; Jinhui Liao; Amy J. Koh; William D. Sadler; Kenneth J. Pienta; Thomas J. Rosol; Laurie K. McCauley

2011-01-01

309

Growth inhibiting activity of lipophilic extracts from Dipsacus sylvestris Huds. roots against Borrelia burgdorferi s. s. in vitro.  

PubMed

Fresh first year roots from Dipsacus sylvestris HUDS. were extracted with 70% ethanol, ethyl acetate as well as dichloromethane. Extracts were solubilized in water (lipophilic extracts with addition of polysorbate 80) and tested for their activity against Borrelia burgdorferi sensu stricto in vitro during an eight-day period using amoxicillin as standard. The hydroethanolic extract showed no growth inhibition whereas significant growth inhibiting activity could be shown in the two less polar fractions for the first time. Strongest inhibition was found in the ethyl acetate extract. The effect of polysorbate 80 on bacterial growth was examined and found to be negligible. As the nature of bioactive constituents has not been clarified yet, a micellar electrokinetic capillary chromatography fingerprint analysis for a methanolic extract was applied including loganin, chlorogenic acid, cantleyoside and caffeic acid as marker substances. PMID:21901989

Liebold, T; Straubinger, R K; Rauwald, H W

2011-08-01

310

Growth of Thiobacillus ferrooxidans on formic acid  

SciTech Connect

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

Pronk, J.T.; Meijer, W.M.; Hazeu, W.; vanDijken, J.P.; Bos, P.; Kuenen, J.G. (Delft Univ. of Technology (Netherlands))

1991-07-01

311

Growth of Thiobacillus ferrooxidans on Formic Acid  

PubMed Central

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

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

1991-01-01

312

Ability of S-Methyl-L-cysteine to Annul the Inhibition of Yeast Growth by L-Ethionine and by S-Ethyl-L-cysteine  

Microsoft Academic Search

SUMMARY The inhibition of growth of a brewer's yeast and four other yeasts by L-ethionine, and the annulment of the inhibition by L-methionine were examined. S-Methyl- L-cysteine, DL-methionine sulphoxide and DL-a-amino-n-butyric acid were also able to decrease the growth inhibition. At a fivefold molar concentration, S-methyl- cysteine annulled completely the effect of ethionine on the brewer's yeast. S-Ethyl- L-cysteine was

G. A. MAW; Arthur Guinness

1961-01-01

313

Defective chloroplast development inhibits maintenance of normal levels of abscisic acid in a mutant of the Arabidopsis RH3 DEAD-box protein during early post-germination growth.  

PubMed

The plastid has its own translation system, and its ribosomes are assembled through a complex process in which rRNA precursors are processed and ribosomal proteins are inserted into the rRNA backbone. DEAD-box proteins have been shown to play roles in multiple steps in ribosome biogenesis. To investigate the cellular and physiological roles of an Arabidopsis DEAD-box protein, RH3, we examined its expression and localization and the phenotypes of rh3-4, a T-DNA insertion mutant allele of RH3. The promoter activity of RH3 is strongest in the greening tissues of 3-day and 1-week-old seedlings but reduced afterwards. Cotyledons were pale and seedling growth was retarded in the mutant. The most obvious abnormality in the mutant chloroplasts was their lack of normal ribosomes. Electron tomography analysis indicated that ribosome density in the 3-day-old mutant chloroplasts is only 20% that of wild-type chloroplasts, and the ribosomes in the mutant are smaller. These chloroplast defects in rh3-4 were alleviated in 2-week-old cotyledons and true leaves. Interestingly, rh3-4 seedlings have lower amounts of abscisic acid prior to recovery of their chloroplasts, and were more sensitive to abiotic stresses. Transcriptomic analysis indicated that nuclear genes for chloroplast proteins are down-regulated, and proteins mediating chloroplast-localized steps of abscisic acid biosynthesis are expressed to a lower extent in 1-week-old rh3-4 seedlings. Taken together, these results suggest that conversion of eoplasts into chloroplasts in young seedlings is critical for the seedlings to start carbon fixation as well as for maintenance of abscisic acid levels for responding to environmental challenges. PMID:23227895

Lee, Kwang-Hee; Park, Jiyoung; Williams, Donna S; Xiong, Yuqing; Hwang, Inhwan; Kang, Byung-Ho

2012-12-10

314

Inhibition of Carcinoma Cell Motility by Epoxyeicosatrienoic Acid (EET) Antagonists  

PubMed Central

Summary Cytochrome P450 (CYP) epoxygenases, CYP2C8, 2C9 and 2J2 mRNAs and proteins, were expressed in prostate carcinoma (PC-3, DU-145 and LNCaP) cells. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the major arachidonic acid metabolite in these cells. Blocking the EET synthesis by a selective CYP epoxygenase inhibitor (MS-PPOH) inhibited tonic (basal) invasion and migration (motility) while exogenously added EETs induced cell motility in a concentration-dependent manner. An EGFR kinase inhibitor (AG494) or a PI3 kinase inhibitor (LY294002) inhibited cell migration and reduced 11,12-EET-induced cell migration. Importantly, synthetic EET antagonists (14,15-EEZE, 14,15-EEZE-PEG and 14,15-EEZE-mSI) inhibited EET-induced cell invasion and migration. 11,12-EET induced cell stretching and myosin-actin microfilament formation as well as increased phosphorylation of EGFR and Akt (Ser473) while 14,15-EEZE inhibited these effects. These results suggest that EETs induce and EET antagonists inhibit cell motility, possibly by putative EET receptor-mediated EGFR and PI3K/Akt pathways, and suggest EET antagonists as potential therapeutic agents for prostate cancer.

Nithipatikom, Kasem; Brody, Daniel M.; Tang, Alan T.; Manthati, Vijaya L.; Falck, John R.; Williams, Carol L.; Campbell, William B.

2012-01-01

315

Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumour activity  

PubMed Central

All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer of differentiation. However, the clinical use of all-trans-retinoic acid in the treatment of cancer is significantly hampered by its toxicity and the prompt emergence of resistance, believed to be caused by increased all-trans-retinoic acid metabolism. Inhibitors of all-trans-retinoic acid metabolism may therefore prove valuable in the treatment of cancer. In this study, we characterize R116010 as a new anticancer drug that is a potent inhibitor of all-trans-retinoic acid metabolism. In vitro, R116010 potently inhibits all-trans-retinoic acid metabolism in intact T47D cells with an IC50-value of 8.7?nM. In addition, R116010 is a selective inhibitor as indicated by its inhibition profile for several other cytochrome P450-mediated reactions. In T47D cell proliferation assays, R116010 by itself has no effect on cell proliferation. However, in combination with all-trans-retinoic acid, R116010 enhances the all-trans-retinoic acid-mediated antiproliferative activity in a concentration-dependent manner. In vivo, the growth of murine oestrogen-independent TA3-Ha mammary tumours is significantly inhibited by R116010 at doses as low as 0.16?mg?kg?1. In conclusion, R116010 is a highly potent and selective inhibitor of all-trans-retinoic acid metabolism, which is able to enhance the biological activity of all-trans-retinoic acid, thereby exhibiting antitumour activity. R116010 represents a novel and promising anticancer drug with an unique mechanism of action. British Journal of Cancer (2002) 86, 605–611. DOI: 10.1038/sj/bjc/6600056 www.bjcancer.com © 2002 Cancer Research UK

Van heusden, J; Van Ginckel, R; Bruwiere, H; Moelans, P; Janssen, B; Floren, W; van der Leede, B J; van Dun, J; Sanz, G; Venet, M; Dillen, L; Van Hove, C; Willemsens, G; Janicot, M; Wouters, W

2002-01-01

316

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

Microsoft Academic Search

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

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

2000-01-01

317

Semisynthetic ursolic acid fluorolactone derivatives inhibit growth with induction of p21(waf1) and induce apoptosis with upregulation of NOXA and downregulation of c-FLIP in cancer cells.  

