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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

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

PubMed

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

Conková, E; Para, L; Kocisová, A

1993-01-01

4

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

5

Gymnemic acids inhibit hyphal growth and virulence in Candida albicans.  

PubMed

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

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

2013-01-01

6

Muricholic Acids Inhibit Clostridium difficile Spore Germination and Growth  

PubMed Central

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

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

2013-01-01

7

Inhibition of tumoral cell respiration and growth by nordihydroguaiaretic acid.  

PubMed

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

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

1994-11-16

8

Modeling the growth of Corynebacterium glutamicum under product inhibition in l-glutamic acid fermentation  

Microsoft Academic Search

In the fermentation of l-glutamic acid by Corynebacterium glutamicum, the growth inhibition by the substrate (glucose) at higher concentrations, and by the product at almost all concentrations seem to occur. In order to identify the range of concentrations for substrate limitation\\/inhibition, the experiments were conducted separately with different initial glucose concentrations. Proof of growth inhibition by the product was established

Noor Salam Khan; Indra Mani Mishra; R. P. Singh; Basheshwer Prasad

2005-01-01

9

Nordihydroguaiaretic Acid Inhibits Insulin-Like Growth Factor Signaling, Growth, and Survival in Human Neuroblastoma Cells  

PubMed Central

Neuroblastoma is a common pediatric malignancy that metastasizes to the liver, bone, and other organs. Children with metastatic disease have a less than 50% chance of survival with current treatments. Insulin-like growth factors (IGFs) stimulate neuroblastoma growth, survival, and motility, and are expressed by neuroblastoma cells and the tissues they invade. Thus, therapies that disrupt the effects of IGFs on neuroblastoma tumorigenesis may slow disease progression. We show that NVP-AEW541, a specific inhibitor of the IGF-I receptor (IGF-IR), potently inhibits neuroblastoma growth in vitro. Nordihydroguaiaretic acid (NDGA), a phenolic compound isolated from the creosote bush (Larrea divaricata), has anti-tumor properties against a number of malignancies, has been shown to inhibit the phosphorylation and activation of the IGF-IR in breast cancer cells, and is currently in Phase I trials for prostate cancer. In the present study in neuroblastoma, NDGA inhibits IGF-I-mediated activation of the IGF-IR and disrupts activation of ERK and Akt signaling pathways induced by IGF-I. NDGA inhibits growth of neuroblastoma cells and induces apoptosis at higher doses, causing IGF-I-resistant activation of caspase-3 and a large increase in the fraction of sub-G0 cells. In addition, NDGA inhibits the growth of xenografted human neuroblastoma tumors in nude mice. These results indicate that NDGA may be useful in the treatment of neuroblastoma and may function in part via disruption of IGF-IR signaling.

Meyer, Gary E.; Chesler, Louis; Liu, Dandan; Gable, Karissa; Maddux, Betty A.; Goldenberg, David D.; Youngren, Jack F.; Goldfine, Ira D.; Weiss, William A.; Matthay, Katherine K.; Rosenthal, Stephen M.

2010-01-01

10

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

NASA Astrophysics Data System (ADS)

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

Meguro, Ayano; Sato, Yutaka

2014-04-01

11

An Explanation of the Inhibition of Root Growth Caused by Indole-3-Acetic Acid 1  

PubMed Central

Low concentrations of indole-3-acetic acid inhibit the growth of pea root sections by inducing the formation of the growth regulator, ethylene gas. Ethylene is produced within 15 to 30 minutes after indole-3-acetic acid is applied and roots begin to swell immediately after they are exposed to the gas. Carbon dioxide competitively inhibits ethylene action in roots, impedes their geotropic response, and partially reinstates auxin inhibited growth. It is concluded that ethylene participates in the geotropic response of roots, but not that of stems. Images

Chadwick, Arthur V.; Burg, Stanley P.

1967-01-01

12

All-fra\\/is-retinoic Acid Inhibits the Growth of Human RhabdomyosarcomaCell Lines  

Microsoft Academic Search

We have been evaluating the role of all-fra\\/w-retinoic acid (RA) in the differentiation and growth of human rhabdomyosarcoma (RMS) cell lines. Treatment of both embryonal (RD) and alveolar (RH30) human RMS cell lines with all-f ranv-KA resulted in a dose-dependent inhibition of cell growth with a maximal inhibition of 92 and 66%, respectively, at 5 x 10~* M. When 13-cw-RA

Gary D. Crouch; Lee J. Helman

1991-01-01

13

Auxin-Induced Ethylene Triggers Abscisic Acid Biosynthesis and Growth Inhibition1  

PubMed Central

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

Hansen, Hauke; Grossmann, Klaus

2000-01-01

14

Microbial-growth inhibition during composting of food waste: effects of organic acids.  

PubMed

Factorial designs were employed to analyze the inhibitory effects of acetic, butyric, lactic, and propionic acids on composting microorganisms. Compost samples were withdrawn on different days of composting and treated with acids alone and in combination (at 0 and 0.5 mmol/g). Microorganisms were enumerated to determine degree of growth inhibition. Generally, inhibition was more severe on the day when pH decreased rather than on the day when pH started to increase. Butyric or lactic acid alone, and the combination of butyric, lactic, and propionic acids, significantly inhibited thermophilic bacteria. Only 51.0-65.0% of the thermophilic bacteria exist if 0.5 mmol/g of these acids were present in compost. Temperature, microbial populations, and microbial growth phase might cause variation in the inhibitory effects of acids. These findings are useful not only in the study of microorganisms in acidic microenvironments, but also in preventing microbial-growth inhibition by predicting population via a regression model. PMID:20363618

Cheung, H N B; Huang, G H; Yu, H

2010-08-01

15

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

Microsoft Academic Search

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

2000-01-01

16

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

17

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

PubMed

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

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

2012-12-01

18

Inhibition of the growth of Salmonella typhimurium ST10 by propionic acid and chloride salts  

Microsoft Academic Search

The ability of propionic acid and chloride salts to inhibit Salmonella typhimurium growth was determined. Brain–heart infusion (BHI) was supplemented with 0, 250, 500, or 750 m M of potassium chloride (KCl), sodium chloride (NaCl), or 0, 125, 250, or 375 m M of both KCl and NaCl. Propionic acid was added to the BHI and BHI salts to produce

A. Hinton Jr

1999-01-01

19

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

20

Mechanism of inhibition of tannic acid and related compounds on the growth of intestinal bacteria.  

PubMed

Tannic acid, propyl gallate and methyl gallate, but not gallic acid, were found to be inhibitory to the growth of intestinal bacteria Bacteroides fragilis ATCC 25285, Clostridium clostridiiforme ATCC 25537, C. perfringens ATCC 13124, C. paraputrificum ATCC 25780, Escherichia coli ATCC 25922, Enterobacter cloacae ATCC 13047, Salmonella typhimurium TA98 and S. typhimurium YG1041 at 100-1000 microg/ml in culture broth. Neither Bifidobacterium infantis ATCC 15697 nor Lactobacillus acidophilus ATCC 4356 was inhibited by any of the above compounds up to 500 microg/ml. Tannic acid has a much greater relative binding efficiency to iron than propyl gallate, methyl gallate or gallic acid. The inhibitory effect of tannic acid to the growth of intestinal bacteria may be due to the strong iron binding capacity of tannic acid; whereas the effect of propyl gallate and methyl gallate probably occurs by a different mechanism. The growth of E. coli was restored by the addition of iron to the medium after the precipitate caused by tannic acid was removed. Neither B. infantis nor L. acidophilus require iron for growth. This probably contributes to their resistance to tannic acid. Because tannins are abundant in the human diet, tannins may affect the growth of some intestinal bacteria and thus may have an impact on human health. PMID:9862646

Chung, K T; Lu, Z; Chou, M W

1998-12-01

21

Growth inhibition of Cronobacter spp. strains in reconstituted powdered infant formula acidified with organic acids supported by natural stomach acidity.  

PubMed

Cronobacter is associated with outbreaks of rare, but life-threatening cases of meningitis, necrotizing enterocolitis, and sepsis in newborns. This study was conducted to determine the effect of organic acids on growth of Cronobacter in laboratory medium and reconstituted powdered infant formula (PIF) as well as the bacteriostatic effect of slightly acidified infant formula when combined with neonatal gastric acidity. Inhibitory effect of seven organic acids on four acid sensitive Cronobacter strains was determined in laboratory medium with broth dilution method at pH 5.0, 5.5 and 6.0. Acetic, butyric and propionic acids were most inhibitive against Cronobacter in the laboratory medium. The killing effect of these three acids was partially buffered in reconstituted PIF. Under neonatal gastric acid condition of pH 5.0, the slightly acidified formula which did not exert inhibition effect solely reduced significantly the Cronobacter populations. A synergistic effect of formula moderately acidified with organic acid combined with the physiological infant gastric acid was visible in preventing the rapid growth of Cronobacter in neonatal stomach. The study contributed to a better understanding of the inhibitory effect of organic acids on Cronobacter growth in different matrixes and provided new ideas in terms of controlling bacteria colonization and translocation by acidified formula. PMID:23664263

Zhu, S; Schnell, S; Fischer, M

2013-09-01

22

Peptide nucleic acids inhibit growth of Brucella suis in pure culture and in infected murine macrophages  

PubMed Central

Peptide nucleic acids (PNAs) are single-stranded, synthetic nucleic acid analogues containing a pseudopeptide backbone in place of the phosphodiester sugar–phosphate. When PNAs are covalently linked to cell-penetrating peptides (CPPs) they readily penetrate the bacterial cell envelope, inhibit expression of targeted genes and cause growth inhibition both of Gram-positive and Gram-negative bacteria. However, the effectiveness of PNAs against Brucella, a facultative intracellular bacterial pathogen, was unknown. The susceptibility of a virulent Brucella suis strain to a variety of PNAs was assessed in pure culture as well as in murine macrophages. The studies showed that some of the PNAs targeted to Brucella genes involved in DNA (polA, dnaG, gyrA), RNA (rpoB), cell envelope (asd), fatty acid (kdtA, acpP) and protein (tsf) synthesis inhibit the growth of B. suis in culture and in macrophages after 24 h of treatment. PNA treatment inhibited Brucella growth by interfering with gene expression in a sequence-specific and dose-dependent manner at micromolar concentrations. The most effective PNA in broth culture was that targeting polA at ca. 12 ?M. In contrast, in B. suis-infected macrophages, the most effective PNAs were those targeting asd and dnaG at 30 ?M; both of these PNAs had little inhibitory effect on Brucella in broth culture. The polA PNA that inhibits wild-type B. suis also inhibits the growth of wild-type Brucella melitensis 16M and Brucella abortus 2308 in culture. This study reveals the potential usefulness of antisense PNA constructs as novel therapeutic agents against intracellular Brucella.

Rajasekaran, Parthiban; Alexander, Jeffry C.; Seleem, Mohamed N.; Jain, Neeta; Sriranganathan, Nammalwar; Wattam, Alice R.; Setubal, Joao C.; Boyle, Stephen M.

2012-01-01

23

Synergy of ferrous ion on 5-aminolevulinic acid-mediated growth inhibition of Plasmodium falciparum.  

PubMed

Haem biosynthesis appeared to be a target of malaria therapy because 5-aminolevulinic acid (ALA), a haem biosynthesis starting material, with light exposure or a high amount of ALA alone reduced Plasmodium falciparum growth to undetectable level. However, the administration of a high dose of ALA is unrealistic for clinical therapy. We found that Fe(2+) enhanced P. falciparum-killing potency of ALA and significantly inhibited the parasite growth. The intermediates of haem biosynthesis localized to the parasite organelles, and coproporphyrin III was the most accumulated intermediate. These novel findings may lead to development of a new anti-malarial drug using ALA and Fe(2+). PMID:24158489

Komatsuya, Keisuke; Hata, Masayuki; Balogun, Emmanuel O; Hikosaka, Kenji; Suzuki, Shigeo; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo; Ogura, Shun-Ichiro; Sato, Shigeharu; Kita, Kiyoshi

2013-12-01

24

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

PubMed Central

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

2013-01-01

25

Mechanism of Growth Inhibition of Prostate Cancer Xenografts by Valproic Acid  

PubMed Central

Valproic Acid (VPA), a histone deacetylase inhibitor, has been demonstrated to cause a marked decrease in proliferation of prostate cancer (PCa) cells in vitro and a significant reduction in tumor volume in vivo. The goal of this study is to better understand the VPA-induced growth inhibition in vivo, by studying expression of various markers in PCa xenografts. Methods. For in vitro experiments, PCa cells were treated with 0, 0.6, and 1.2?mM VPA for 14 days. For in vivo models, experimental animals received 0.4% VPA in drinking water for 35 days. Tissue microarray was generated using cell pellets and excised xenografts. Results. VPA treatment causes cell cycle arrest in PCa cells in vivo, as determined by increase in p21 and p27 and decrease in cyclin D1 expression. Increased expression of cytokeratin18 was also seen in xenografts. LNCaP xenografts in treated animals had reduced androgen receptor (AR) expression. While decreased proliferation was found in vitro, increase in apoptosis was found to be the reason for decreased tumor growth in vivo. Also, an anti-angiogenic effect was observed after VPA treatment. Conclusion. VPA inhibits tumor growth by multiple mechanisms including cell cycle arrest, induction of differentiation, and inhibition of growth of tumor vasculature.