PubMed

A series of ursolic acid ((1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid) derivatives with a 12-fluoro-13,28?-lactone moiety were synthesized using the electrophilic fluorination reagent Selectfluor. The antiproliferative effects of these novel compounds were evaluated in AsPC-1 pancreatic cancer cells, and the structure-activity relationships (SARs) were evaluated. Of the compounds synthesized, ursolic acid derivatives carrying a heterocyclic ring, such as imidazole or methylimidazole, and cyanoenones were among the more potent inhibitors of AsPC-1 pancreatic cancer cell growth. 2-Cyano-3-oxo-12?-fluoro-urs-1-en-13,28?-olide, compound 20, was the most effective inhibitor with IC(50) values of 0.7, 0.9 and 1.8 ?M in pancreatic cancer cell lines AsPC-1, MIA PaCa-2 and PANC-1, respectively. This compound also exhibited better antiproliferative activities against breast (MCF7), prostate (PC-3), hepatocellular (Hep G2) and lung (A549) cancer cell lines, with IC(50) values lower than 1 ?M. The mechanism of action by which these compounds exert their biological effect was evaluated in AsPC-1 cells using the most potent inhibitor synthesized, compound 20. At 1 ?M, the cell cycle arrested at the G1 phase with upregulation of p21(waf1). Apoptosis was induced at an inhibitor concentration of 8 ?M with upregulation of NOXA and downregulation of c-FLIP. These data indicate that fluorolactone derivatives of ursolic acid have improved antiproliferative activity, acting through arrest of the cell cycle and induction of apoptosis. PMID:22807348

Leal, Ana S; Wang, Rui; Salvador, Jorge A R; Jing, Yongkui

2012-07-16

318

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

SciTech Connect

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

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

1986-05-01

319

Kinetic model of particle-inhibited grain growth  

NASA Astrophysics Data System (ADS)

The effects of second phase particles on matrix grain growth kinetics were investigated using Al2O3-SiC as a model system. In particular, the validity of the conclusion drawn from a previous kinetic analysis that the kinetics of particle-inhibited grain growth in Al2 O3-SiC samples with an intermediate volume fraction of second phase could be well quantified by a modified-Zener model was investigated. A critical analysis of assumptions made during the previous kinetic analysis revealed oversimplifications which affect the validity of the conclusion. Specifically, the degree of interaction between particles and grain boundaries was assumed to be independent of the mean second phase particle size and size distribution. In contrast, current measurements indicate that the degree of interaction in Al2O3-SiC is dependent on these parameters. An improved kinetic model for particle-inhibited grain growth in Al 2O3-SiC was developed using a modified-Zener approach. The comparison of model predictions with experimental grain growth data indicated that significant discrepancies (as much as 4--5 orders of magnitude) existed. Based on this, it was concluded that particles had a much more significant effect on grain growth kinetics than that caused by a simple reduction of the boundary driving force due to the removal of boundary area. Consequently, it was also concluded that the conclusion drawn from the earlier kinetic analysis regarding the validity of a modified-Zener model was incorrect. Discrepancies between model and experiment were found to be the result of a significant decrease in experimental growth rate constant not predicted by the model. Possible physical mechanisms for such a decrease were investigated. The investigation of a small amount of SiO2 on grain growth in Al2O3 indicated that the decrease was not the result of a decrease in grain boundary mobility due to impurity contamination by particles. By process of elimination and based on previous observations made in 2-D and 3-D Monte Carlo-Potts Model simulations, it was concluded that the decrease in growth rate constant was most likely due to the removal of grain boundary curvature by particles.

Thompson, Gary Scott

320

HE3235 inhibits growth of castration-resistant prostate cancer.  

PubMed

Treatments for advanced prostate cancer (CaP) typically involve androgen deprivation therapy. However, most patients eventually develop castration-resistant CaP (CRPC) for which highly effective therapies are limited. We explored the efficacy of a novel agent, HE3235, in inhibiting growth of CRPC in preclinical models. Castrated male mice were implanted subcutaneously with LuCaP35V CaP xenografts in the presence and absence of 5'-androstenediol (AED) and treated with HE3235. To investigate the effect of HE3235 on CaP tumor in the bone, castrated mice were injected intratibially with C4-2B CaP cells and treated with HE3235. Serum prostate-specific antigen (PSA) levels, tumor volume, immunohistochemistry, gene expression, and levels of intratumoral androgens were analyzed. HE3235 significantly prolonged the tumor doubling time of LuCaP35V, decreased androgen receptor expression, and lowered levels of intratumoral testosterone by approximately 89% and dihydrotestosterone by approximately 63% in both the presence and the absence of AED. HE3235 inhibited tumor growth in the bone environment. Weights of tumored tibiae of HE3235-treated animals were lower than those of control (P = .031), and normalized PSA levels were also significantly decreased at the end of study by HE3235 treatment (P = .0076). HE3235 inhibits the growth of subcutaneous CRPC as well as CRPC in the bone environment. Our data show that HE3235 exhibits a wide range of effects, including alteration of androgen receptor signaling and reductions in levels of intratumoral androgens. Our results support ongoing clinical investigations into the effectiveness of HE3235 in the setting of CRPC and warrants further studies into the mechanisms behind the effects of HE3235. PMID:19881957

Koreckij, Theodore D; Trauger, Richard J; Montgomery, Robert Bruce; Pitts, Tiffany E M; Coleman, Ilsa; Nguyen, Holly; Reading, Chris L; Nelson, Peter S; Vessella, Robert L; Corey, Eva

2009-11-01

321

Osmotic Shock Inhibits Auxin-stimulated Acidification and Growth.  

PubMed

Cells of oat coleoptiles (Avena sativa L. cv. "Garry") have been osmotically shocked in order to observe the effect of alterations of the plasma membrane on some auxin responses. When coleoptile sections were treated sequentially with 0.5 m mannitol and 1 mm Na-phosphate (pH 6.4) at 4 C, polar auxin transport and acidification by 1 mM CaCl(2) were unaffected, but auxin-stimulated acidification and growth were eliminated. Shock treatment also had no effect on acid-stimulated growth or on freezing point depression by the cytoplasm. It is suggested that osmotic shock modifies a portion of the plasma membrane which interacts with auxin and eventually leads to growth. PMID:16659853

Rubinstein, B

1977-03-01

322

Acid mine drainage attenuation by inhibition of pyrite bioleaching using limestone and olive pomace  

Microsoft Academic Search

The control and inhibition of pyrite bioleaching involved in the generation of acid mine drainage was studied. Inhibition of pyrite bioleaching was performed by varying the pyrite concentration in the medium (substrate inhibition) and\\/or by addition of limestone (inhibition by pH increase) and olive pomace (inhibition by organic compounds). Inhibition tests of pyrite bioleaching were performed according to a full

F. Pagnanelli; C. Cruz Viggi; L. Toro

2012-01-01

323

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

PubMed

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

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

2012-01-30

324

Inhibition of Low pH-induced Elongation in Avena Coleoptiles by Abscisic Acid.  

PubMed

An angular position-sensing transducer was used to make continuous measurements of acid-induced elongation of Avena sativa coleoptile segments. Elongation rates at pH 4.5 (5 mm succinate buffer) were about 5-fold greater than those at pH 6.0. Buffered 0.1 mm abscisic acid produced a partial decrease of the growth rate. Pretreatments with abscisic acid buffered at pH 6.0 usually caused a further reduction of the elongation response when the coleoptile segments were subsequently placed in buffer at pH 4.5 containing abscisic acid. Abscisic acid did not completely prevent the pH effect in any of these experiments, and the brief latent period of the pH response was not affected by abscisic acid treatments. At pH 4.5, where the inhibitory effect of ABA was maximum, low pH-induced elongation was also inhibited by KCN and HgCl(2). These results suggest that pH-(4.5) induced elongation in this system may be dependent on some metabolic processes and that abscisic acid-induced inhibition of this elongation may involve an interaction with these processes. PMID:16658443

Rehm, M M; Cline, M G

1973-05-01

325

Angiopoietin-2 inhibits the growth of tongue carcinoma without affecting expression of vascular endothelial growth factor.  

PubMed

Angiopoietin-2 (Ang-2) has been identified as an important factor in tumour angiogenesis through its action in blocking the stabilizing actions of Ang-2 and leading to new tumour vessel growth in the presence of vascular endothelial growth factor (VEGF). In the authors' previous study, over-expression of Ang-2 in Tca8113 tongue tumour cells inhibited growth. The current study aims to clarify the mechanisms of Ang-2-mediated tumour growth inhibition and its role in the regulation of VEGF expression. These studies used tumours derived from Ang-2-transfected Tca8113 cells injected into nude mice. The results showed that Ang-2-transfected tumours displayed aberrant angiogenic vessels with few associated smooth muscle cells. No detectable differences in VEGF expression were observed between Ang-2-transfected and parental tumours. Tumours produced by the Ang-2 transfection also had a higher apoptosis index and lower tumour cell proliferative index than tumours in the control groups. These observations suggest that enhanced expression of Ang-2 has no effect on VEGF expression and results in tumour vessel regression and inhibition of tumour growth. PMID:21163623

Chen, H-h; Chai, L; Wang, S-q; Shi, Z-j; Wu, Q-l

2010-12-15

326

Cellular growth inhibition by TGF-beta1 involves IRS proteins.  

PubMed

In Mv1Lu cells, insulin partially reverses transforming growth factor-beta1 (TGF-beta1) growth inhibition in the presence of alpha5beta1 integrin antagonists. TGF-beta1 appears to induce phosphorylation of IRS-2 in these cells; this is inhibited by a TGF-beta antagonist known to reverse TGF-beta growth inhibition. Stable transfection of 32D myeloid cells (which lack endogenous IRS proteins and are insensitive to growth inhibition by TGF-beta1) with IRS-1 or IRS-2 cDNA confers sensitivity to growth inhibition by TGF-beta1; this IRS-mediated growth inhibition can be partially reversed by insulin in 32D cells stably expressing IRS-2 and the insulin receptor (IR). These results suggest that growth inhibition by TGF-beta1 involves IRS proteins. PMID:15135063

Huang, Shuan Shian; Leal, Sandra M; Chen, Chun-Lin; Liu, I-Hua; Huang, Jung San

2004-05-01

327

Dynamic adaption of metabolic pathways during germination and growth of lily pollen tubes after inhibition of the electron transport chain.  

PubMed

Investigation of the metabolome and the transcriptome of pollen of lily (Lilium longiflorum) gave a comprehensive overview of metabolic pathways active during pollen germination and tube growth. More than 100 different metabolites were determined simultaneously by gas chromatography coupled to mass spectrometry, and expressed genes of selected metabolic pathways were identified by next-generation sequencing of lily pollen transcripts. The time-dependent changes in metabolite abundances, as well as the changes after inhibition of the mitochondrial electron transport chain, revealed a fast and dynamic adaption of the metabolic pathways in the range of minutes. The metabolic state prior to pollen germination differed clearly from the metabolic state during pollen tube growth, as indicated by principal component analysis of all detected metabolites and by detailed observation of individual metabolites. For instance, the amount of sucrose increased during the first 60 minutes of pollen culture but decreased during tube growth, while glucose and fructose showed the opposite behavior. Glycolysis, tricarbonic acid cycle, glyoxylate cycle, starch, and fatty acid degradation were activated, providing energy during pollen germination and tube growth. Inhibition of the mitochondrial electron transport chain by antimycin A resulted in an immediate production of ethanol and a fast rearrangement of metabolic pathways, which correlated with changes in the amounts of the majority of identified metabolites, e.g. a rapid increase in ?-aminobutyric acid indicated the activation of a ?-aminobutyric acid shunt in the tricarbonic acid cycle, while ethanol fermentation compensated the reduced ATP production after inhibition of the oxidative phosphorylation. PMID:23660836

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

2013-05-09

328

Inhibition of fatty acid synthase prevents preadipocyte differentiation  

Microsoft Academic Search

Inhibition of fatty acid synthase (FAS) reduces food intake in rodents. As adipose tissue expresses FAS, we sought to investigate the effect of reduced FAS activity on adipocyte differentiation. FAS activity was suppressed either pharmacologically or by siRNA during differentiation of 3T3-L1 cells. Cerulenin (10?M), triclosan (50?M), and C75 (50?M) reduced dramatically visible lipid droplet accumulation, while incorporation of [1-14C]acetate

Bernhard Schmid; Jörg F. Rippmann; Moh Tadayyon; Bradford S. Hamilton

2005-01-01

329

Praziquantel Synergistically Enhances Paclitaxel Efficacy to Inhibit Cancer Cell Growth  

PubMed Central

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.

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

2012-01-01

330

Cesium Inhibits Plant Growth through Jasmonate Signaling in Arabidopsis thaliana  

PubMed Central

It has been suggested that cesium is absorbed from the soil through potassium uptake machineries in plants; however, not much is known about perception mechanism and downstream response. Here, we report that the jasmonate pathway is required in plant response to cesium. Jasmonate biosynthesis mutant aos and jasmonate-insensitive mutant coi1-16 show clear resistance to root growth inhibition caused by cesium. However, the potassium and cesium contents in these mutants are comparable to wild-type plants, indicating that jasmonate biosynthesis and signaling are not involved in cesium uptake, but involved in cesium perception. Cesium induces expression of a high-affinity potassium transporter gene HAK5 and reduces potassium content in the plant body, suggesting a competitive nature of potassium and cesium uptake in plants. It has also been found that cesium-induced HAK5 expression is antagonized by exogenous application of methyl-jasmonate. Taken together, it has been indicated that cesium inhibits plant growth via induction of the jasmonate pathway and likely modifies potassium uptake machineries.

Adams, Eri; Abdollahi, Parisa; Shin, Ryoung

2013-01-01

331

Excentric cleavage products of beta-carotene inhibit estrogen receptor positive and negative breast tumor cell growth in vitro and inhibit activator protein-1-mediated transcriptional activation.  

PubMed

Both retinoids and carotenoids are potentially useful chemopreventive agents. In this study we tested the effect of synthetic excentric cleavage products of beta-carotene on the growth of the MCF-7, Hs578T and MDA-MB-231 human breast cancer cells. The apo-beta-carotenoic acids (beta-apo-CA) beta-apo-14'-, beta-apo-12'-, beta-apo-10'- and beta-apo-8'-CA are structurally similar to all-trans-retinoic acid (atRA) but have different side chain lengths. Nine days of treatment with atRA inhibited MCF-7 and Hs578T cell proliferation in a dose-dependent manner. beta-apo-14'-CA and beta-apo-12'-CA significantly inhibited MCF-7 growth, whereas only beta-apo-14'-CA inhibited Hs578T growth. None of these treatments inhibited the growth of MDA-MB-231 cells. Potential mechanisms of growth inhibition, i.e., regulation of the cell cycle control proteins E2F1 and retinoblastoma protein (RB), and effect on activator protein-1 (AP-1)-mediated gene regulation were examined. beta-apo-14'-CA and atRA inhibited the expression of E2F1 protein in MCF-7 and Hs578T cells. beta-apo-14'-CA, beta-apo-12'-CA and atRA down-regulated RB protein expression in MCF-7 but not in Hs578T cells. The effect of phorbol ester-induced transcriptional activation of a collagenase promoter-reporter gene construct was strongly inhibited by 1 micromol/L beta-apo-14'-CA, atRA (MCF-7, Hs578T) or beta-apo-12'-CA (MCF-7). These effects were due neither to cellular conversion of beta-apo-CA to atRA nor to high affinity binding to the retinoid acid receptors. Thus, beta-apo-CAs were effective inhibitors of breast tumor cell proliferation, possibly mediated through down-regulation of cell cycle regulatory proteins and/or inhibition of AP-1 transcriptional activity. The ability of beta-apo-CA to regulate breast tumor cell growth independently of conversion to atRA suggests that these compounds may have fewer side effects than retinoids and, therefore, have a potential chemotherapeutic value that deserves further examination. PMID:12042460

Tibaduiza, Elmi C; Fleet, James C; Russell, Robert M; Krinsky, Norman I

2002-06-01

332

Growth inhibition by hexoses of a temperature-sensitive thiazoleless mutant of Salmonella typhimurium.  

PubMed

A Salmonella typhimurium mutant showing impairment in the utilization of hexoses was isolated after treatment with N-methyl-N'-nitro-N-nitrosoguanidine. At 30 C, it grew with hexoses (glucose, fructose, galactose, mannitol), glycerol, succinate, or acid-hydrolyzed casein. At 37 C, it failed to grow with any of the hexoses. Enzymatic determinations demonstrated, however, that the enzymes of the glycolytic pathway (up to the formation of triose phosphates) were present and active at 25 and 32 C. At 42 C, the mutant did not grow with any of the carbon sources used. At both 37 and 42 C, the mutant grew perfectly well with hexoses if yeast extract was present. The metabolite required for growth was thiamine or, specifically, its thiazole moiety. If glucose was added to a culture growing in glycerol, at 37 C, growth was inhibited. This inhibition was relieved by the addition of thiamine or thiazole. Thus, at 37 C and only in the presence of hexoses, the mutant manifests a requirement for thiazole. This auxotrophy is absolute at 42 C. These data indicate that, in this mutant, some derivative of hexoses inhibits the synthesis of thiazole, and that this inhibition is also dependent on the temperature of incubation. The position in the bacterial chromosome of the genetic locus of this lesion (thz(-)) was determined by conjugation and found to coincide with the only thiamine (thi) locus so far reported. PMID:5340682

Parada, J L; Ortega, M V

1967-09-01

333

Lactic acid bacteria – Potential for control of mould growth and mycotoxins: A review  

Microsoft Academic Search

Most data dealing with the biopreservative activity of lactic acid bacteria (LAB) are focused on their antibacterial effects. Food spoilage by mould and the occurrence of their mycotoxins constitute a potential health hazard. Development of biological control should help improve the safety of products by controlling mycotoxin contamination. Data have actually shown that many LAB can inhibit mould growth and

D. K. D. Dalié; A. M. Deschamps; F. Richard-Forget

2010-01-01

334

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

PubMed Central

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

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

2007-01-01

335

Mirtazapine Inhibits Tumor Growth via Immune Response and Serotonergic System  

PubMed Central

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.

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

336

Evidence that iodolactones are the mediators of growth inhibition by iodine on the thyroid.  

PubMed

Different iodolipids have been identified within the last decades in thyroid cells exposed to iodine in vitro as well as in vivo. Iodolipids have been supposed to be involved in thyroid autoregulation, but no specific compounds could be found. A new approach was stimulated by the finding that rat thyroid lobes were able to iodinate arachidonic acid and docosahexaenoic acids in vitro. Meanwhile 6-iodo-5 hydroxy-eicosatrienoic acid (delta-iodolactone) has been identified in human thyroid tissue, but only after treating the patients with high doses of iodine before thyroidectomy, whereas in untreated endemic goiter this delta-iodolactone could not be found. In rats treated with iodolactones, methimazole induced goiter formation could be prevented. In human and porcine thyroid cells in vitro, delta-iodolactone inhibited epidermal growth factor (EGF) induced proliferation in 50-fold lower concentrations than iodide itself. Furthermore it could be demonstrated that only the IP3-, but not the cAMP generation in porcine thyroid cells could be inhibited by this compound. Also a structure specifity for delta-iodolactones for the biological activity could be shown. We will summarize and discuss these important new findings on the role of iodolactones on thyroid growth. PMID:8767514

Gärtner, R; Dugrillon, A; Bechtner, G

1996-01-01

337

Inhibition of cell growth by a hypothalamic peptide.  