Sidana, Abhinav; Wang, Muwen; Shabbeer, Shabana; Chowdhury, Wasim H.; Netto, George; Lupold, Shawn E.; Carducci, Michael; Rodriguez, Ronald

2012-01-01

26

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

PubMed Central

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

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

2009-01-01

27

Inhibition of cell growth and telomerase activity of breast cancer cells in vitro by retinoic acids.  

PubMed

The effects of retinoic acid (RA) and its analogs, all-trans RA, 9-cis RA and 13-cis RA, were investigated in human breast cancer MCF-7 cells and immortalized breast epithelial cell line MCF-10A. RA inhibited the telomerase activity of MCF-7 cells in a wide range of concentrations. RA at 10 microM also inhibited the growth of MCF-7 cells in a time-dependent manner. However, no significant growth inhibition was found between untreated control and RA-treated MCF-10A cells. Moreover, a marked inhibition of telomerase activity by RA was detected early in MCF-7 cells (after 24 h of RA treatment), which was preceded by a reduction of hTERT mRNA expression (after 12 h of RA treatment). However, MCF-10A cells showed a reduction of telomerase activity and down-regulation of hTERT after 4 days of RA treatment. Simultaneous changes in hTERT mRNA expression and telomerase activity were found for MCF-10A cells. The expressions of hTR and hTEP1 telomerase component genes were not changed after RA treatment. These results indicate that the anti-breast cancer activity of RA could be mediated by its ability to down-regulate the expression of hTERT telomerase gene. PMID:11029500

Choi, S H; Kang, H K; Im, E O; Kim, Y J; Bae, Y T; Choi, Y H; Lee, K H; Chung, H Y; Chang, H K; Kim, N D

2000-11-01

28

Inhibition of the growth of 12V-ras-transformed rat fibroblasts by acetylsalicylic acid correlates with inhibition of NF-kappa B.  

PubMed

Epidemiological studies have demonstrated a correlation between regular aspirin (acetylsalicylic acid; ASA) use and a decreased risk for the development of cancer. We here show that ASA inhibits the growth of 12V-ras-transformed rat fibroblasts in vitro at pharmacological concentrations. This effect appeared to be unrelated to inhibition of cyclooxygenase, since other cyclooxygenase inhibitors did not inhibit cell growth. A number of nuclear transcription factors have been implicated as mediators of transformation. ASA has recently been reported to inhibit the activation of one such factor, NF-kappa B. We found that NF-kappa B binding activity was decreased in ASA-treated 12V-ras-transformed cells. Inhibition of NF-kappa B activation was not due to a general inhibitory effect, since AP-1 binding activity was not affected. We conclude that ASA inhibits the growth of 12V-ras-transformed fibroblasts, possibly via inhibition of NF-kappa B. PMID:9147613

Ljungdahl, S; Shoshan, M C; Linder, S

1997-01-01

29

Effects of salvianolic acid B on in vitro growth inhibition and apoptosis induction of retinoblastoma cells  

PubMed Central

AIM To observe the effects of salvianolic acid B (SalB) on in vitro growth inhibition and apoptosis induction of retinoblastoma HXO-RB44 cells. METHODS The effects of SalB on the HXO-RB44 cells proliferation in vitro were observed by MTT colorimetric method. The morphological changes of apoptosis before and after the treatment of SalB were observed by Hoechst 33258 fluorescent staining method. Apoptosis rate and cell cycle changes of HXO-RB44 cells were detected by flow cytometer at 48 hours after treated by SalB. The expression changes of Caspase-3 protein in HXO-RB44 cells were detected by Western Blot. RESULTS SalB significantly inhibited the growth of HXO-RB44 cells, while the inhibition was in a concentration-and time-dependent manner. The results of fluorescent staining method indicated that HXO-RB44 cells showed significant phenomenon of apoptosis including karyorrhexis, fragmentation and the formation of apoptotic bodies, etc. after 24, 48 and 72 hours co-culturing of SalB and HXO-RB44 cells. The results of flow cytometer showed that the apoptosis rate and the proportion of cells in S phase were gradually increased at 48 hours and 72 hours after treated by different concentrations of SalB. Western Blot strip showed that the expression of Caspase-3 protein in HXO-RB44 cells was gradually increased with the increase of the concentration of SalB. CONCLUSION SalB can significantly affect on HXO-RB44 cells growth inhibition and apoptosis induction which may be achieved through the up-regulation of Caspase-3 expression and the induction of cell cycle arrest.

Liu, Xing-An

2012-01-01

30

Metalloporphyrin synergizes with ascorbic acid to inhibit cancer cell growth through fenton chemistry.  

PubMed

Ascorbic acid (AA) has been reported to inhibit tumor cell growth through the generation of extracellular hydrogen peroxide (H(2)O(2)). However, the clinical utility of AA has been limited by relatively low potency and in vivo efficacy. This study reports that the metalloporphyrin, Mn(III) tetrakis(N-methylpyridinium-2-yl)porphyrin(5+) (MnTMPyP), has a potent synergistic cytotoxic effect when combined with AA in a variety of cancer cell lines. In the presence of MnTMPyP, the concentration of AA required to inhibit cancer cell growth was markedly reduced. In vitro (cell-free) experiments demonstrated that AA alone enhanced the Fenton reaction that produces cytotoxic hydroxyl radical (HO(*)); however, this reaction was limited by the low rate by which AA generates H(2)O(2) (Fenton reaction substrate) from O(2). MnTMPyP catalyzed H(2)O(2) generation through the AA-facilitated Mn(II <--> III)TMPyP redox cycle and thereby markedly potentiated the Fenton reaction. Accordingly, MnTMPyP and AA resulted in increased cellular levels of H(2)O(2) and HO(*) in cancer cells, which mediate the synergistic cytotoxicity of this combined treatment. This effect was inhibited by cellular enzymes that metabolize H(2)O(2), such as catalase and glutathione peroxidase, suggesting that selective killing of cancer cells deficient in such enzymes can be achieved in vivo. PMID:20735206

Tian, Junqiang; Peehl, Donna M; Knox, Susan J

2010-08-01

31

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

PubMed Central

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.

Murzyn, Anna; Krasowska, Anna; Stefanowicz, Piotr; Dziadkowiec, Dorota; Lukaszewicz, Marcin

2010-01-01

32

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

USGS Publications Warehouse

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

Reddy, Michael M.; Leenheer, Jerry

2011-01-01

33

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

PubMed Central

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

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

2013-01-01

34

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

35

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

USGS Publications Warehouse

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

Michael M Reddy

2012-01-01

36

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

NASA Astrophysics Data System (ADS)

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

Reddy, Michael M.

2012-08-01

37

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

PubMed Central

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

Parkinson, Eric Kenneth

2013-01-01

38

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

Microsoft Academic Search

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

Peter Kurdi; Koji Kawanishi; Kanako Mizutani; Atsushi Yokota

2006-01-01

39

GrowthInhibition ofStreptococcus mutansbyCellular Extracts of HumanIntestinal Lactic AcidBacteria  

Microsoft Academic Search

Theinvitro growth ofStreptococcus mutanswas completely inhibited bywater-soluble extracts fromcells of various intestinal lactic acidbacteria identified asStreptococcus faecium, Streptococcus equinus, Lactobacillus fermentum, andLactobacillus salivarius. Thegrowthinhibition was dependent on theconcentrations ofthe extracts. Incontrast, theextracts didnotinhibit thegrowthofthemajorindigenous intestinal lactic acid bacteria isolated fromhumans.Theselactic acidbacteria were notacutely toxic inmice. Inhibition ofthegrowth ofStreptococcus mutans, which hasbeenconsidered amajorpathogen ofdental caries, is thought tobeoneofthemostimportant factors inpreventing dental

KAZUOKI ISHIHARA; HIROKO MIYAKAWA; ATSUKO HASEGAWA; YASUO KAWAI

1985-01-01

40

Milk fat conjugated linoleic acid (CLA) inhibits growth of human mammary MCF-7 cancer cells.  

PubMed

The relationship between growth and the antioxidant enzyme defence system in human MCF-7 (breast) cancer cells treated with bovine milk fat enriched with conjugated linoleic acid (CLA) was studied. Milk enriched in CLA was obtained from cows on pasture supplemented with full fat rapeseeds and full fat soyabeans (1). Cell number decreased up to 90% (p < 0.05) and lipid peroxidation increased 15-fold (p < 0.05) following incubation of MCF-7 cells for 8 days with increasing levels of milk fat yielding CLA concentrations between 16.9 and 22.6 ppm. Growth suppression and prooxidant effects of milk fat CLA were independent of the variable composition of the milk fat samples, suggesting that CLA was the active ingredient in milk fat responsible for the cytotoxic effect. Mixtures containing isomers of CLA (c9, t11-, t10, c12-, c11, t13- and minor amounts of other isomers) and linoleic acid (LA) at similar concentrations to the milk fat samples were as effective at inhibiting growth and stimulating peroxidation of MCF-7 cells as the milk fatty acids. Incubation of the cells with the c9, t11 CLA isomer (20 ppm) or the mixture of CLA isomers (20 ppm) for 8 days resulted in a 60% decrease (p < 0.05) in viability compared with untreated controls and was significantly (p < 0.05) more effective than incubation with the t10, c12 CLA isomer (20 ppm), which caused only a 15% decrease in cell numbers under similar conditions. A 25% increase (p < 0.05) in cell proliferation occurred when LA (20 ppm) alone was incubated with MCF-7 cells for 8 days. 14C-CLA was preferentially incorporated into the phospholipid fraction of the MCF-7 cell lipids in a dose-dependent manner and CLA accumulated in cell membranes more efficiently when the cells were incubated in the presence of milk fat than the c9, t11 synthetic CLA isomer. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities were induced in MCF-7 cells exposed to milk fat (containing 16.9-22.6 ppm CLA) over 8 days. The data indicate that milk fat triglyceride-bound CLA, consisting primarily of the c9, t11 isomer, was cytotoxic towards MCF-7 cells. PMID:11131667

O'Shea, M; Devery, R; Lawless, F; Murphy, J; Stanton, C

41

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

2011-09-15

42

Lactic acid bacteria in an alginate film inhibit Listeria monocytogenes growth on smoked salmon  

Microsoft Academic Search

Antimicrobial packaging with lactic acid bacteria incorporated into the film matrix is a novel approach for controlling the growth of food-borne pathogens in ready-to-eat food. The overall objective of this study was to assess the effect of two strains of lactic acid bacteria (LAB) and nisin trapped in an alginate matrix, on Listeria monocytogenes growth on vacuum packed cold-smoked salmon.

Aníbal Concha-Meyer; Renate Schöbitz; Carmen Brito; Ricardo Fuentes

2011-01-01

43

Competitive Inhibition of Amino Acid Uptake Suppresses Chlamydial Growth: Involvement of the Chlamydial Amino Acid Transporter BrnQ  

Microsoft Academic Search

Chlamydiaceae are obligate intracellular bacterial pathogens that strictly depend on host metabolites, such as nucleotides, lipids, and amino acids. Depletion of amino acids in cell culture media results in abnormal chlamydial development in vitro. Surprisingly, enrichment of certain amino acids also retards chlamydial growth. Our experiments revealed that the antichlamydial effects are largely independent of changes in the host cell

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

2008-01-01

44

Inhibition of hair growth  

US Patent & Trademark Office Database

A method of inhibiting hair growth in a mammal includes applying, to an area of skin from which reduced hair growth is desired, a dermatologically acceptable composition containing a non-steroidal suppressor of angiogenesis.

2000-07-25

45

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

46

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

PubMed

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

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

2014-07-01

47

Tolfenamic acid inhibits colon cancer cell and tumor growth and induces degradation of specificity protein (Sp) transcription factors.  

PubMed

Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug (NSAID) that inhibits lung, esophageal, breast and pancreatic cancer cell and tumor growth, and this study investigated the anticancer activity of TA in colon cancer. TA inhibited growth and induced apoptosis in RKO, SW480, HT-29, and HCT-116 colon cancer cells, and TA (50 mg/kg/d) also inhibited tumor growth in athymic nude mice bearing RKO cells as xenografts. TA downregulated expression of Sp proteins (Sp1, Sp3, and Sp4) in colon cancer cells and this was accompanied by decreased expression of several Sp-regulated growth promoting (cyclin D1, hepatocyte growth factor receptor), angiogenic (vascular endothelial growth factor (VEGF) and its receptor 1), survival (survivin and bcl-2), and inflammatory (NF?Bp65/p50) gene products. The mechanism of TA-mediated effects on Sp proteins was due to activation of caspases. These results now extend the number of NSAIDs that may have clinical potential for colon cancer chemotherapy and show that the anticancer activity of TA is due, in part, to targeting Sp transcription factors. PMID:23670891

Pathi, Satya; Li, Xi; Safe, Stephen

2014-02-01

48

Metabolic effects of free fatty acids during endotoxaemia in a porcine model--free fatty acid inhibition of growth hormone secretion as a potential catabolic feedback mechanism.  

PubMed

Critical illness and severe inflammation are catabolic states characterised by breakdown of tissue and protein stores, by increased levels of free fatty acids, and by insulin resistance. These metabolic features contribute to morbidity and mortality. Growth hormone and insulin are the two major anabolic hormones. The present study was designed to test whether increased levels of free fatty acids (i) inhibit growth hormone secretion and (ii) induce insulin resistance during acute endotoxin exposure in a porcine model of critical illness. We studied 20 pigs for 6 h during combined anaesthesia and endotoxin infusion and a hyperinsulinaemic glucose clamp to control glucose, insulin, and free fatty acid concentrations. Pigs were randomised to two different continuous infusion rates of Intralipid resulting in different, sustained, and elevated free fatty acid concentrations (1.63 mmol l(-1) vs. 0.58 mmol l(-1), p=0.0002). Concomitantly, we observed reduced growth hormone concentrations in the group with high free fatty acid concentrations (3.5 ng ml(-1) vs. 6.6 ng ml(-1), p<0.003). No difference in insulin sensitivity, measured as the glucose infusion rate necessary to maintain euglycaemia, was observed. We conclude that high levels of free fatty acids reduce circulating growth hormone concentrations in porcine endotoxaemia; this probably constitutes a negative feedback mechanism whereby growth hormone induced-stimulation of free fatty acids release inhibit growth hormone secretion. This mechanism may further contribute to protein loss in critical illness. We found no evidence that the increment of plasma free fatty acids between groups contribute to insulin resistance in critical illness. PMID:20195947

Buhl, M; Gjedsted, J; Granfeldt, A; Larsen, P Ø; Schmitz, O; Tønnesen, E; Møller, N

2010-05-01

49

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

50

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

51

Amino acid alcohols: growth inhibition and induction of differentiated features in melanoma cells.  

PubMed

The effects of a series of D- and L-amino acid alcohols on the proliferation and phenotypic expression of B16 mouse melanoma cells were evaluated. B16 melanoma cells were incubated for different time intervals in the presence of D- or L-phenylalaninol (PHE), D- or L-alaninol (AL), D- or L-leucinol (LE), L-histidinol (HIS), L-tyrosinol (TYR) and L-methioninol (MET). All agents, including the D or L configuration, induced an anti-proliferative effect, although of considerably different magnitude. D-PHE was the most active growth inhibitor. The growth inhibitory effects were accompanied by phenotypic alterations, which included morphological changes and enhancement in the activities of NADPH cytochrome c reductase and tau-glutamyl transpeptidase. These phenotypic alterations correlated with the growth inhibitory effects of the different agents and seem to reflect a higher differentiated state. PMID:8099846

Landau, O; Wasserman, L; Deutsch, A A; Reiss, R; Panet, H; Novogrodsky, A; Nordenberg, J

1993-05-14

52

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

2013-12-01

53

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

54

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

SciTech Connect

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

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

2011-08-24

55

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

56

Determination of citric acid based on inhibition of the crystal growth of calcium fluoride.  

PubMed

Inhibition of the growth of calcium fluoride crystals in the presence of citrate was followed using a kinetic-potentiometric technique and a calcium ion-selective electrode, and as a consequence, a method for the determination of citrate in the range 0.5-2.4 micrograms ml-1 has been developed. The method was successfully applied to the determination of citrate contained in pharmaceutical products and urine. Urine analysis requires prior separation of phosphate, sulphate and magnesium(II). Elimination of these interferences was studied and accomplished using precipitation processes. Magnesium and phosphate were jointly eliminated in basic media by the addition of ammonium ions. Phosphate and sulphate were eliminated with barium(II). Phosphate was also eliminated as a lithium salt. PMID:2008941

Grases, F; Costa-Bauzá, A; March, J G

1991-01-01

57

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

PubMed Central

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

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

2012-01-01

58

Betulinic Acid inhibits growth of cultured vascular smooth muscle cells in vitro by inducing g(1) arrest and apoptosis.  

PubMed

Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC) is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC(50) of 3.8??g/mL significantly (P < 0.05). Nevertheless, betulinic acid exhibited G(1) cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24?h of treatment. In conclusion, betulinic acid induced G(1) cell cycle arrest and dose-dependent DNA damage on VSMC. PMID:23056140

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

2012-01-01

59

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

PubMed

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

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

2009-07-15

60

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

61

Caffeic Acid Phenethyl Ester (CAPE) derived from propolis, a honeybee product, inhibits growth of breast cancer stem cells.  

PubMed

Cancer stem cells (CSC) are chemoresistant and implicated in tumor recurrence, metastasis and high patient mortality; thus substances impairing CSC activity, could be invaluable as novel cancer therapeutics. We previously showed that CAPE (caffeic acid phenethyl ester), a component of propolis, a honeybee product, inhibits growth of MDA-MB-231 (MDA-231) cells, mdr gene expression, NF-?B, EGFR, and VEGF. We hypothesized that CAPE also acts by interfering with CSC-mediated effects. We isolated breast CSC (bCSC) from MDA-231 cells, a model of human triple-negative breast cancer, and mouse xenografts. bCSC grow as mammospheres (MMS) and when dissociated into single cells, form MMS again, a sign of self-renewal. bCSC exhibited the characteristic CD44(+)/CD24(-/low) phenotype and generated progenitors in the presence of serum, a CSC trait responsible for regenerating tumor mass. CAPE caused dose-dependent bCSC self-renewal inhibition and progenitor formation. Clonal growth on soft agar was inhibited dose-dependently, but apoptosis was not induced as determined by Annexin-V/PI assay. Instead, bCSC were noted to significantly progress from a quiescent cell cycle state in G0/G1 (82%), S phase (12%) to a cycling state with an increase in S phase (41%) and subsequent decrease in G0/G1 (54%). Treatment of bCSC with CAPE (4.5-days) decreased CD44 levels by 95%, while another cell population containing 10-100-fold lower CD44 content concurrently increased. Results suggest that CAPE causes pronounced changes in bCSC characteristics manifested by inhibition of self renewal, progenitor formation, clonal growth in soft agar, and concurrent significant decrease in CD44 content, all signs of decreased malignancy potential. PMID:21537887

Omene, Coral O; Wu, Jing; Frenkel, Krystyna

2012-08-01

62

[Mechanism of inhibiting the cell growth in diffuse large B-cell lymphoma by valproic acid combined with temsirolimus].  

PubMed

The aim of this study was to illustrate the mechanism of inhibiting the cell growth in diffuse large B-cell lymphoma by histone deacetylase inhibitor valproic acid (VPA) combined with mTOR inhibitor temsirolimus (TEM). MTT assay and Wright's stain were used to assess cell growth inhibition and to detect the cell morphological changes respectively. The cell apoptosis, cell cycle and cell autophagy were determined by flow cytometry. Ultrastructure changes were confirmed by electron microscopy. Protein changes were detected by Western blot. The results showed that both VPA and TEM alone inhibited cell proliferation and the effect was more obvious in the combination group. VPA combined with TEM induced cell arrest in G0/G1 phase and upregulated the expression of autophagy-related protein LC3, without cell apoptosis. Moreover, typical autophagosomes were observed, further confirming the presence of autophagy. Western blot showed the changes of proteins involved in autophagy signaling pathway. VPA decreased HDAC1 and HDAC3 expression and increased histone acetylation, suggesting that VPA also affected lymphoma cell proliferation through epigenetic modification. It is concluded that the combined treatment of VPA and TEM induces cell cycle arrest and cell autophagy, which provides a new clue for their clinical application in diffuse large B-cell lymphoma. PMID:24370026

Zheng, Zhong; Zhao, Yan; Dong, Li-Hua; Wang, Li; Cheng, Shu; Zhao, Wei-Li

2013-12-01

63

Accumulation, assimilation and growth inhibition of copper on freshwater alga ( Scenedesmus subspicatus 86.81 SAG) in the presence of EDTA and fulvic acid  

Microsoft Academic Search

Accumulation and growth inhibition of Cu to fresh water alga (Scenedesmus subspicatus 86.81 SAG) and the influences of ethylenediaminetetraacetic acid (EDTA) and fulvic acid (FA) were examined. These results demonstrated that both EDTA and FA could reduce toxicity of Cu to alga by the way of preventing Cu from being adsorbed by cell wall of alga. When dissolved Cu (Cudissolved),

Mei Ma; Wangzhao Zhu; Zijian Wang; Geert J. Witkamp

2003-01-01

64

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

PubMed

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

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

2010-03-01

65

Ursolic acid inhibits multiple cell survival pathways leading to suppression of growth of prostate cancer xenograft in nude mice.  

PubMed

Activation of transcription factors nuclear factor-?B (NF-?B) and signal transducer and activator of transcription 3 (STAT3) is frequently observed in prostate cancer and has been linked with tumor cell proliferation, invasion, metastasis, and angiogenesis. In this study, we investigated the effect of ursolic acid (UA) on NF-?B and STAT3 signaling pathways in both androgen-independent (DU145) and androgen-dependent (LNCaP) prostate cancer cell lines and also prospectively tested the hypothesis of NF-?B and STAT3 inhibition using a virtual predictive functional proteomics tumor pathway technology platform. We found that UA inhibited constitutive and TNF-?-induced activation of NF-?B in DU145 and LNCaP cells in a dose-dependent manner. The suppression was mediated through the inhibition of constitutive and TNF-?-induced I?B kinase (IKK) activation, phosphorylation of I?B? and p65 and NF-?B-dependent reporter activity. Furthermore, UA suppressed both constitutive and inducible STAT3 activation in prostate cancer cells concomitant with suppression of activation of upstream kinases (Src and JAK2) and STAT3-dependent reporter gene activity. UA also downregulated the expression of various NF-?B and STAT3 regulated gene products involved in proliferation, survival, and angiogenesis and induced apoptosis in both cells lines as evidenced by DNA fragmentation and annexin V staining. In vivo, UA (200 mg/kg b.w.) treated for 6 weeks inhibited the growth of DU145 cells in nude mice without any significant effect on body weight. Overall, our results from experimental and predictive studies suggest that UA mediates its anti-tumor effects through suppression of NF-?B and STAT3 pathways in prostate cancer. PMID:21465181

Shanmugam, Muthu K; Rajendran, Peramaiyan; Li, Feng; Nema, Tarang; Vali, Shireen; Abbasi, Taher; Kapoor, Shweta; Sharma, Ashish; Kumar, Alan Prem; Ho, Paul C; Hui, Kam M; Sethi, Gautam

2011-07-01

66

Gambogic acid inhibits the growth of osteosarcoma cells in vitro by inducing apoptosis and cell cycle arrest.  

PubMed

The natural product gambogic acid (GA) has been demonstrated to be a promising chemotherapeutic drug for some cancers because of its ability to induce apoptosis and cell cycle arrest. Until now, no studies have looked at the role of GA in osteosarcoma. In this study, we observed the effects of GA on the growth and apoptosis of osteosarcoma cells in vitro. We found that GA treatment inhibits the proliferation of osteosarcoma cells by inducing cell cycle arrest. Moreover, we found that GA induces apoptosis in MG63, HOS and U2OS cells. Furthermore, we showed that GA treatment elevates the Bax/Bcl-2 ratio. GA mediated the G0/G1 phase arrest in U2OS cells; this arrest was associated with a decrease in phospho-GSK3-? (Ser9) and the expression of cyclin D1. Similarly, in MG63 cells, GA mediated G2/M cell cycle arrest, which was associated with a decrease in phospho-cdc2 (Thr 161) and cdc25B. Overall, our findings suggest that GA may be an effective anti-osteosarcoma drug because of its capability to inhibit proliferation and induce apoptosis of osteosarcoma cells. PMID:21331449

Zhao, Wei; Zhou, Shi-Feng; Zhang, Zhi-Peng; Xu, Gong-Ping; Li, Xiao-Bo; Yan, Jing-Long

2011-05-01

67

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

68

Retinoic acids induce growth inhibition and apoptosis in adult T-cell leukemia (ATL) cell lines  

Microsoft Academic Search

Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). Despite the administration of combined intensive chemotherapy, the reported survival time of patients with acute and lymphoma types of ATL is less than 10 months. We therefore examine the effects of all-trans-retinoic acid (ATRA), 9-cis-RA and 13-cis-RA and tried to elucidate the

Satoshi Fujimura; Junji Suzumiya; Keizo Anzai; Kumiko Ohkubo; Tomoko Hata; Yasuaki Yamada; Shimeru Kamihira; Masahiro Kikuchi; Junko Ono

1998-01-01

69

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

70

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

SciTech Connect

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

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

2013-01-01

71

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

PubMed

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

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

2014-06-15

72

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

73

Inhibition of myeloma cell growth by all-trans retinoic acid is associated with upregulation of p21WAF1 and dephosphorylation of the retinoblastoma protein.  