PubMed Central

A fraction purified from acetic acid extracts of porcine hypothalami was found to contain significant antimitogenic activity when tested in normal and neoplastic cell lines. Addition of this hypothalamic material (1-100 micrograms/ml) to culture media significantly inhibited [3H]thymidine incorporation into cellular DNA in several cell lines. Amino acid incorporation into pituitary proteins and uridine incorporation into RNA were also significantly reduced by this factor(s). Addition to the culture media of this hypothalamic material at 5 micrograms/ml and 50 micrograms/ml per day decreased by 17% and 36%, respectively, cell numbers of 3T6 fibroblast cell cultures. Time-response curves showed that the inhibition of [3H]thymidine incorporation into DNA in 3T6 fibroblast cells begins within 2 hr after adding this fraction to the culture medium. The inhibitory action cannot be explained by a direct cytotoxic effect since 3T6 cells labeled with 51Cr and incubated for 6 hr in the presence of this hypothalamic fraction fail to show an increase in the release of 51Cr into the medium as compared with controls. Incubation with trypsin and chymotrypsin completely abolished the antimitogenic activity of this material and pepsin decreased it. This strongly suggests that the antimitogenic activity exhibited by this fraction is due to a polypeptide(s). These observations provide evidence for the presence in the mammalian hypothalamus of an antimitogenic peptide(s) that may be involved in the regulation of cell proliferation.

Redding, T W; Schally, A V

1982-01-01

338

Fibroblast Growth Factor 21 (FGF21) Inhibits Chondrocyte Function and Growth Hormone Action Directly at the Growth Plate  

PubMed Central

Fibroblast growth factor 21 (FGF21) modulates glucose and lipid metabolism during fasting. In addition, previous evidence indicates that increased expression of FGF21 during chronic food restriction is associated with reduced bone growth and growth hormone (GH) insensitivity. In light of the inhibitory effects on growth plate chondrogenesis mediated by other FGFs, we hypothesized that FGF21 causes growth inhibition by acting directly at the long bones' growth plate. We first demonstrated the expression of FGF21, FGFR1 and FGFR3 (two receptors known to be activated by FGF21) and ?-klotho (a co-receptor required for the FGF21-mediated receptor binding and activation) in fetal and 3-week-old mouse growth plate chondrocytes. We then cultured mouse growth plate chondrocytes in the presence of graded concentrations of rhFGF21 (0.01–10 ?g/ml). Higher concentrations of FGF21 (5 and 10 ?g/ml) inhibited chondrocyte thymidine incorporation and collagen X mRNA expression. 10 ng/ml GH stimulated chondrocyte thymidine incorporation and collagen X mRNA expression, with both effects prevented by the addition in the culture medium of FGF21 in a concentration-dependent manner. In addition, FGF21 reduced GH binding in cultured chondrocytes. In cells transfected with FGFR1 siRNA or ERK 1 siRNA, the antagonistic effects of FGF21 on GH action were all prevented, supporting a specific effect of this growth factor in chondrocytes. Our findings suggest that increased expression of FGF21 during food restriction causes growth attenuation by antagonizing the GH stimulatory effects on chondrogenesis directly at the growth plate. In addition, high concentrations of FGF21 may directly suppress growth plate chondrocyte proliferation and differentiation.

Wu, Shufang; Levenson, Amy; Kharitonenkov, Alexei; De Luca, Francesco

2012-01-01

339

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

PubMed

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

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

2013-01-24

340

Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancer.  

PubMed

The fibroblast growth factor (FGF) pathway promotes tumor growth and angiogenesis in many solid tumors. Although there has long been interest in FGF pathway inhibitors, development has been complicated: An effective FGF inhibitor must block the activity of multiple mitogenic FGF ligands but must spare the metabolic hormone FGFs (FGF-19, FGF-21, and FGF-23) to avoid unacceptable toxicity. To achieve these design requirements, we engineered a soluble FGF receptor 1 Fc fusion protein, FP-1039. FP-1039 binds tightly to all of the mitogenic FGF ligands, inhibits FGF-stimulated cell proliferation in vitro, blocks FGF- and vascular endothelial growth factor (VEGF)-induced angiogenesis in vivo, and inhibits in vivo growth of a broad range of tumor types. FP-1039 antitumor response is positively correlated with RNA levels of FGF2, FGF18, FGFR1c, FGFR3c, and ETV4; models with genetic aberrations in the FGF pathway, including FGFR1-amplified lung cancer and FGFR2-mutated endometrial cancer, are particularly sensitive to FP-1039-mediated tumor inhibition. FP-1039 does not appreciably bind the hormonal FGFs, because these ligands require a cell surface co-receptor, klotho or ?-klotho, for high-affinity binding and signaling. Serum calcium and phosphate levels, which are regulated by FGF-23, are not altered by administration of FP-1039. By selectively blocking nonhormonal FGFs, FP-1039 treatment confers antitumor efficacy without the toxicities associated with other FGF pathway inhibitors. PMID:23536011

Harding, Thomas C; Long, Li; Palencia, Servando; Zhang, Hongbing; Sadra, Ali; Hestir, Kevin; Patil, Namrata; Levin, Anita; Hsu, Amy W; Charych, Deborah; Brennan, Thomas; Zanghi, James; Halenbeck, Robert; Marshall, Shannon A; Qin, Minmin; Doberstein, Stephen K; Hollenbaugh, Diane; Kavanaugh, W Michael; Williams, Lewis T; Baker, Kevin P

2013-03-27

341

Cytostatic inhibition of cancer cell growth by lignan secoisolariciresinol diglucoside.  

PubMed

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

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

2010-11-01

342

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

PubMed Central

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

Wimmel, A; Wiedenmann, B; Rosewicz, S

2003-01-01

343

Opioid growth factor - opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer.  

PubMed

Triple negative breast cancer (TNBC) represents approximately 15% of the newly diagnosed cancers worldwide and is characterized by tissue lacking in estrogen, progesterone and human epidermal growth factor receptors. TNBC disproportionately affects younger women and women of colour, and new treatments are needed. The opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis is a determinant of cell proliferation in neoplasia, and OGF is an endogenously produced pentapeptide that inhibits cell replication by interacting with OGFr and upregulating cyclin-dependent inhibitory kinase pathways thus reducing DNA synthesis. In these studies we investigated the presence and function of the OGF-OGFr axis in two human TNBC cell lines, as well as in breast cancer cell lines containing hormonal receptors. TNBC cell lines MDA-MD-231 and BT-20, as well as human breast cancer cells SK-BR-3 and MCF-7, were examined for the presence of pentapeptide and receptors, as well as their response to OGF. Specificity of peptide and receptor was confirmed by antibody neutralization and molecular studies to knockdown classical receptor protein. The requirement for protein transcription and translation and RNA transcription were investigated. Growth of TNBC cells in the presence of OGF and standard of care chemotherapeutic agent paclitaxel was evaluated to determine both efficacy and protective effects against toxicity. OGF treatment inhibited TNBC cells in a dosage related, receptor mediated, and reversible manner. OGF was the specific endogenous opioid to inhibit cell proliferation, and this was mediated by p21 cyclin dependent inhibitory kinase pathways, and required protein and RNA synthesis. OGFr was the specific receptor involved; both peptide and receptor were detected in all four cell lines. OGF treatment inhibited growth of all cancer cell lines evaluated, and reduced cell death in cultures exposed to paclitaxel. The OGF-OGFr axis is present and functioning in TNBC cell lines, and provides a novel biological pathway as potential therapy. PMID:23918871

Zagon, Ian S; Porterfield, Nancy K; McLaughlin, Patricia J

2013-06-01

344

Effect of Acetic Acid on Growth and Ethanol Fermentation of Xylose Fermenting Yeast and Saccharomyces cerevisiae  

Microsoft Academic Search

Growth of some xylose fermenting yeasts, Candida shehatae, Pichia stipitis CBS5773, fusant F101 and fusant F198, was completely inhibited in xylose medium added with 0.5% v\\/v acetic acid which caused the reduction of pH to 4.1. Only one xylose fermenting strain, Pachysolen tannophilus NRRL-Y2460, showed relatively low growth and ethanol fermentation. However, in the medium added with 1.0% v\\/v acetic

Savitree Limtong; Tawatchai Sumpradit; Vichien Kitpreechavanich; Manee Tuntirungkij; Tatsuji Seki; Toshiomi Yoshida

345

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

PubMed

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

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

2008-02-01

346

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

NASA Astrophysics Data System (ADS)

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

Li, Yunlong; Xing, Da

2007-05-01

347

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

PubMed

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

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

2012-07-24

348

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

Microsoft Academic Search

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

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

1984-01-01

349

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

Microsoft Academic Search

  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

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

1997-01-01

350

Linoleic acid suppresses colorectal cancer cell growth by inducing oxidant stress and mitochondrial dysfunction  

Microsoft Academic Search

Some polyunsaturated fatty acids (PUFAs), if not all, have been shown to have tumoricidal action, but their exact mechanism(s) of action is not clear. In the present study, we observed that n-6 PUFA linoleic acid (LA) inhibited tumor cell growth at high concentrations (above 300 ?M); while low concentrations (100-200 ?M) promoted proliferation. Analysis of cell mitochondrial membrane potential, reactive

Xiaofeng Lu; Haining Yu; Qi Ma; Shengrong Shen; Undurti N Das

2010-01-01

351

Omega-3 Fatty Acids and a Novel Mammary Derived Growth Inhibitor Fatty Acid Binding Protein MRG in Suppression of Mammary Tumor.  