PubMed

Retinoic acid and dexamethasone, in combination, inhibit the growth of human myeloma cell lines in a synergistic manner. Previously, we observed that all-trans retinoic acid (ATRA) caused G1 arrest and inhibited clonogenic growth of the OPM-2 human myeloma cell line. This was associated with downregulation of the IL-6 receptor (IL-6R) gp80 protein, while autocrine IL-6 production and gp130 were not affected. Growth inhibition was not reversed by the addition of exogenous IL-6 or forced, constitutive expression of the IL-6 receptor gp80 protein, suggesting that the mechanism of action of ATRA may be due to effects on the post-receptor pathway. Therefore, in this study we have investigated whether growth arrest was associated with changes in the level of phosphorylation of the RB protein. ATRA decreased the level of phosphorylation of the RB protein at doses > 5 x 10(-9) M and also induced a five fold increase in p21WAF1, while levels of p27KIP1 and CDK2 were unchanged. The ATRA-mediated increase in p21 preceded the change in RB phosphorylation and G1 arrest and was not reversed by the addition of exogenous IL-6. The levels of CDK2 activity were inhibited approximately 60% in ATRA-treated cells, suggesting that the increased p21 levels were sufficient to inhibit CDK activity and cause RB hypophosphorylation. Increased levels of p21 have recently been observed in human myeloma cells exposed to dexamethasone, and we suggest that the common ability of these two agents to inhibit myeloma cell growth depends on their induction of p21. PMID:10706449

Lavelle, D; Chen, Y H; Hankewych, M; Desimone, J

1999-10-01

74

Diterpene acids as larval growth inhibitors  

Microsoft Academic Search

Summary Kaurenoic and trachylobanoic acids from sunflower inhibited larval development in several Lepidoptera species. The tricyclic resin acids were also effective in curtailing growth ofPectinophora gossypiella and either reduction to carbinol or esterification of the carboxyl group lowered activity. Partial reversal of growth inhibition in the presence of relatively large amounts of cholesterol suggests an interaction with the insects' hormonal

C. A. Elliger; D. F. Zinkel; B. G. Chan; A. C. Waiss

1976-01-01

75

High temperature stimulates acetic acid accumulation and enhances the growth inhibition and ethanol production by Saccharomyces cerevisiae under fermenting conditions.  

PubMed

Cellular responses of Saccharomyces cerevisiae to high temperatures of up to 42 °C during ethanol fermentation at a high glucose concentration (i.e., 100 g/L) were investigated. Increased temperature correlated with stimulated glucose uptake to produce not only the thermal protectant glycerol but also ethanol and acetic acid. Carbon flux into the tricarboxylic acid (TCA) cycle correlated positively with cultivation temperature. These results indicate that the increased demand for energy (in the form of ATP), most likely caused by multiple stressors, including heat, acetic acid, and ethanol, was matched by both the fermentation and respiration pathways. Notably, acetic acid production was substantially stimulated compared to that of other metabolites during growth at increased temperature. The acetic acid produced in addition to ethanol seemed to subsequently result in adverse effects, leading to increased production of reactive oxygen species. This, in turn, appeared to cause the specific growth rate, and glucose uptake rate reduced leading to a decrease of the specific ethanol production rate far before glucose depletion. These results suggest that adverse effects from heat, acetic acid, ethanol, and oxidative stressors are synergistic, resulting in a decrease of the specific growth rate and ethanol production rate and, hence, are major determinants of cell stability and ethanol fermentation performance of S. cerevisiae at high temperatures. The results are discussed in the context of possible applications. PMID:24706214

Woo, Ji-Min; Yang, Kyung-Mi; Kim, Sae-Um; Blank, Lars M; Park, Jin-Byung

2014-07-01

76

Growth inhibition by caffeic acid, one of the phenolic constituents of honey, in HCT 15 colon cancer cells.  

PubMed

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

Jaganathan, Saravana Kumar

2012-01-01

77

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

PubMed

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

Hernández, Iker; Munné-Bosch, Sergi

2012-12-01

78

Antifolate drug interactions: enhancement of growth inhibition due to the antipurine 5,10-dideazatetrahydrofolic acid by the lipophilic dihydrofolate reductase inhibitors metoprine and trimetrexate.  

PubMed

The presence of low concentrations of the lipophilic dihydrofolate reductase inhibitors metoprine or trimetrexate, which cause little inhibition in the growth of cultured hepatoma cells in combination with weakly inhibiting concentrations of 5,10-dideazatetrahydrofolate, exhibit greater activity than would be predicted by the activity of the individual components. Growth inhibition by this inhibitor of glycineaminoribonucleotide transferase alone or in the presence of the reductase inhibitors is prevented by hypoxanthine indicating that the combination of drugs is enhancing the activity of 5,10-dideazatetrahydrofolate against purine biosynthesis. H35 hepatoma cells resistant to methotrexate (100-fold) as a result of a transport defect are 40-fold resistant to 5,10-dideazatetrahydrofolate suggesting that this analogue enters hepatoma cells at least in part by the reduced folate coenzyme-methotrexate transport system. The transport-resistant cells are also susceptible to enhanced inhibition of cell growth by low levels of reductase inhibitors in combination with 5,10-dideazatetrahydrofolate. These results have a corollary in an earlier study showing that the same concentrations of metoprine and trimetrexate could enhance the growth inhibition and cytotoxicity of the folate-based inhibitor of thymidylate synthase, 10-propargyl-5,8-dideazafolic acid (Galivan et al., Cancer Res., 47: 5256-5260, 1987). Combinations of 5,10-dideazatetrahydrofolic acid and 10-propargyl-5,8-dideazafolic acid are less growth inhibitory than that predicted by each of the folate analogues alone. It is possible that the effects of all these combinations are related to distortions in the folate pools caused by the folate analogues being used in combination. Two methods of analysis, one graphical and one mathematical, were used to analyze the drug interactions described in this presentation. The enhancement effect seen with the lipophilic dihydrofolate reductase inhibitors and 5,10-dideazatetrahydrofolate clearly represents a supraadditive or a synergistic drug interaction. In contrast the combination of the folate-based inhibitors of purine (5,10-dideazatetrahydrofolic acid) and thymidylate biosynthesis (N10-propargyl-5,8-dideazafolate) exhibit frank antagonism under certain conditions. PMID:2965613

Galivan, J; Nimec, Z; Rhee, M; Boschelli, D; Oronsky, A L; Kerwar, S S

1988-05-01

79

Inhibition of myeloma cell growth by dexamethasone and all-trans retinoic acid: synergy through modulation of interleukin-6 autocrine loop at multiple sites.  

PubMed

Interleukin-6 (IL-6)/IL-6 receptor (IL-6R) plays a major role in autocrine/paracrine growth regulation of myeloma cells. We investigated the effect of dexamethasone and all-trans retinoic acid, previously shown to modulate IL-6/IL-6R, on the in vitro growth of a human myeloma cell line, OPM-2. Both agents inhibited the clonogenic growth and 3H-thymidine incorporation in a concentration-dependent fashion. Isobologram and median effect analysis showed a strong synergy between these two agents with a combination index in the range of 0.2 to 0.6. Both agents decreased the labeling index and the cell fraction in S and G2/M phases, suggesting a block in G1-S phase transition. The clonogenic growth was stimulated by exogenous IL-6 and was inhibited by monoclonal antibody to IL-6, suggesting an autocrine function of IL-6. The effect of dexamethasone but not all-trans retinoic acid was completely reversed by exogenous IL-6. Dexamethasone increased, while all-trans retinoic acid reduced, IL-6R but not gp130 mRNA expression. Their combination caused a net reduction in IL-6R mRNA. Cellular IL-6R density was altered correspondingly without changes in the binding affinity. IL-6 mRNA expression was reduced by dexamethasone and the combination, but was not affected by retinoic acid alone. However, IL-6 secretion into culture supernatant was abolished by both agents. A survey of 4 additional human myeloma cells showed that 1 was sensitive to both, 1 was sensitive to one agent only, and 2 were resistant to both. The study demonstrates the possibility of regulating myeloma cell growth through modulation of IL-6/IL-6R autocrine/paracrine loop and the principle of achieving a synergistic effect by blocking this loop at multiple sites. PMID:8547658

Chen, Y H; Desai, P; Shiao, R T; Lavelle, D; Haleem, A; Chen, J

1996-01-01

80

Gamma-interferon-induced inhibition of the growth of Rickettsia prowazekii in fibroblasts cannot be explained by the degradation of tryptophan or other amino acids.  

PubMed Central

We examined the role of amino acid deprivation in gamma-interferon-induced (IFN-gamma) suppression of the growth of Rickettsia prowazekii in mouse L929 cells and human fibroblasts by measuring the amino acid pools in untreated and IFN-gamma-treated cells. In recombinant IFN-gamma-treated cultures of human fibroblasts, tryptophan was undetectable in both the intracellular pool and the extracellular medium. In contrast, tryptophan was not depleted from the intracellular pool or the extracellular medium of L929 cells treated with recombinant IFN-gamma or crude mouse lymphokines. None of the other amino acids measured was severely depleted in IFN-gamma-treated L929 cells and human fibroblasts. Extracts prepared from IFN-gamma-treated human fibroblasts exhibited indoleamine 2,3-dioxygenase activity, converting tryptophan into products that cochromatographed with N-formylkynurenine and kynurenine; however, extracts prepared from untreated human fibroblasts, untreated L929 cells, recombinant IFN-gamma-treated L929 cells, and mouse lymphokine-treated L929 cells did not degrade tryptophan. Human HeLa cells resembled the human fibroblasts in that they degraded tryptophan after IFN-gamma treatment. Similarly, mouse 3T3-A31 cells and mouse embryo fibroblasts resembled mouse L929 cells in that they did not degrade tryptophan. Supplementation of the extracellular medium with additional tryptophan reconstituted the tryptophan pool in mock-infected and R. prowazekii-infected, X-irradiated, IFN-gamma-treated human fibroblasts to values greater than those observed in untreated control cultures. However, reconstitution of the tryptophan pool did not relieve IFN-gamma-induced inhibition of rickettsial growth. Addition of kynurenine or N-formylkynurenine to rickettsia-infected human fibroblasts at concentrations four times the usual tryptophan concentration did not inhibit growth of R. prowazekii. We conclude that neither tryptophan depletion nor depletion of the other amino acids studied explains the inhibitory effect of IFN-gamma on rickettsial growth in mouse L929 cells. In IFN-gamma-treated human fibroblasts, either tryptophan depletion is not involved in the inhibition of rickettsial growth or tryptophan depletion and some other mechanism(s) together contribute to the inhibition of rickettsial growth.

Turco, J; Winkler, H H

1986-01-01

81

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

PubMed

Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2'-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E2 (PGE2) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B4 (LTB4). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser(241)), phospho-Akt (Thr(308)), phospho-Bad (Ser(136)), and Bcl-xL expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE2, LTB4 and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr(308)). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. PMID:23747687

Li, Ying; Zhao, Haixia; Wang, Yuzhong; Zheng, Hao; Yu, Wei; Chai, Hongyan; Zhang, Jing; Falck, John R; Guo, Austin M; Yue, Jiang; Peng, Renxiu; Yang, Jing

2013-10-01

82

18:1 n7 fatty acids inhibit growth and decrease inositol phosphate release in HT29 cells compared to n9 fatty acids  

Microsoft Academic Search

Studies have shown that trans fatty acids may play a role in the development of chronic diseases such as heart disease and cancer. The objective of the present project was to examine the effect of supplementation with 18:1 isomers, both positional and geometrical, as compared to 18:0 on the growth, membrane fatty acid composition and the phosphoinositide cycle of HT-29

Atif B. Awad; Tracy Herrmann; Carol S. Fink; Peter J. Horvath

1995-01-01

83

The nonsteroidal anti-inflammatory drug tolfenamic acid inhibits BT474 and SKBR3 breast cancer cell and tumor growth by repressing erbB2 expression.  

PubMed

Tolfenamic acid (TA) is a nonsteroidal 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 down-regulation of erbB2 but not Sp proteins. TA-induced erbB2 down-regulation 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. PMID:19435870

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

2009-05-01

84

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

85

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

PubMed Central

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

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

2013-01-01

86

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

PubMed Central

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

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

2013-01-01

87

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

PubMed

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

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

2014-07-01

88

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

PubMed

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

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

2009-05-01

89

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

90

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

PubMed

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

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

2012-05-01

91

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

92

Tolfenamic acid induces apoptosis and growth inhibition in head and neck cancer: involvement of NAG-1 expression.  

PubMed

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 expression in this induction. TA reduced head and neck cancer cell viability in a dose-dependent manner and induced apoptosis. The induced apoptosis was coincident with the expression of NAG-1. Overexpression of NAG-1 enhanced the apoptotic effect of TA, whereas suppression of NAG-1 expression by small interfering RNA attenuated TA-induced apoptosis. TA significantly inhibited tumor formation as assessed by xenograft models, and this result accompanied the induction of apoptotic cells and NAG-1 expression in tumor tissue samples. Taken together, these results demonstrate that TA induces apoptosis via NAG-1 expression in head and neck squamous cell carcinoma, providing an additional mechanistic explanation for the apoptotic activity of TA. PMID:22536345

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

2012-01-01

93

Tolfenamic Acid Induces Apoptosis and Growth Inhibition in Head and Neck Cancer: Involvement of NAG-1 Expression  

PubMed Central

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 expression in this induction. TA reduced head and neck cancer cell viability in a dose-dependent manner and induced apoptosis. The induced apoptosis was coincident with the expression of NAG-1. Overexpression of NAG-1 enhanced the apoptotic effect of TA, whereas suppression of NAG-1 expression by small interfering RNA attenuated TA-induced apoptosis. TA significantly inhibited tumor formation as assessed by xenograft models, and this result accompanied the induction of apoptotic cells and NAG-1 expression in tumor tissue samples. Taken together, these results demonstrate that TA induces apoptosis via NAG-1 expression in head and neck squamous cell carcinoma, providing an additional mechanistic explanation for the apoptotic activity of TA.

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

2012-01-01

94

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

SciTech Connect

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

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

2013-08-02

95

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

96

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

PubMed Central

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

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

2014-01-01

97

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

PubMed

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

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

2010-06-01

98

Combination Effects of Salvianolic Acid B with Low Dose Celecoxib on Inhibition of Head and Neck Squamous Cell Carcinoma Growth in vitro and in vivo  

PubMed Central

Head and neck squamous cell carcinoma (HNSCC) development is closely associated with inflammation. Cyclooxygenase-2 (Cox-2) is an important mediator of inflammation. Therefore, celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long term use of celecoxib, but it appears likely that this may be diminished by lowering its dose. We found that salvianolic acid B (Sal-B), isolated from Salvia miltiorrhiza Bge, can effectively suppress COX-2 expression and induce apoptosis in a variety of cancer cell lines. In this study, we report that combination of Sal-B with low dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. The combination effects were assessed in four HNSCC cell lines (JHU-06, -011, -013 and -022) by evaluating cell viability, proliferation, and tumor xenograft growth. Cell viability and proliferation were significantly inhibited by both the combined and single agent treatments. However, the combination treatment significantly enhanced anticancer efficacy in JHU-013 and JHU-022 cell lines compared to the single treatment regimens. A half dose of daily Sal-B (40mg/kg/day) and celecoxib (2.5mg/kg/day) significantly inhibited JHU-013 xenograft growth, relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was not only associated with profound inhibition of COX-2, and enhanced induction of apoptosis. Taken together, these results strongly suggest that combination of Sal-B, a multifunctional anticancer agent, with low dose of celecoxib hold potential as a new preventive strategy in targeting inflammatory associated tumor development.

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

2010-01-01

99

Secreted Protein Acidic and Rich in Cysteine (SPARC) Inhibits Integrin-Mediated Adhesion and Growth Factor-Dependent Survival Signaling in Ovarian Cancer  

PubMed Central

The matricellular glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been accorded major roles in regulation of cell adhesion and proliferation, as well as tumorigenesis and metastasis. We have recently reported that in addition to its potent antiproliferative and proapoptotic functions, SPARC also abrogates ovarian carcinoma cell adhesion, a key step in peritoneal implantation. However, the underlying molecular mechanism through which SPARC ameliorates peritoneal ovarian carcinomatosis seems to be multifaceted and has yet to be delineated. Herein, we show that SPARC significantly inhibited integrin-mediated ovarian cancer cell adhesion to extracellular matrix proteins, as well as to peritoneal mesothelial cells. This counteradhesive effect of SPARC was shown to be mediated in part through significant attenuation of cell surface expression and clustering of ?v-integrin subunit, ?v?3- and ?v?5-heterodimers, and ?1-subunit, albeit to a lesser extent, in ovarian cancer cells. Moreover, SPARC significantly suppressed both anchorage-dependent and -independent activation of AKT and mitogen-acti-vated protein kinase survival signaling pathways in ovarian cancer cells in response to serum and epidermal growth factor stimulation. In summary, we have identified a novel role of SPARC as a negative regulator of both integrin-mediated adhesion and growth factor-stimulated survival signaling pathways in ovarian cancer.

Said, Neveen; Najwer, Ida; Motamed, Kouros

2007-01-01

100

Kynurenic acid inhibits the release of the neurotrophic fibroblast growth factor (FGF)-1 and enhances proliferation of glia cells, in vitro.  

PubMed

1. Kynurenic (KYNA) and quinolinic (QUIN) acids are neuroactive tryptophan metabolites formed along the kynurenine pathway: the first is considered a non-competitive antagonist and the second an agonist of glutamate receptors of NMDA type. The affinity of these compounds for glutamate receptors is, however, relatively low and does not explain KYNA neuroprotective actions in models of post-ischemic brain damage. 2. We evaluated KYNA effects on the release of fibroblast growth factor (FGF)-1, a potent neurotrophic cytokine. Because KYNA exhibits a neuroprotective profile in vitro and in vivo, we anticipated that it could function as an autocrine/paracrine inducer of FGF-1 release. Studies were performed in several models of FGF-1 secretion (FGF-1 transfected NIH 3T3 cells exposed to heat shock, A375 melanoma cells exposed to serum starvation, growth factor deprived human endothelial cells). To our surprise, KYNA, at low concentration, inhibited FGF-1 release in all cellular models. QUIN, a compound having opposite effects on glutamate receptors, also reduced this release, but its potency was significantly lower than that of KYNA. 3. KYNA and QUIN also displayed a major stimulatory effect on the proliferation rate of mouse microglia and human glioblastoma cells, in vitro. 4. Our data suggest that minor changes of local KYNA concentration may modulate FGF-1 release, cell proliferation, and ultimately tissue damage in different pathological conditions. PMID:16392031

Di Serio, Claudia; Cozzi, Andrea; Angeli, Ilaria; Doria, Laura; Micucci, Isabella; Pellerito, Silvia; Mirone, Patrizia; Masotti, Giulio; Moroni, Flavio; Tarantini, Francesca

2005-09-01

101

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

102

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

2013-02-01

103

STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION  

PubMed Central

A simplified and compact agitator for growth inhibition tests with serum-leucocyte mixtures has been described. Several modifications have been made as well in the technique of the test, which have eliminated occasional irregularities that necessitated discarding the results of the individual experiment. Such irregularities were found to be due chiefly to injury of the pneumococci brought about by prolonged suspension in gelatin-Locke's solution which resulted in failure of the organisms to grow in the control serum-leucocyte tubes. This deterioration of the pneumococcus suspension may be greatly lessened or entirely prevented by the addition of a small quantity of a balanced phosphate mixture to the gelatin-Locke's solution. The use of small tubes made of Pyrex glass has also eliminated the former, not infrequent, occurrence of early hemolysis which was sometimes intense enough to disturb the results of the test. It has been found that washed rabbit leucocytes, suspended in their homologous serum, may be kept in the ice box for as long a period as 2 days without showing any apparent diminution of their functional activity in the serum-leucocyte test.

Robertson, Oswald H.; Woo, Shutai T.; Cheer, Sheo Nan

1924-01-01

104

Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic mice.  

PubMed

The nonsteroidal anti-inflammatory drug (NSAID), tolfenamic acid (TA) is emerging as a new anti-cancer agent. TA induces the degradation of specific Specificity protein (Sp) transcription factors, Sp1, Sp3 and Sp4 which are associated with tumor growth and metastasis. In this study we have evaluated the effect of TA on lung cancer using both in vitro and in vivo models. TA in a dose dependent manner inhibited proliferation and cell viability of two different lung cancer cells, A549 and CRL5803. TA treatment for 48 h significantly decreased the expression of Sp1, Sp3 and Sp4. The hepatocyte growth factor receptor, c-Met is overexpressed in a variety of cancers including lung cancer and Sp proteins mediate the regulation of c-Met. TA diminished the expression of c-Met protein and modulates its downstream signaling pathway. Furthermore, TA treatment significantly increased the number of apoptotic cells and pro-apoptotic markers c-PARP and Bax confirming the activation of apoptotic pathways. In vivo studies using the orthotopic mice model for lung cancer showed that TA (25 mg/kg/2 days and 50 mg/kg/2 days) resulted in a dose dependent decrease in tumor formation. The immunohistochemical staining of lung tissue showed high expression of Sp1, Sp3, Sp4, c-Met and phospho Met in control group and a dose dependent decrease in TA treated groups. The crucial findings of this study support that targeting c-Met with a potent inhibitor of Sp proteins is a robust strategy for the implications in lung cancer treatment and TA can serve as a therapeutic agent for this devastating disease. PMID:19851711

Colon, Jimmie; Basha, Md Riyaz; Madero-Visbal, Rafael; Konduri, Santhi; Baker, Cheryl H; Herrera, Luis J; Safe, Stephen; Sheikh-Hamad, David; Abudayyeh, Ala; Alvarado, Beatrice; Abdelrahim, Maen

2011-02-01

105

C6-ceramide and targeted inhibition of acid ceramidase induce synergistic decreases in breast cancer cell growth.  

PubMed

The sphingolipid ceramide is known to play a central role in chemo- and radiation-induced cell death. Acid ceramidase (AC) hydrolyzes ceramide, and thus reduces intracellular levels of this proapoptotic lipid. The role of AC as a putative anticancer target is supported by reports of upregulation in prostate cancer and in some breast tumors. In this study, we determined whether the introduction of an AC inhibitor would enhance the apoptosis-inducing effects of C6-ceramide (C6-cer) in breast cancer cells. Cultured breast cancer cells were treated with DM102 [(2R,3Z)-N-(1-hydroxyoctadec-3-en-2-yl)pivalamide, C6-cer, or the combination. Cell viability and cytotoxic synergy were assessed. Activation of apoptotic pathways, generation of reactive oxygen species, and mitochondrial transmembrane potential were determined. DM102 was a more effective AC inhibitor than N-oleoylethanolamine (NOE) and (1R,2R)-2-N-(tetradecanoylamino)-1-(4'-nitrophenyl)-1,3-propandiol (B-13) in MDA-MB-231, MCF-7, and BT-474 cells. As single agents, C6-cer (IC(50) 5-10 ?M) and DM102 (IC(50) 20 ?M) were only moderately cytotoxic in MDA-MB-231, MCF-7, and SK-BR-3 cells. Co-administration, however, produced synergistic decreases in viability (combination index <0.5) in all cell lines. Apoptosis was confirmed in MDA-MB-231 cells by detection of caspase 3 cleavage and a >3-fold increase in caspase 3/7 activation, PARP cleavage, and a >70% increase in Annexin-V positive cells. C6-cer/DM102 increased ROS levels 4-fold in MDA-MB-231 cells, shifted the ratio of Bax:Bcl-2 to >9-fold that of control cells, and resulted in mitochondrial membrane depolarization. DM102 also increased the synthesis of (3)H-palmitate-labeled long-chain ceramides by 2-fold when C6-cer was present. These data support the effectiveness of targeting AC in combination with exogenous short-chain ceramide as an anticancer strategy, and warrant continued investigation into the utility of the C6-cer/DM102 drug duo in human breast cancer. PMID:21935601

Flowers, Margaret; Fabriás, Gemma; Delgado, Antonio; Casas, Josefina; Abad, Jose Luis; Cabot, Myles C

2012-06-01

106

Exocarpic acid inhibits mycolic acid biosynthesis in Mycobacterium tuberculosis.  