National Technical Information Service (NTIS)

We have previously identified and characterized a novel tumor growth inhibitor and a fatty acid binding protein in human mammary gland and named it as Mammary derived growth inhibitor Related Gene MRG. MRG has tumor-suppressing activities; it inhibits bre...

Y. Liu

2001-01-01

352

Ambuic Acid Inhibits the Biosynthesis of Cyclic Peptide Quormones in Gram-Positive Bacteria ?  

PubMed Central

Quorum sensing is a cell-density-dependent regulatory system in gram-positive bacteria and is often regulated by cyclic peptides called “quormones,” which function as extracellular communication signals. With an aim to discover an antipathogenic agent targeting quorum sensing in gram-positive bacteria, we screened 153 samples of fungal butanol extracts with the guidance of the inhibition of quorum-sensing-mediated gelatinase production in Enterococcus faecalis. Following the screenings, we found that ambuic acid, a known secondary fungal metabolite, inhibited the quorum-sensing-mediated gelatinase production without influencing the growth of E. faecalis. We further demonstrated that ambuic acid targeted the biosynthesis of a cyclic peptide quormone called gelatinase biosynthesis-activating pheromone. Furthermore, ambuic acid also inhibited the biosynthesis of the cyclic peptide quormones of Staphylococcus aureus and Listeria innocua. These results suggest the potential use of ambuic acid as a lead compound of antipathogenic drugs that target the quorum-sensing-mediated virulence expression of gram-positive bacteria.

Nakayama, Jiro; Uemura, Yumi; Nishiguchi, Kenzo; Yoshimura, Norito; Igarashi, Yasuhiro; Sonomoto, Kenji

2009-01-01

353

Loss of growth inhibitory effects of retinoic acid in human breast cancer cells following long-term exposure to retinoic acid.  

PubMed

Although retinoids are known to be inhibitory to breast cancer cell growth, a key remaining question is whether they would remain effective if administered long-term. We describe here the long-term effects of all- trans retinoic acid on two oestrogen-dependent human breast cancer cell lines MCF7 and ZR-75-1. Although both cell lines were growth inhibited by retinoic acid in the short-term in either the absence or the presence of oestradiol, prolonged culture with 1 microM all- trans retinoic acid resulted in the cells acquiring resistance to the growth inhibitory effects of retinoic acid. Time courses showed that oestrogen deprivation of the cell lines resulted in upregulation of the basal non-oestrogen stimulated growth rate such that cells learned to grow at the same rate without as with oestradiol, but the cells remained growth inhibited by retinoic acid throughout. Addition of 1 microM all- trans retinoic acid to steroid deprivation conditions resulted in reproducible loss of growth response to both retinoic acid and oestradiol, although the time courses were separable in that loss of growth response to retinoic acid preceded that of oestradiol. Loss of growth response to retinoic acid did not involve loss of receptors, ER as measured by steroid binding assay or RARalpha as measured by Northern blotting. Function of the receptors was retained in terms of the ability of both oestradiol and retinoic acid to upregulate pS2 gene expression, but there was reduced ability to upregulate transiently transfected ERE- and RRE-linked reporter genes. Despite the accepted role of IGFBP3 in retinoic acid-mediated growth inhibition, progression to retinoic acid resistance occurred irrespective of level of IGFBP3, which remained high in the resistant MCF7 cells. Measurement of AP1 activity showed that the two cell lines had markedly different basal AP1 activities, but that progression to resistance was accompanied in both cases by a lost ability of retinoic acid to reduce AP1 activity. These results warn of potential resistance which could arise on long-term treatment with retinoic acid in a clinical situation and echo the problems of progression to endocrine resistance. It seems that whatever the constraints imposed on growth, these cells have a remarkable ability to escape from growth inhibition. However, the ability of retinoic acid to delay progression to oestrogen resistance is encouraging for endocrine therapy, and the concentration-dependence of retinoic acid resistance suggests that progression is not absolute but could be manipulated by dose. PMID:11027432

Stephen, R; Darbre, P D

2000-11-01

354

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

Microsoft Academic Search

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

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

2006-01-01

355

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

Microsoft Academic Search

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

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

2000-01-01

356

Blocking Fibroblast Growth Factor Receptor Signaling Inhibits Tumor Growth, Lymphangiogenesis, and Metastasis  

PubMed Central

Fibroblast Growth Factor receptor (FGFR) activity plays crucial roles in tumor growth and patient survival. However, FGF (Fibroblast Growth Factor) signaling as a target for cancer therapy has been under-investigated compared to other receptor tyrosine kinases. Here, we studied the effect of FGFR signaling inhibition on tumor growth, metastasis and lymphangiogenesis by expressing a dominant negative FGFR (FGFR-2DN) in an orthotopic mouse mammary 66c14 carcinoma model. We show that FGFR-2DN-expressing 66c14 cells proliferate in vitro slower than controls. 66c14 tumor outgrowth and lung metastatic foci are reduced in mice implanted with FGFR-2DN-expressing cells, which also exhibited better overall survival. We found 66c14 cells in the lumen of tumor lymphatic vessels and in lymph nodes. FGFR-2DN-expressing tumors exhibited a decrease in VEGFR-3 (Vascular Endothelial Growth Factor Receptor-3) or podoplanin-positive lymphatic vessels, an increase in isolated intratumoral lymphatic endothelial cells and a reduction in VEGF-C (Vascular Endothelial Growth Factor-C) mRNA expression. FGFs may act in an autocrine manner as the inhibition of FGFR signaling in tumor cells suppresses VEGF-C expression in a COX-2 (cyclooxygenase-2) or HIF1-? (hypoxia-inducible factor-1 ?) independent manner. FGFs may also act in a paracrine manner on tumor lymphatics by inducing expression of pro-lymphangiogenic molecules such as VEGFR-3, integrin ?9, prox1 and netrin-1. Finally, in vitro lymphangiogenesis is impeded in the presence of FGFR-2DN 66c14 cells. These data confirm that both FGF and VEGF signaling are necessary for the maintenance of vascular morphogenesis and provide evidence that targeting FGFR signaling may be an interesting approach to inhibit tumor lymphangiogenesis and metastatic spread.

Larrieu-Lahargue, Frederic; Welm, Alana L.; Bouchecareilh, Marion; Alitalo, Kari; Li, Dean Y.; Bikfalvi, Andreas; Auguste, Patrick

2012-01-01

357

Cadmium inhibits acid secretion in stimulated frog gastric mucosa  

SciTech Connect

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

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

2010-06-01

358

Tranexamic acid concentrations associated with human seizures inhibit glycine receptors  

PubMed Central

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

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

2012-01-01

359

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

PubMed Central

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.

Gregory, P C

1987-01-01

360

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

PubMed Central

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

2012-01-01

361

HDAC6 inhibition restores ciliary expression and decreases tumor growth.  

PubMed

Primary cilia are multisensory organelles recently found to be absent in some tumor cells, but the mechanisms of deciliation and the role of cilia in tumor biology remain unclear. Cholangiocytes, the epithelial cells lining the biliary tree, normally express primary cilia and their interaction with bile components regulates multiple processes, including proliferation and transport. Using cholangiocarcinoma as a model, we found that primary cilia are reduced in cholangiocarcinoma by a mechanism involving histone deacetylase 6 (HDAC6). The experimental deciliation of normal cholangiocyte cells increased the proliferation rate and induced anchorage-independent growth. Furthermore, deciliation induced the activation of mitogen-activated protein kinase and Hedgehog signaling, two important pathways involved in cholangiocarcinoma development. We found that HDAC6 is overexpressed in cholangiocarcinoma and overexpression of HDAC6 in normal cholangiocytes induced deciliation and increased both proliferation and anchorage-independent growth. To evaluate the effect of cilia restoration on tumor cells, we targeted HDAC6 by short hairpin RNA (shRNA) or by the pharmacologic inhibitor, tubastatin-A. Both approaches restored the expression of primary cilia in cholangiocarcinoma cell lines and decreased cell proliferation and anchorage-independent growth. The effects of tubastatin-A were abolished when cholangiocarcinoma cells were rendered unable to regenerate cilia by stable transfection of IFT88-shRNA. Finally, inhibition of HDAC6 by tubastatin-A also induced a significant decrease in tumor growth in a cholangiocarcinoma animal model. Our data support a key role for primary cilia in malignant transformation, provide a plausible mechanism for their involvement, and suggest that restoration of primary cilia in tumor cells by HDAC6 targeting may be a potential therapeutic approach for cholangiocarcinoma. PMID:23370327

Gradilone, Sergio A; Radtke, Brynn N; Bogert, Pamela S; Huang, Bing Q; Gajdos, Gabriella B; LaRusso, Nicholas F

2013-01-31

362

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

Microsoft Academic Search

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

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

1993-01-01

363

Epidermal growth factor receptor monoclonal antibodies inhibit the growth of lung cancer cell lines.  