PubMed

Exocarpic acid (13 E-octadecene-9,11-diynoic acid) from Exocarpos latifolius R.Br. (Santalaceae) was previously shown to have specific antimycobacterial activity. Microarray data suggested inhibition of fatty acid metabolism as a potential mode of action. Experiments designed to elucidate the mechanism of action showed that exocarpic acid was effective at inhibition of mycolic acid biosynthesis and did not act by dissipating the proton gradient in treated M. tuberculosis. Amide derivatives of exocarpic acid displayed similar properties to exocarpic acid, while other polyacetylenic fatty acids varied in their effects on mycolic acid biosynthesis. PMID:20506078

Koch, Michael; Bugni, Tim S; Sondossi, Mohammad; Ireland, Chris M; Barrows, Louis R

2010-10-01

107

Retinoic acid suppresses growth of lesions, inhibits peritoneal cytokine secretion, and promotes macrophage differentiation in an immunocompetent mouse model of endometriosis  

PubMed Central

Objective To determine the effects of retinoic acid (RA) on establishment and growth of endometrial lesions, peritoneal IL-6 and MCP-1 concentrations, and CD38, CD11b, F4/80 expression on peritoneal macrophages in an immunocompetent mouse model of endometriosis. Design Experimental transplantation study using mice. Setting Academic medical center. Animals C57BL/6 recipient mice and syngeneic Green Fluorescent Protein transgenic (GFP+) mice. Intervention(s) Recipient mice were inoculated with GFP+ minced uterine tissue to induce endometriosis and treated with RA (400 nmol/day) or vehicle for 17 days (3 days before to 14 days after tissue injection). Main Outcome Measure(s) Total number of GFP+ implants in recipient mice, number of implants showing visible blood vessels, total volume of established lesions per mouse, concentrations of IL-6 and MCP-1 in peritoneal fluid, expression of CD11b, F4/80 and CD38 on peritoneal macrophages. Results 17 days of RA treatment reduced the number of implants versus controls and decreased the frequency of lesions with vessels. Peritoneal washings in RA-treated animals had lower IL-6 and MCP-1 than controls 3 days after endometrial inoculation and lower levels of IL-6 on day 14 after inoculation. Concomitant with these effects on day 14, CD38, CD11b, and F4/80 were higher on macrophages from RA-treated mice vs. controls. Conclusions RA inhibits the development of endometriotic implants. This effect may be caused, at least in part, by reduced IL-6 and MCP-1 production and enhanced differentiation of peritoneal macrophages.

Wieser, Friedrich; Wu, Juanjuan; Shen, Zhaoju; Taylor, Robert N.; Sidell, Neil

2012-01-01

108

Caffeic acid phenethyl ester induces E2F-1-mediated growth inhibition and cell-cycle arrest in human cervical cancer cells.  

PubMed

Caffeic acid phenyl ester (CAPE) has been identified as an active component of propolis, a substance that confers diverse activities in cells of various origins. However, the molecular basis of CAPE-mediated cellular activity remains to be clarified. Here, we show that CAPE preferentially induced S- and G2 /M-phase cell-cycle arrests and initiated apoptosis in human cervical cancer lines. The effect was found to be associated with increased expression of E2F-1, as there is no CAPE-mediated induction of E2F-1 in the pre-cancerous cervical Z172 cells. CAPE also up-regulated the E2F-1 target genes cyclin A, cyclin E and apoptotic protease activating of factor 1 (Apaf-1) but down-regulated cyclin B and induced myeloid leukemia cell differentiation protein (Mcl-1). These results suggest the involvement of E2F-1 in CAPE-mediated growth inhibition and cell-cycle arrest. Transient transfection studies with luciferase reporters revealed that CAPE altered the transcriptional activity of the apaf-1 and mcl-1 promoters. Further studies using chromatin immunoprecipitation assays demonstrated that E2F-1 binding to the apaf-1 and cyclin B promoters was increased and decreased, respectively, in CAPE-treated cells. Furthermore, E2F-1 silencing abolished CAPE-mediated effects on cell-cycle arrest, apoptosis and related gene expression. Taken together, these results indicate a crucial role for E2F-1 in CAPE-mediated cellular activities in cervical cancer cells. PMID:23497083

Hsu, Tzu-Hui; Chu, Chin-Chen; Hung, Mei-Whey; Lee, Hwei-Jen; Hsu, Hsien-Jun; Chang, Tsu-Chung

2013-06-01

109

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

110

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

111

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

SciTech Connect

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

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

2012-04-15

112

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

113

Method of Cell Growth Inhibition with Agnoprotein.  

National Technical Information Service (NTIS)

The growth of normal and abnormally proliferating cells can be inhibited by the introduction of agnoprotein, or biologically active fragments or derivatives of agnoprotein, into the cell in the absence of any other polyoma virus protein or viral replicati...

K. Khalili

2003-01-01

114

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

115

Growth Hormone Release Inhibiting Hormone in Acromegaly  

Microsoft Academic Search

Growth hormone release inhibiting hormone (GHRIH) was administered by constant infusion over 75 minutes to eight acromegalic patients at different doses. 100 to 1,000 ?g were equally effective in reducing circulating growth hormone (GH) levels; 25 ?g lowered GH levels in only five patients, and at this dose the extent of the fall was smaller than from doses of 100

G. M. Besser; C. H. Mortimer; D. Carr; A. V. Schally; D. H. Coy; D. Evered; A. J. Kastin; W. M. G. Tunbridge; M. O. Thorner; R. Hall

1974-01-01

116

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

PubMed

Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p<0.01). A more pronounced decrease (23-27%, p<0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p<0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p<0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. PMID:22366264

van Heumen, Bjorn W H; Roelofs, Hennie M J; Te Morsche, René H M; Marian, Brigitte; Nagengast, Fokko M; Peters, Wilbert H M

2012-04-15

117

Growth of Transplastomic Cells Expressing d-Amino Acid Oxidase in Chloroplasts Is Tolerant to d-Alanine and Inhibited by d-Valine1[W][OA  

PubMed Central

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

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

2012-01-01

118

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

119

Aliphatic fatty acids and esters: Inhibition of growth and exoenzyme production of Candida, and their cytotoxicity in vitro: Anti-Candida effect and cytotoxicity of fatty acids and esters.  

PubMed

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

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

2014-09-01

120

Inhibition of multiplication of herpes simplex virus by caffeic acid.  

PubMed

Hot water extracts of coffee grinds and commercial instant coffee solutions have been shown to exhibit marked antiviral and virucidal activities against herpes simplex virus type 1 (HSV-1). Specifically, it has been shown that caffeine and N-methyl-pyridinium formate inhibit the multiplication of HSV-1 in HEp-2 cells. The present study examined the virological properties and the antiviral activity of caffeic acid against HSV-1. Caffeic acid inhibited the multiplication of HSV-1 in vitro, while chlorogenic acid, a caffeic acid ester with quinic acid, did not. These reagents did not have a direct virucidal effect. The one-step growth curve of HSV-1 showed that the addition of caffeic acid at 8 h post infection (h p.i.) did not significantly affect the formation of progeny viruses. An analysis of the influence of the time of caffeic acid addition, revealed that addition at an early time post infection remarkably inhibited the formation of progeny infectious virus in the infected cells, but its addition after 6 h p.i. (i.e., the time of the completion of viral genome replication) did not efficiently inhibit this process. These results indicate that caffeic acid inhibits HSV-1 multiplication mainly before the completion of viral DNA replication, but not thereafter. Although caffeic acid showed some cytotoxicity by prolonged incubation, the observed antiviral activity is likely not the secondary result of the cytotoxic effect of the reagent, because the inhibition of the virus multiplication was observed before appearance of the notable cytotoxicity. PMID:21725588

Ikeda, Keiko; Tsujimoto, Kazuko; Uozaki, Misao; Nishide, Mitsunori; Suzuki, Yukiko; Koyama, A Hajime; Yamasaki, Hisashi

2011-10-01

121

Inhibition of phospholipase D by agents that inhibit cell growth.  

PubMed

The phospholipases are an important class of enzymes for growth factor and oncogene intracellular signalling. The anti-tumor drug suramin was found to inhibit phosphatidylcholine hydrolysis and trans-phosphatidylation by solubilized rat brain phospholipase D (PLD) with an IC50 of 15 microM. An azo analogue of suramin, which is a considerably more potent inhibitor of phosphatidylinositol phospholipase C (PIPLC) than suramin, inhibited PLD with and IC50 of 58 microM. D-609, a xanthogenate compound with in vitro antitumor activity, inhibited PLD with an IC50 of 820 microM. The cytotoxic aminosteroid compound U-73, 122 was a weaker inhibitor of PLD with an IC50 of 78 microM. However, U-73, 122 was a more potent inhibitor of PLD in fibroblast membranes with an IC50 of 25 microM, while suramin was less active with an IC50 of 4.2 mM. The antitumor ether lipid drug ET-18-OCH3 did not inhibit solubilized or membrane PLD although it is a potent inhibitor of PIPLC. The results of the study show that the compounds tested have different abilities to inhibit PIPLC and PLD. Access of hydrophilic drugs to membrane PLD may be a limiting factor to their inhibitory activity. PMID:8352550

Gratas, C; Powis, G

1993-01-01

122

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

123

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

2013-11-01

124

Menaquinone Analogs Inhibit Growth of Bacterial Pathogens  

PubMed Central

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

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

2013-01-01

125

Bacterial contact-dependent growth inhibition.  

PubMed

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

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

2013-05-01

126

Bacterial contact-dependent growth inhibition (CDI)  

PubMed Central

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

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

2013-01-01

127

Inhibition of tumour growth by lipoxygenase inhibitors.  

PubMed Central

The potential involvement of lipoxygenase metabolites in the tumour growth stimulatory activity of arachidonic and linoleic acid has been studied using the 5-lipoxygenase inhibitors, BWA4C, BWB70C and Zileuton. In vitro the former two agents were relatively potent inhibitors of growth of murine adenocarcinomas (MACs) with IC50 values < 10 microM, whereas Zileuton was less effective. In vivo studies showed BWA4C to be an effective inhibitor of the growth of both the MAC26 and MAC16 tumours at dose levels between 5 and 25 mg kg-1 (b.d.). The growth rate of the MAC26 tumour was also decreased by BWB70C at 25 mg kg-1, whereas lower doses were either ineffective or stimulated tumour growth. This differential effect of the 5-lipoxygenases inhibitors on tumour growth may arise from effects on the 12- and 15-lipoxygenase pathways. To quantify the effect cells were labelled with [3H]arachidonic acid and the biosynthesis of 5-, 12- and 15-hydroxyeicosatetraenoic acid (HETE) was analysed by high-performance liquid chromatography. All three agents caused a decrease in 5-HETE production, although the effect was less pronounced with Zileuton. In MAC26 cells both BWA4C and BWB70C caused a decrease in 12-HETE formation whereas Zileuton had no effect on the other lipoxygenase pathways. The inhibitory effect of these agents on cell growth may result from an imbalance of metabolism of arachidonic acid between the 5-, 12- and 15-lipoxygenase pathways.

Hussey, H. J.; Tisdale, M. J.

1996-01-01

128

Phytic Acid Inhibits Lipid Peroxidation In Vitro  

PubMed Central

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

Weglarz, Ludmila; Dzierzewicz, Zofia

2013-01-01

129

Boric acid inhibits human prostate cancer cell proliferation  

Microsoft Academic Search

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

Wade T. Barranco; Curtis D. Eckhert

2004-01-01

130

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

Microsoft Academic Search

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

Bayan M. Abu-Ghazaleh

2006-01-01

131

Use of natural materials for the inhibition of iron oxidizing bacteria involved in the generation of acid mine drainage  

Microsoft Academic Search

Obligate autotrophic and acidophilic characteristics of iron oxidizing bacteria were exploited in order to prevent or attenuate the generation of acid mine drainage. Inhibition of biomass growth was performed by variation of 9K medium by increasing ferrous iron concentration (substrate inhibition), by addition of limestone (inhibition by pH increase) and olive pomace (inhibition by organic compounds). Inhibition tests of batch

Francesca Pagnanelli; Marta Luigi; Sara Mainelli; Luigi Toro

2007-01-01

132

Understanding biocatalyst inhibition by carboxylic acids  

PubMed Central

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

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

2013-01-01

133

A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer.  

PubMed

Insulin-like growth factor (IGF)-mediated signaling is a newly recognized clinical target in prostate cancer, and it is hypothesized that blockade of the IGF receptor (IGF1R) will impair downstream signaling and slow tumor growth. In this study the efficacy of nordihydroguaiaretic acid (NDGA), a small molecule inhibitor of the IGF-1R, was prospectively evaluated in patients with non-metastatic hormone-sensitive prostate cancer (HSPC). Eligible patients had non-metastatic HSPC with a rising prostate-specific antigen (PSA) and a normal testosterone level. NDGA 2000 mg was given orally daily in 28 day cycles and treatment continued until PSA progression or toxicity. Accrual was stopped early after a pre-planned interim analysis showed no significant PSA declines after 3 cycles of treatment among the first 12 patients enrolled. Median time on treatment was 9 cycles (range 2-19) for 11 patients now off study; 1 patient continues to receive therapy and has been on study for 29 months. Seven patients experienced non-sustained declines in PSA ranging from 1.9 to 15.8% of baseline. PSADT lengthened by a median of 1.4 months for all evaluable patients when compared to pretreatment PSADT (range -6.1 to +19.8 months). Grade 3 events were rare and included nausea/vomiting, syncope due to dehydration, and elevated liver function tests in 1 patient, and cognitive disturbance in another patient. NDGA therapy lengthens median PSADT but does not induce significant PSA declines. Further study may require a placebo-control to determine if changes in PSADT are drug related. PMID:21971890

Friedlander, Terence W; Weinberg, Vivian K; Huang, Yong; Mi, Joanna T; Formaker, Carl G; Small, Eric J; Harzstark, Andrea L; Lin, Amy M; Fong, Lawrence; Ryan, Charles J

2012-01-01

134

Growth inhibition of a human myeloma cell line by all-trans retinoic acid is not mediated through downregulation of interleukin-6 receptors but through upregulation of p21(WAF1).  

PubMed

All-trans retinoic acid (ATRA) has previously been shown to inhibit the growth of OPM-2 human myeloma cells. The growth inhibition was postulated to result from a transcriptional downregulation of interleukin-6 receptor alpha (IL-6Ralpha) with IL-6Rbeta (gp130) unaffected. To formally test this hypothesis, an expression vector designed for constitutive IL-6Ralpha expression was constructed and used for transfection of OPM-2 cells. Six stable transfectants were cloned. The expression of IL-6Ralpha was shown by immunofluorescence with anti-IL-6Ralpha antibody and 125I-IL-6 binding. In five of six transfectant clones, cellular IL-6Ralpha was 1.5- to 6-fold higher than the parental cells, with the ligand binding affinity unchanged. While ATRA reduced IL-6Ralpha expression in the parental OPM-2 cells, it enhanced its expression in these five transfectants. The clonogenic growth of these transfectants, however, remained strongly inhibited by ATRA. Further analysis, comparing the parental OPM-2 cells and a representative transfectant, clone C5, showed that IL-6 caused rapid tyrosine phosphorylation of gp130 in both OPM-2 and C5 clones. Pretreatment with ATRA greatly reduced IL-6-induced gp130 phosphorylation in OPM-2 cells, reflecting a reduction in cellular IL-6Ralpha. In contrast, IL-6-induced gp130 phosphorylation was not reduced by ATRA pretreatment in C5 cells, indicating that the expressed IL-6Ralpha was functional. Similar to OPM-2 cells, C5 cells were sensitive to growth inhibition by dexamethasone, which was entirely reversed by exogenous IL-6, suggesting that the IL-6 postreceptor signal transduction remained intact. ATRA was further shown to upregulate p21(WAF1) expression and cause dephosphorylation of the retinoblastoma protein (pRB) in both OPM-2 and C5 cells. Exogenous IL-6 also failed to reverse these effects of ATRA. Thus, the growth inhibitory activity of ATRA is not mediated through cellular IL-6Ralpha downregulation and is likely to result from a direct upregulation of p21(WAF1) and consequent dephosphorylation of pRB. PMID:10381520

Chen, Y H; Lavelle, D; DeSimone, J; Uddin, S; Platanias, L C; Hankewych, M

1999-07-01

135

Growth Inhibition of Thermotolerant Yeast, Kluyveromyces marxianus, in Hydrolysates from Cassava Pulp.  

PubMed

In this study, we report the inhibition of Kluyveromyces marxianus TISTR5925 growth and ethanol fermentation in the presence of furan derivatives and weak acids (acetic acid and lactic acid) at high temperatures. Cassava pulp, obtained as the waste from starch processing, was collected from 14 starch factories located in several provinces of Thailand. At a high temperature (42 °C), the cassava pulp hydrolysate from some starch factories strongly inhibited growth and ethanol production of both K. marxianus (strain TISTR5925) and Saccharomyces cerevisiae (strain K3). HPLC detected high levels of lactic acid and acetic acid in the hydrolysates, suggesting that these weak acids impaired the growth of K. marxianus at high temperature. We isolated Trp-requiring mutants that had reduced tolerance to acetic acid compared to the wild-type. This sensitivity to acetic acid was suppressed by supplementation of the medium with tryptophan. PMID:24781978

Rugthaworn, Prapassorn; Murata, Yoshinori; Machida, Masashi; Apiwatanapiwat, Waraporn; Hirooka, Akiko; Thanapase, Warunee; Dangjarean, Hatairat; Ushiwaka, Satoru; Morimitsu, Kozo; Kosugi, Akihiko; Arai, Takamitsu; Vaithanomsat, Pilanee

2014-07-01

136

Boswellic acid inhibits expression of acid sphingomyelinase in intestinal cells  

PubMed Central

Background Boswellic acid is a type of triterpenoids with antiinflammatory and antiproliferative properties. Sphingomyelin metabolism generates multiple lipid signals affecting cell proliferation, inflammation, and apoptosis. Upregulation of acid sphingomyelinase (SMase) has been found in several inflammation-related diseases such as inflammatory bowel diseases, atherosclerosis, and diabetes. Methods The present study is to examine the effect of 3-acetyl-11-keto-?-boswellic acids (AKBA), a potent boswellic acid, on acid SMase activity and expression in intestinal cells. Both transformed Caco-2 cells and non-transformed Int407 cells were incubated with AKBA. After incubation, the change of acid SMase activity was assayed biochemically, the enzyme protein was examined by Western blot, and acid SMase mRNA was quantified by qPCR. Results We found that AKBA decreased acid SMase activity in both intestinal cell lines in dose and time dependent manners without affecting the secretion of the enzyme to the cell culture medium. The effect of AKBA was more effective in the fetal bovine serum-free culture medium. Among different types of boswellic acid, AKBA was the most potent one. The inhibitory effect on acid SMase activity occurred only in the intact cells but not in cell-free extract in the test tubes. At low concentration, AKBA only decreased the acid SMase activity but not the quantity of the enzyme protein. However, at high concentration, AKBA decreased both the mass of acid SMase protein and the mRNA levels of acid SMase in the cells, as demonstrated by Western blot and qPCR, respectively. Under the concentrations decreasing acid SMase activity, AKBA significantly inhibited cell proliferation. Conclusion We identified a novel inhibitory effect of boswellic acids on acid SMase expression, which may have implications in human diseases and health.

2009-01-01

137

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

PubMed

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

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

2013-04-15

138

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

139

Inhibition of mycobacterial growth by plumbagin derivatives.  

PubMed

Electron transport and respiratory pathways are active in both latent and rapidly growing mycobacteria and remain conserved in all mycobacterial species. In mycobacteria, menaquinone is the sole electron carrier responsible for electron transport. Menaquinone biosynthesis pathway is found to be essential for the growth of mycobacteria. Structural analogs of the substrate or product of this pathway are found to be inhibitory for the growth of Mycobacterium smegmatis and M. tuberculosis. Several plumbagin [5-hydroxy-2-methyl-1, 4-naphthaquinone] derivatives have been analyzed for their inhibitory effects of which butyrate plumbagin was found to be most effective on M. smegmatis mc(2)155, whereas crotonate plumbagin showed greater activity on M. tuberculosis H37Rv. Effect on electron transport and respiration was demonstrated by butyrate plumbagin inhibiting oxygen consumption in M. smegmatis. Structural modifications of these molecules can further be improved upon to generate new molecules against mycobacteria. PMID:20456370

Mathew, Ritta; Kruthiventi, Anil K; Prasad, Jalli V; Kumar, Sadula P; Srinu, Garlapati; Chatterji, Dipankar

2010-07-01

140

Bile acids affect the growth of human cholangiocarcinoma via NF-kB pathway.  

PubMed

We observed that free bile acids (CA, DCA, and CDCA) inhibited the growth of cholangiocarcinoma cells by promoting cell apoptosis, while the conjugated bile acids (GCA, GDCA, and GCDCA) stimulated cell growth. Consistently, we found that GDCA stimulated tumor growth and CDCA decreased tumor growth in xenografted mice. Further, the phosphorylated IkB was downregulated by free bile acids, and was upregulated by the conjugated bile acids. IL-6 and COX-2 were decreased by the free bile acids and increased by the conjugated bile acids. Collectively, these results suggest that the bile acids regulate the growth of cholangiocarcinoma by modulating NF-kB pathway. PMID:23362950

Dai, Jiaqi; Wang, Hongxia; Dong, Ying; Zhang, Yinxin; Wang, Jian

2013-02-01

141

Trans Retinoic Acid Enhances the Growth Response of Epidermal Keratinocytes to Epidermal Growth Factor and Transforming Growth Factor Beta  

Microsoft Academic Search

Retinoids have been shown to either stimulate or inhibit epidermal keratinocyte proliferation. We have observed that in serum and growth factor free medium (basal medium), epidermal growth factor (EGF) and transforming growth factor alpha (TGF?) stimulated DNA synthesis in mouse epidermal keratinocyte cultures (mKC) in a time- and dose-dependent manner. Incubation with all-trans retinoic acid (RA) greatly enhanced the stimulatory

Philip S. Tong; Nancy N. Horowitz; Larry A. Wheeler

1990-01-01

142

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

Microsoft Academic Search

Overexpression of cyclooxygenase-2 (COX-2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a nonsteroidal anti-inflam- matory drug, which inhibits COX-2 but not COX-1. This selective COX-2 inhibitor holds promise as a cancer preventive agent. Con- cerns about cardiotoxicity of celecoxib, limits its use in long-term chemoprevention and therapy. Salvianolic

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

2009-01-01

143

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

PubMed

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

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

2014-07-29

144

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

Microsoft Academic Search

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

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

2000-01-01

145

On the role of transforming growth factor-? in the growth inhibitory effects of retinoic acid in human pancreatic cancer cells  

PubMed Central

Background Retinoids are potent growth inhibitory and differentiating agents in a variety of cancer cell types. We have shown that retinoids induce growth arrest in all pancreatic cancer cell lines studied, regardless of their p53 and differentiation status. However, the mechanism of growth inhibition is not known. Since TGF-?2 is markedly induced by retinoids in other cancers and mediates MUC4 expression in pancreatic cancer cells, we investigated the role of TGF-? in retinoic acid-mediated growth inhibition in pancreatic cancer cells. Results Retinoic acid markedly inhibited proliferation of two cell lines (Capan-2 and Hs766T) in a concentration and time-dependent manner. Retinoic acid increased TGF-?2 mRNA content and secretion of the active and latent forms of TGF-?2 (measured by ELISA and bioassay). The concentrations of active and TGF-?2 secreted in response to 0.1 – 10 ?M retinoic acid were between 1–5 pM. TGF-?2 concentrations within this range also inhibited proliferation. A TGF-? neutralizing antibody blocked the growth inhibitory effects of retinoic acid in Capan-2 cells and partially inhibitory the effects in Hs766T cells. Conclusion These findings indicate that TGF-? can cause growth inhibition of pancreatic cancer cells, in a p53-independent manner. Furthermore, it demonstrates the fundamental role of TGF-? in growth inhibition in response to retinoic acid treatment is preserved in vitro.

Singh, Brahmchetna; Murphy, Richard F; Ding, Xian-Zhong; Roginsky, Alexandra B; Bell, Richard H; Adrian, Thomas E

2007-01-01

146

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

Microsoft Academic Search

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

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

1998-01-01

147

Rab7 prevents growth factor-independent survival by inhibiting cell-autonomous nutrient transporter expression.  

PubMed

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 glucose and amino acid transporter proteins from the cell surface. When Rab7 was inhibited, growth factor deprived cells maintained their mitochondrial membrane potential and displayed prolonged, growth factor-independent, nutrient-dependent cell survival. Thus, Rab7 functions as a proapoptotic protein by limiting cell-autonomous nutrient uptake. Consistent with this, dominant-negative Rab7 cooperated with E1A to promote the transformation of p53(-/-) mouse embryonic fibroblasts (MEFs). These results suggest that proteins that limit nutrient transporter expression function to prevent cell-autonomous growth and survival. PMID:14536059

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

2003-10-01

148

Ganoderic acid X, a lanostanoid triterpene, inhibits topoisomerases and induces apoptosis of cancer cells  

Microsoft Academic Search

Lanostanoid triterpenes isolated from Ganoderma amboinense were found to inhibit the growth of numerous cancer cell lines, and some of them inhibited the activities of topoisomerases I and II? in vitro. Among the bioactive isolates, one of the most potent triterpene was identified to be 3?-hydroxy-15?-acetoxy-lanosta-7,9(11),24-trien-26-oic acid, ganoderic acid X (GAX). Treatment of human hepatoma HuH-7 cells with GAX caused

Chyi-Hann Li; Pei-Yu Chen; Ue-Min Chang; Lou-Sing Kan; Woei-Horng Fang; Keh-Sung Tsai; Shwu-Bin Lin

2005-01-01

149

Inhibition of some polymorphonuclear leukocyte functions by ethacrynic acid.  