PubMed

The ability of monoclonal antibody (MAb 108), an immunoglobulin G (IgG)2a against the epidermal growth factor receptor (EGF-R), to interact with lung cancer cell lines was investigated. 125I-EGF bound with high affinity to non-small-cell lung cancer (NSCLC) cells, and MAb 108 inhibited specific binding of nine NSCLC cell lines in a dose-dependent manner (IC50 = 0.3-3 micrograms per ml). 125I-MAb 108 bound with high affinity (kd = 2 nM) to a single class of sites (Bmax = 70,000 per cell) using NSCLC neuroendocrine cell line NCI-H460. Specific 125I-MAb 108 binding was inhibited with high affinity by MAb 108 but not by a control antibody IgG using large-cell carcinoma cell line NCI-H1299. 125I-MAb 108 binding was not internalized at 37 degrees C using NSCLC neuroendocrine cell line NCI-H460 and adenocarcinoma cell line NCI-H23. Also, 1 microgram per ml of MAb 108 but not of a control IgG inhibited the clonal growth of NCI-H23 and squamous cell carcinoma cell line NCI-H157 in vitro. Also, MAb 108 inhibited xenograft formation of cell lines NCI-H460, NCI-H157, and NCI-H727 in nude mice in vivo. After a palpable tumor had formed using NCI-H460 cells, injection of 100 micrograms of MAb 108 (intraperitoneally three times weekly) inhibited xenograft volume in nude mice by approximately 50%. These data suggest that MAb 108 may interact with EGF receptors on lung cancer cell lines and inhibit NSCLC proliferation. PMID:1327029

Lee, M; Draoui, M; Zia, F; Gazdar, A; Oie, H; Bepler, G; Bellot, F; Tarr, C; Kris, R; Moody, T W

1992-01-01

364

Brazilin inhibits growth and induces apoptosis in human glioblastoma cells.  

PubMed

Brazilin, isolated from the methanol extract of the heart wood of Caesalpinia sappan, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous system malignancy, has a very poor prognosis and lacks effective therapeutic interventions. We, therefore, investigated the effects of different concentrations of and different periods of exposure to brazilin on cell proliferation and apoptosis in the glioma U87 cell line. Cell proliferation was investigated by MTT assays and growth curve analysis, apoptosis was assessed by FACS analysis and western blot studies. Brazilin showed dose-dependent inhibition of cell proliferation and induction of apoptosis in glioma cells. It also increased the ratio of cleaved poly-(ADP)-ribose polymerase and decreased the expression of caspase-3 and caspase-7. PMID:23429418

Lee, Dae-Young; Lee, Mi-Kyoung; Kim, Geum-Soog; Noh, Hyung-Jun; Lee, Min-Ho

2013-02-21

365

Isthmin inhibits glioma growth through antiangiogenesis in vivo.  

PubMed

Among glioma treatment strategies, antiangiogenesis emerges as a meaningful and feasible treatment approach for inducing long-term survival. Isthmin is a gene highly expressed in the isthmus of the midbrain-hindbrain organizer in Xenopus, and has recently been identified as a novel angiogenesis inhibitor. However, the potential of isthmin on the glioma angiogenesis has not been well studied. In the present study, we demonstrated that the recombinant adenovirus isthmin (Ad-isthmin) could inhibit VEGF-stimulated endothelial cell proliferation and induce apoptosis through a caspase-dependent pathway. In addition, Ad-isthmin significantly suppressed glioma growth through antiangiogenesis without apparent side effects. Taken together, our results demonstrated that isthmin could act as a novel angiogenesis inhibitor and might be utilized in the glioma antiangiogenesis therapy. PMID:22772605

Yuan, Bangqing; Xian, Ronghua; Ma, Jianfang; Chen, Yujian; Lin, Chuangan; Song, Yaoming

2012-07-07

366

Ferrous iron oxidation by Thiobacillus ferrooxidans: inhibition with benzoic acid, sorbic acid and sodium lauryl sulfate  

SciTech Connect

Acid mine drainage is formed by the weathering or oxidation of pyritic material exposed during coal mining. The rate of pyritic material oxidation can be greatly accelerated by certain acidophilic bacteria such as Thiobacillus ferrooxidans which catalyse the oxidation of ferrous to ferric iron. A number of organic compounds, under laboratory conditions, can apparently inhibit both the oxidation of ferrous to ferric iron by T. ferrooxidans and the weathering of pyritic material by mixed cultures of acid mine drainage micro-organisms. Sodium lauryl sulphate (SLS), an anionic surfactant has proved effective in this respect. Benzoic acid, sorbic acid and SLS at low concentrations, each effectively inhibited bacterial oxidation of ferrous iron in batch cultures of T. ferrooxidans. The rate of chemical oxidation of ferrous iron in low pH, sterile, batch reactors was not substantially affected at the tested concentrations of any of the compounds.

Onysko, S.J.

1984-07-01

367

POTENT INHIBITION OF HUMAN AP ENDONUCLEASE 1 BY ARYLSTIBONIC ACIDS  

PubMed Central

Human apurinic/apyrimidinic endonuclease (Ape1) plays an important role by processing the >10,000 highly toxic abasic sites generated in the genome of each cell every day. Ape1 has recently emerged as a target for inhibition as its overexpression in tumors has been linked with poor response to both radiation and chemotherapy and lower overall patient survival. Inhibition of Ape1 using siRNA or the expression of a dominant-negative form of the protein have been shown to sensitize cells to DNA-damaging agents, including various chemotherapeutic agents. However, potent small molecule inhibitors of Ape1 remain to be found. To this end, we screened Ape1 against the NCI Diversity Set of small molecules and discovered aromatic nitroso, carboxylate, sulfonamide and arylstibonic acid compounds with micromolar affinities for the protein. A further screen of a 37-compound arylstibonic acid sublibrary identified ligands with IC50 values in the range 4 to 300 nM. The negatively charged stibonic acids act by a partial-mixed mode, and likely serve as DNA phosphate mimics. These compounds provide a useful scaffold for development of chemotherapeutic agents against Ape1.

Seiple, Lauren A.; Cardellina, John H.; Akee, Rhone; Stivers, James T.

2009-01-01

368

Inhibition of breast tumor growth and angiogenesis by a medicinal herb: Ocimum sanctum  

PubMed Central

Ocimum sanctum (OS) is a traditionally used medicinal herb, which shows anti-oxidant, anti-carcinogenic, radio-protective and free radical scavenging properties. So far no detailed studies have been reported on its effects on human cancers. Thus, we analyzed its effects on human breast cancer utilizing in vitro and in vivo methodologies. Aqueous extracts were prepared from the mature leaves of Ocimum sanctum cultivated devoid of pesticides. Tumor progression and angiogenesis related processes like chemotaxis, proliferation, apoptosis, 3-dimensional growth and morphogenesis, angiogenesis, and tumor growth were studied in the presence or absence of the extract and in some experiments a comparison was made with purified commercially available eugenol, apigenin and ursolic acid. Aqueous OS leaf extract inhibits proliferation, migration, anchorage independent growth, three dimensional growth and morphogenesis, and induction of COX-2 protein in breast cancer cells. A comparative analysis with eugenol, apigenin and ursolic acid showed that the inhibitory effects on chemotaxis and three dimensional morphogenesis of breast cancer cells were specific to OS extract. In addition, OS extracts also reduced tumor size and neoangiogenesis in a MCF10 DCIS.com xenograft model of human DCIS. This is the first detailed report showing that OS leaf extract may be of value as a breast cancer preventive and therapeutic agent and might be considered as additional additive in the arsenal of components aiming at combating breast cancer progression and metastasis.

Nangia-Makker, Pratima; Tait, Larry; Hogan, Victor; Shekhar, Malathy P.V.; Funasaka, Tatsuyoshi; Raz, Avraham

2013-01-01

369

Growth-inhibiting effects of Paeonia lactiflora root steam distillate constituents and structurally related compounds on human intestinal bacteria.  

PubMed

The growth-inhibiting activities of Paeonia lactiflora (Paeoniaceae) root steam distillate constituents and structurally related compounds against nine harmful intestinal bacteria and eight lactic acid-producing bacteria were compared with those of two antibiotics, amoxicillin and tetracycline. Thymol, ?-terpinolene, (-)-perilla alcohol and (1R)-(-)-myrtenol exhibited high to extremely high levels of growth inhibition of all the harmful bacteria, whereas thymol and ?-terpinolene (except for Lactobacillus casei ATCC 393) inhibited the growth of all the beneficial bacteria (MIC, both 0.08-0.62 mg mL(-1)). Tetracycline and amoxicillin exhibited extremely high level of growth inhibition of all the test bacteria (MIC, <0.00002-0.001 mg mL(-1)). 1,8-Cineole, geraniol, (-)-borneol, (1S,2S,5S)-(-)-myrtanol, nerol, (S)-(-)-?-citronellol and (±)-lavandulol also exhibited inhibitory activity but with differing specificity and levels of activity. Structure-activity relationship indicates that structural characteristics, such as geometric isomerism, degrees of saturation, types of functional groups and types of carbon skeleton, appear to play a role in determining the growth-inhibiting activity of monoterpenoids. Global efforts to reduce the level of antibiotics justify further studies on naturally occurring P. lactiflora root-derived materials as potential preventive agents against various diseases caused by harmful intestinal bacteria such as clostridia. PMID:22805939

Ngan, Luong Thi My; Moon, Joon-Kwan; Kim, Jeong-Han; Shibamoto, Takayuki; Ahn, Young-Joon

2011-11-26

370

The inhibition of endothelial activation by unsaturated fatty acids.  

PubMed

Dietary long-chain fatty acids (FA) may influence pathological processes involving endothelial activation and leukocyte-endothelial interactions, such as inflammation and atherosclerosis. We previously showed that the n-3 FA docosahexaenoate (22:6n-3, DHA) inhibits cytokine-stimulated expression of endothelial-leukocyte adhesion molecules and soluble cytokines in the range of nutritionally achievable plasma concentrations. More recently we assessed structural determinants of VCAM-1 inhibition by FA. Cultured endothelial cells were incubated first with various saturated, monounsaturated, n-6 or n-3 polyunsaturated FA alone and then together with interleukin-1 or tumor necrosis factor. Saturated FA did not inhibit cytokine-induced endothelial activation, while a progressive increase in inhibitory activity was observed, for the same chain length, with the increase in double bonds accompanying the transition from monounsaturates to n-6 and, further, to n-3 FA. Comparison of various FA indicated no role of the double-bond position or configuration; the greater number of double bonds could explain the greater inhibitory activity of n-3 vs. n-6 FA. In order to ascertain mechanisms for these effects, we demonstrated inhibition of nuclear factor-kappaB (NF-kappaB) activation by DHA in parallel with a reduction in hydrogen peroxide (a critical mediator of NF-kappaB activation) released by endothelial cells either extracellularly or intracellularly. This suggests that a property related to fatty acid peroxidability (the presence of multiple double bonds) is related to inhibitory properties of hydrogen peroxide release and, consequently, of endothelial activation. PMID:10419145

De Caterina, R; Spiecker, M; Solaini, G; Basta, G; Bosetti, F; Libby, P; Liao, J

1999-01-01

371

Bifidobacterium longum-fermented broccoli supernatant inhibited the growth of Candida albicans and some pathogenic bacteria in vitro.  

PubMed

The aim of this study is to develop a growth inhibitory material against some pathogenic microorganisms, using beneficial bacteria such as Bifidobacterium species and certain types of vegetables which can be good substrates for the growth of the beneficial bacteria. At first, various vegetable juices were screened for the growth promotion of Bifidobacterium longum etc. Among the vegetables tested, broccoli (Brassica oleracea L. var. botrytis L.) and cabbage (Brassica oleracea L. var. capitata L.) showed excellent growth promoting activities for B. longum. Secondly, the B. longum-fermented broccoli (BFB) and Lactobacillus pentosus-fermented broccoli (LFB) supernatants were prepared and the growth inhibitory activities against Candida albicans were determined. Both of them showed dose-dependent, growth inhibitory effects, and the effect of BFB was superior to LFB. It was thought that the superior effect of BFB could be mainly attributed to the acids, especially acetic acid, produced by B. longum. BFB also inhibited some pathogenic bacteria such as Streptococcus mutans and Porphylomonas gingivalis. In conclusion, broccoli was found to be a good growth-promoting substance for B. longum. The fermented product, BFB, appears to be a usable material that inhibits the growth of C. albicans and some pathogenic bacteria. PMID:18661679

Suido, Hirohisa; Miyao, Manabu

2008-06-01

372

Maleic acid based scale inhibitors for calcium sulfate scale inhibition in high temperature application  

Microsoft Academic Search

In anhydrite rich reservoir rock, calcium sulfate is one of the dominant scale components which unlike carbonate scale are not easily removable by acid or dissolver treatment. To inhibit calcium sulfate scale formation in high temperature producing brine water systems, maleic acid–acrylic acid and maleic acid–acrylamide copolymers of appropriate molecular weight were synthesized and characterized and inhibition efficiency of the

B. Senthilmurugan; B. Ghosh; S. S. Kundu; M. Haroun; B. Kameshwari

2010-01-01

373

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

PubMed

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

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

2013-08-26

374

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

PubMed Central

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.

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

2013-01-01

375

Short Communication: Amino Acids Antagonistic to the Amino Acids Inhibitory for Growth Rate of Mixed Ruminal Bacteria  

Microsoft Academic Search

Antagonism of some amino acids (AA) to the inhibi- toryeffects ofotherAA(Ile, Phe,andThr)on thegrowth rate of mixed ruminal bacteria was investigated. In vitro growth rate of the mixed ruminal bacteria was inhibited when the 3 inhibitory AA (1 mM each) were each added to individual control treatments in which an ammonium salt was included as a sole N source. The inhibitory

H. Kajikawa; M. Mitsumori; K. Tajima; M. Kurihara

2005-01-01

376

Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes.  

PubMed

Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compound was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD50 of 30 microM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis. PMID:15558191

Napolitano, H B; Silva, M; Ellena, J; Rodrigues, B D G; Almeida, A L C; Vieira, P C; Oliva, G; Thiemann, O H

2004-11-17

377

Bradykinin-induced growth inhibition of normal rat kidney (NRK) cells is paralleled by a decrease in epidermal-growth-factor receptor expression.  

PubMed Central

Normal rat kidney fibroblasts, grown to density arrest in the presence of epidermal growth factor (EGF), can be induced to undergo phenotypic transformation by treatment with transforming growth factor beta or retinoic acid. Here we show that bradykinin blocks this growth-stimulus-induced loss of density-dependent growth arrest by a specific receptor-mediated mechanism. The effects of bradykinin are specific, and are not mimicked by other phosphoinositide-mobilizing agents such as prostaglandin F2 alpha. Northern-blot analysis and receptor-binding studies demonstrate that bradykinin also inhibits the retinoic acid-induced increase in EGF receptor levels in these cells. These studies provide additional evidence that EGF receptor levels modulate EGF-induced expression of the transformed phenotype in these cells. Images Figure 5

Van Zoelen, E J; Peters, P H; Afink, G B; Van Genesen, S; De Roos, D G; Van Rotterdam, W; Theuvenet, A P

1994-01-01

378

Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107  

Microsoft Academic Search

In addition to causing regression of the Mullerian duct in the male embryo, Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian cancer cells, which are known to be of Mullerian origin. Because the uterine cervix is derived from the same Mullerian duct precursor as the epithelium of the ovary, we tested the hypothesis that cervical cancer cells might

Thanh U. Barbie; David A. Barbie; David T. Maclaughlin; Shyamala Maheswaran; Patricia K. Donahoe

2003-01-01

379

Nucleic acid-based approaches to STAT inhibition  

PubMed Central

Silencing of abnormally activated genes can be accomplished in a highly specific manner using nucleic acid based approaches. The focus of this review includes the different nucleic acid based inhibition strategies such as antisense oligodeoxynucleotides, small interfering RNA (siRNA), dominant-negative constructs, G-quartet oligonucleotides and decoy oligonucleotides, their mechanism of action and the effectiveness of these approaches to targeting the STAT (signal transducer and activator of transcription) proteins in cancer. Among the STAT proteins, especially STAT3, followed by STAT5, are the most frequently activated oncogenic STATs, which have emerged as plausible therapeutic cancer targets. Both STAT3 and STAT5 have been shown to regulate numerous oncogenic signaling pathways including proliferation, survival, angiogenesis and migration/invasion.

Sen, Malabika; Grandis, Jennifer R.

2012-01-01

380

Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids  

Microsoft Academic Search

Retinoids have been shown to inhibit the growth of many human tumor cells including breast, ovarian and squamous cell carcinoma (SCC). While the exact mechanism of retinoid mediated growth suppression is not known, a role for the retinoic acid receptors (RARs) and retinoid X receptors (RXRs) has been established in both the breast and ovarian tumor cell models. We set

Quan Le; Marcia I Dawson; Dianne Robert Soprano; Kenneth J Soprano

2000-01-01

381

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

Microsoft Academic Search

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

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

2002-01-01

382

Promotion of plant growth by polymers of lactic acid  

Microsoft Academic Search

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

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

1990-01-01

383

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

PubMed Central

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.

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

384

Inhibition of 2,4-Dichlorophenoxyacetic Acid Conjugation to Amino Acids by Treatment of Cultured Soybean Cells with Cytokinins  

PubMed Central

Kinetin, and all other cytokinins tested, inhibited the conjugation of [14C]2,4-dichlorophenoxyacetic acid (2, 4-D) to amino acids when supplied simultaneously with the 2,4-D to cultured soybean cells. Upon transfer to hormone-free medium, the cytokinin-treated cells released more of their [14C]2,4-D than did the control cells. Initial exposure to low 2,4-D and high kinetin levels resulted in the greatest release of 2,4-D upon subsequent transfer. The observed alteration in 2,4-D metabolism did not seem to be correlated with growth rate. Appropriate treatment of soybean cells with kinetin resulted in 2,4-D metabolism that resembled the 2,4-D metabolism of embryogenic carrot cells. However, no new morphological structures were observed in these soybean cultures, indicating that other factors are related to the failure of soybean cells to regenerate in culture.

Montague, Michael J.; Enns, Russel K.; Siegel, Ned R.; Jaworski, Ernest G.

1981-01-01

385

Cytochrome p450 epoxygenase metabolism of arachidonic acid inhibits apoptosis.  

PubMed

The ubiquitous cytochrome P450 hemoproteins play important functional roles in the metabolism and detoxification of foreign chemicals. However, other than established roles in cholesterol catabolism and steroid hormone biosynthesis, their cellular and/or organ physiological functions remain to be fully characterized. Here we show that the cytochrome P450 epoxygenase arachidonic acid metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET) inhibits apoptosis induced by serum withdrawal, H(2)O(2), etoposide, or excess free arachidonic acid (AA), as determined by DNA laddering, Hoechst staining, and fluorescein isothiocyanate-labeled annexin V binding. In the stable transfectants (BM3 cells) expressing a mutant bacterial P450 AA epoxygenase, F87V BM3, which was genetically engineered to metabolize arachidonic acid only to 14,15-EET, AA did not induce apoptosis and protected against agonist-induced apoptosis. Ceramide assays demonstrated increased AA-induced ceramide production within 1 h and elevated ceramide levels for up to 48 h, the longest time tested, in empty-vector-transfected cells (Vector cells) but not in BM3 cells. Inhibition of cytochrome P450 activity by 17-octadecynoic acid restored AA-induced ceramide production in BM3 cells. Exogenous C2-ceramide markedly increased apoptosis in quiescent Vector cells as well as BM3 cells, and apoptosis was prevented by pretreatment of Vector cells with exogenous 14,15-EET and by pretreatment of BM3 cells with AA. The ceramide synthase inhibitor fumonisin B1 did not affect AA-induced ceramide production and apoptosis; in contrast, these effects of AA were blocked by the neutral sphingomyelinase inhibitor scyphostatin. The pan-caspase inhibitor Z-VAD-fmk had no effect on AA-induced ceramide generation but abolished AA-induced apoptosis. The antiapoptotic effects of 14,15-EET were blocked by two mechanistically and structurally distinct phosphatidylinositol-3 (PI-3) kinase inhibitors, wortmannin and LY294002, but not by the specific mitogen-activated protein kinase kinase inhibitor PD98059. Immunoprecipitation followed by an in vitro kinase assay revealed activation of Akt kinase within 10 min after 14,15-EET addition, which was completely abolished by either wortmannin or LY294002 pretreatment. In summary, the present studies demonstrated that 14,15-EET inhibits apoptosis by activation of a PI-3 kinase-Akt signaling pathway. Furthermore, cytochrome P450 epoxygenase promotes cell survival both by production of 14,15-EET and by metabolism of unesterified AA, thereby preventing activation of the neutral sphingomyelinase pathway and proapoptotic ceramide formation. PMID:11509673

Chen, J K; Capdevila, J; Harris, R C

2001-09-01

386

Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis.  

PubMed

Arachidonic acid (AA) and its metabolites have recently generated a heightened interest due to growing evidence of their significant role in cancer biology. Thus, inhibitors of the AA cascade, first and foremost COX inhibitors, which have originally been of interest in the treatment of inflammatory conditions and certain types of cardiovascular disease, are now attracting attention as an arsenal against cancer. An increasing number of investigations support their role in cancer chemoprevention, although the precise molecular mechanisms that link levels of AA, and its metabolites, with cancer progression have still to be elucidated. This article provides an overview of the AA cascade and focuses on the roles of its inhibitors and their implication in cancer treatment. In particular, emphasis is placed on the inhibition of cell proliferation and neo-angiogenesis through inhibition of the enzymes COX-2, 5-LOX and CYP450. Downstream effects of inhibition of AA metabolites are analysed and the molecular mechanisms of action of a selected number of inhibitors of catalytic pathways reviewed. Lastly, the benefits of dietary omega-3 fatty acids and their mechanisms of action leading to reduced cancer risk and impeded cancer cell growth are mentioned. Finally, a proposal is put forward, suggesting a novel and integrated approach in viewing the molecular mechanisms and complex interactions responsible for the involvement of AA metabolites in carcinogenesis and the protective effects of omega-3 fatty acids in inflammation and tumour prevention. PMID:19239926

Hyde, C A C; Missailidis, S

2009-02-23

387

15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival.  

PubMed

A 15-LOX, it is proposed, suppresses the growth of prostate cancer in part by converting arachidonic, eicosatrienoic, and/or eicosapentaenoic acids to n-6 hydroxy metabolites. These metabolites inhibit the proliferation of PC3, LNCaP, and DU145 prostate cancer cells but only at ?1-10 µM. We show here that the 15-LOX metabolites of docosahexaenoic acid (DHA), 17-hydroperoxy-, 17-hydroxy-, 10,17-dihydroxy-, and 7,17-dihydroxy-DHA inhibit the proliferation of these cells at ?0.001, 0.01, 1, and 1 µM, respectively. By comparison, the corresponding 15-hydroperoxy, 15-hydroxy, 8,15-dihydroxy, and 5,15-dihydroxy metabolites of arachidonic acid as well as DHA itself require ?10-100 µM to do this. Like DHA, the DHA metabolites a) induce PC3 cells to activate a peroxisome proliferator-activated receptor-? (PPAR?) reporter, express syndecan-1, and become apoptotic and b) are blocked from slowing cell proliferation by pharmacological inhibition or knockdown of PPAR? or syndecan-1. The DHA metabolites thus slow prostate cancer cell proliferation by engaging the PPAR?/syndecan-1 pathway of apoptosis and thereby may contribute to the prostate cancer-suppressing effects of not only 15-LOX but also dietary DHA. PMID:23029040

O'Flaherty, Joseph T; Hu, Yungping; Wooten, Rhonda E; Horita, David A; Samuel, Michael P; Thomas, Michael J; Sun, Haiguo; Edwards, Iris J

2012-09-20

388

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....

389

Aspirin Inhibits Colon Cancer Cell and Tumor Growth and Downregulates Specificity Protein (Sp) Transcription Factors  

PubMed Central

Acetylsalicylic acid (aspirin) is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NF?B). Moreover, we also showed by RNA interference that ?-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite.

Pathi, Satya; Jutooru, Indira; Chadalapaka, Gayathri; Nair, Vijayalekshmi; Lee, Syng-Ook; Safe, Stephen

2012-01-01

390

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 ...

391

Role of Caspases in 5-FU and Selenium Induced Growth Inhibition of Colorectal Cancer Cells  

PubMed Central

Background The mechanisms that could explain the poor sensitivity to 5-FU in certain colorectal cancer (CRC) cells were investigated and whether or not co-treatment with low doses of selenium would offer a therapeutic benefit, was explored. Materials and Methods Four CRC cell lines (Caco2, RKO, DLD1 and HT-29), with defined tumor signatures and seven different chemical forms of selenium were tested. Results 5-FU partially inhibited the HT-29 and RKO cells, but had a weak effect on the DLD1 and almost none on the Caco2 cells. Selenous acid and sodium selenite induced growth inhibition of the DLD1, RKO and HT-29 cells, with a marginal effect on the Caco2 cells. The Caco2 cells with mutant p53, failure to activate caspase-8, ?9, ?7 and ?3 and with hypermethylated caspase-8 were resistant to 5-FU. Conversely, RKO cells expressing wild type p53, proteolytically activated caspase-8, ?9, ?7 and ?3 and unmethylated caspase-8 were more responsive to 5-FU and selenous acid induced apoptosis. Conclusion Combination treatment with selenous acid may offer an efficacious strategy to overcome 5-FU resistance in certain CRC cells.

Thant, Aye Aye; Wu, Yanyuan; Lee, Jane; Mishra, Dhruva Kumar; Garcia, Heather; Koeffler, H. Phillip; Vadgama, Jaydutt V.

2013-01-01