PubMed

Ethacrynic acid (10(-4) M) inhibits exocytosis, phagocytosis and superoxide release in rabbit polymorphonuclear leukocytes (PMN's). Dihydroethacrynic acid is a much weaker inhibitor of these PMN functions. Though ethacrynic acid inhibits ATPase activity in the PMN, this occur at much higher concentrations than required for inhibition of exocytosis and superoxide release, thus a causal relationship seems unlikely. The same applies to inhibition of ATP generation by ethacrynic acid: the concentration required to decrease ATP level in PMN's is much higher than required for the inhibitory effect on exocytosis. Inhibition of exocytosis by ethacrynic acid can be prevented by dithiothreitol. It is concluded that vulnerable sulfhydryl groups are involved in the inhibition by ethacrynic acid. PMID:6280731

Elferink, J G; Hoogendijk, A M; Riemersma, J C

1982-02-01

150

Auxin-induced sprout growth inhibition: Role of endogenous ethylene  

Microsoft Academic Search

The role of endogenous ethylene in auxin-mediated tuber sprout growth inhibition was determined in potato (Solanum tuberosum L. cv. Russet Burbank) minitubers. Treatment of tubers with biologically active auxins resulted in a transient, dose-dependent\\u000a increase in ethylene production and inhibition of sprout growth. Biologically inactive auxin analogs elicited neither response.\\u000a Continuous exposure to > 0.001 ?L L-1 exogenous ethylene inhibited

Jeffrey C. Suttle

2003-01-01

151

Fatty acid binding protein inhibits glycolithocholate sulfation.  

PubMed

Sulfation of hepatotoxic monohydroxy bile salts is viewed as an important detoxification mechanism. Bile salts are bound by fatty acid binding protein (FABP) with decreasing affinity as the extent of their hydroxylation increases. This binding has the potential to interfere with sulfation of monohydroxy bile salts and to augment their toxicity. FABP inhibits monohydroxy bile salt sulfation via bile salt sulfotransferases BST 1 and 2. With BST 1, the main BST, we obtained a maximal reduction of sulfation by 42.8 +/- 8.1%, using 10 microM glycolithocholate as substrate. FABP had no effect on sulfation of either 10 microM glycodeoxycholate or glycochenodeoxycholate. FABP may therefore specifically alter hepatotoxicity of lithocholate and its metabolites. PMID:1417875

Singer, S S; Dravis, D; Henkels, K; Trulzsch, D V

1992-07-01

152

Caffeic Acid Phenethyl Ester Causes p21Cip1 Induction, Akt Signaling Reduction, and Growth Inhibition in PC-3 Human Prostate Cancer Cells  

PubMed Central

Caffeic acid phenethyl ester (CAPE) treatment suppressed proliferation, colony formation, and cell cycle progression in PC-3 human prostate cancer cells. CAPE decreased protein expression of cyclin D1, cyclin E, SKP2, c-Myc, Akt1, Akt2, Akt3, total Akt, mTOR, Bcl-2, Rb, as well as phosphorylation of Rb, ERK1/2, Akt, mTOR, GSK3?, GSK3?, PDK1; but increased protein expression of KLF6 and p21Cip1. Microarray analysis indicated that pathways involved in cellular movement, cell death, proliferation, and cell cycle were affected by CAPE. Co-treatment of CAPE with chemotherapeutic drugs vinblastine, paclitaxol, and estramustine indicated synergistic suppression effect. CAPE administration may serve as a potential adjuvant therapy for prostate cancer.

Lin, Hui-Ping; Jiang, Shih Sheng; Chuu, Chih-Pin

2012-01-01

153

Aurin tricarboxylic acid inhibits experimental venous thrombosis.  

PubMed

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

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

1994-06-15

154

Myogenic differentiation triggered by antisense acidic fibroblast growth factor RNA.  

PubMed Central

Acidic fibroblast growth factor (FGF) and related family members regulate differentiation in organisms as diverse as Xenopus laevis and mammals. We utilized a well-characterized model of myogenic development to directly assess the importance of endogenously produced FGF in controlling differentiation. A role for endogenous FGF is suggested by the previous finding that acidic and basic FGF abundance in cultured myocytes decreases during differentiation. In this study we inhibited the endogenous production of FGF in murine Sol 8 myoblasts by using antisense RNA and observed precocious myogenic differentiation. Exogenously supplied acidic FGF rescues this phenotype. Further results suggest that the effect of FGF on myogenic differentiation is mediated in part through inhibition of myogenin expression. These results demonstrate a direct role for endogenously synthesized growth factors in regulating myogenesis and provide support for a general role for related proteins in mammalian development. Images

Fox, J C; Hsu, A Y; Swain, J L

1994-01-01

155

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

PubMed

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

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

2011-02-11

156

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

157

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

158

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

159

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

160

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

161

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

162

Ursodeoxycholate and tauroursodeoxycholate inhibit cholangiocyte growth and secretion of BDL rats through activation of PKC alpha  

Microsoft Academic Search

Accumulating bile acids (BA) trigger cholangiocyte proliferation in chronic cholestasis. The aim of this study was to determine if ursodeoxycholate (UDCA) or tauroursodeoxycholate (TUDCA) chronic feeding prevents the increased cholangiocyte growth and secretion in bile duct–ligated (BDL) rats, if UDCA and TUDCA effects are associated with increased cholangiocyte apoptosis, and to determine if this inhibition is dependent on increased intracellular

Gianfranco Alpini; Leonardo Baiocchi; Shannon Glaser; Yoshiyuki Ueno; Marco Marzioni; Heather Francis; Jo Lynne Phinizy; Mario Angelico; Gene LeSage

2002-01-01

163

Paraquat and nitrofurantoin inhibit growth of escherichia coli by inducing stringency  

Microsoft Academic Search

The herbicide paraquat and the antibiotic nitrofurantoin (redox?active compounds that can transfer electrons singly to oxygen) induced intracellular accumulation of the regulatory inhibitor guanosine tetraphosphate (stringency) in Escherichia coli. This mechanism is sufficient to account for the rapid bacteristasis produced in minimal medium by these agents. The growth inhibition and stringency induction were prevented by inclusion of specific amino acids

Richard L. Seither; Olen R. Brown

1984-01-01

164

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

165

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

2010-01-01

166

Light effects in yeast: inhibition by visible light of growth and transport in Saccharomyces cerevisiae grown at low temperatures.  

PubMed Central

Growth rate, sugar transport, and amino acid transport of yeast cells grown at 12 degrees C were inhibited by cool-white fluorescent light. At light intensities below 1,250 lx, growth and membrane transport were only slightly inhibited. Above 1,250 lx, there was increasing inhibition of both processes. Transport of histidine was completely inhibited after 3 to 5 days in cultures grown at 12 degrees C under 3,500-lx illumination. Cells grown at 20 degrees C were not inhibited by light intensities that caused complete loss of viability and membrane transport activity in cells grown at 12 degrees C.

Woodward, J R; Cirillo, V P; Edmunds, L N

1978-01-01

167

GRIM1, a Novel Growth Suppressor, Inhibits rRNA Maturation by Suppressing Small Nucleolar RNAs  

Microsoft Academic Search

We have recently isolated novel IFN-inducible gene, Gene associated with Retinoid-Interferon-induced Mortality-1 (GRIM-1), using a genetic technique. Moderate ectopic expression of GRIM-1 caused growth inhibition and sensitized cells to retinoic acid (RA)\\/IFN-induced cell death while high expression caused apoptosis. GRIM-1 depletion, using RNAi, conferred a growth advantage. Three protein isoforms (1?, 1? and 1?) with identical C-termini are produced from

Shreeram C. Nallar; Limei Lin; Varsha Srivastava; Padmaja Gade; Edward R. Hofmann; Hafiz Ahmed; Sekhar P. Reddy; Dhananjaya V. Kalvakolanu; Dhyan Chandra

2011-01-01

168

Targeted BCL2 inhibition effectively inhibits neuroblastoma tumour growth.  

PubMed

Genomic aberrations of key regulators of the apoptotic pathway have hardly been identified in neuroblastoma. We detected high BCL2 mRNA and protein levels in the majority of neuroblastoma tumours by Affymetrix expression profiling and Tissue Micro Array analysis. This BCL2 mRNA expression is strongly elevated compared to normal tissues and other malignancies. Most neuroblastoma cell lines lack this high BCL2 expression. Only two neuroblastoma cell lines (KCNR and SJNB12) show BCL2 expression levels representative for neuroblastoma tumours. To validate BCL2 as a therapeutic target in neuroblastoma we employed lentivirally mediated shRNA. Silencing of BCL2 in KCNR and SJNB12 resulted in massive apoptosis, while cell lines with low BCL2 expression were insensitive. Identical results were obtained by treatment of the neuroblastoma cell lines with the small molecule BCL2 inhibitor ABT263, which is currently being clinically evaluated. Combination assays of ABT263 with most classical cytostatics showed strong synergistic responses. Subcutaneous xenografts of a neuroblastoma cell line with high BCL2 expression in NMRI nu/nu mice showed a strong response to ABT263. These findings establish BCL2 as a promising drug target in neuroblastoma and warrant further evaluation of ABT263 and other BCL2 inhibiting drugs. PMID:22366560

Lamers, Fieke; Schild, Linda; den Hartog, Ilona J M; Ebus, Marli E; Westerhout, Ellen M; Ora, Ingrid; Koster, Jan; Versteeg, Rogier; Caron, Huib N; Molenaar, Jan J

2012-11-01

169

RGD-Tachyplesin Inhibits Tumor Growth1  

Microsoft Academic Search

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

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

2001-01-01

170

Mullerian Inhibiting Substance (MIS) Augments IFN-Gamma Mediated Inhibition of Breast Cancer Cell Growth.  

National Technical Information Service (NTIS)

Mullerian inhibiting Substance (MIS) is a member of the TGFbeta family, a class of molecules that govern a myriad of cellular processes including growth, differentiation, and apoptosis. In male embryos, MIS causes regression of the Mullerian duct. We have...

V. Gupta

2005-01-01

171

Novel Approaches to Inhibition of Gastric Acid Secretion  

PubMed Central

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

Shin, Jai Moo; Hunt, Richard

2010-01-01

172

Novel approaches to inhibition of gastric acid secretion.  

PubMed

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

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

2010-12-01

173

Timing of growth inhibition following shoot inversion in Pharbitis nil  

NASA Technical Reports Server (NTRS)

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

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

1989-01-01

174

Human Miillerian Inhibiting Substance Inhibits Tumor Growth in Vitro and in Vivo1  

Microsoft Academic Search

Mullerian inhibiting substance (MIS) causes regression of the miiller- ian duct in the male fetus. Bovine MIS has been reported to inhibit the growth of some gynecologicaltumors. Recombinant human MIS (rhMIS) produced in transfected Chinese hamster ovary cells has been highly purified by immunoaffinity chromatography. The introduction of a salt wash prior to elution of MIS from the affinity column

Taiwai Chin; Robert L. Parry; Patricia K. Donahoe

1991-01-01

175

Iron-chelating compounds produced by soil pseudomonads: correlation with fungal growth inhibition.  

PubMed

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. PMID:16346334

Vandenbergh, P A; Gonzalez, C F; Wright, A M; Kunka, B S

1983-07-01

176

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

NASA Technical Reports Server (NTRS)

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

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

1989-01-01

177

Butyrate inhibits the retinoic acid-induced differentiation of F9 teratocarcinoma stem cells.  

PubMed

F9 mouse teratocarcinoma stem cells differentiate into parietal endoderm cells in the presence of retinoic acid, dibutyryl cyclic AMP, and theophylline (RACT). When F9 cells are exposed to 2-5 mM sodium butyrate plus RACT, they fail to differentiate. Differentiation is assessed by induction of laminin and collagen IV mRNA, the synthesis of laminin, collagen IV and plasminogen activator proteins, and alterations in cell morphology. Butyrate inhibits differentiation only when added within 8 hr after retinoic acid addition. Thus an early event in retinoid action on F9 cells is butyrate-sensitive. The population doubling time and cell cycle distribution of F9 cells are not altered within the first 24 hr after butyrate addition, suggesting that butyrate does not inhibit differentiation by inhibition of growth or normal cycling. However, butyrate does inhibit histone deacetylation in F9 cells, and this could be the mechanism by which butyrate inhibits differentiation. PMID:6090244

Levine, R A; Campisi, J; Wang, S Y; Gudas, L J

1984-10-01

178

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

Microsoft Academic Search

High elastase and cathepsin G activities have been observed in chronic wounds. These levels can inhibit healing through degradation of growth factors, cytokines, and extracellular matrix proteins. Oleic acid (18:1) is a non-toxic elastase inhibitor with some potential for redressing the imbalance of elastase activity found in chronic wounds. Cotton wound dressing material was characterized as a transfer carrier for

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

2007-01-01

179

R-lipoic acid inhibits mammalian pyruvate dehydrogenase kinase.  

PubMed

The four pyruvate dehydrogenase kinase (PDK) and two pyruvate dehydrogenase phosphatase (PDP) isoenzymes that are present in mammalian tissues regulate activity of the pyruvate dehydrogenase complex (PDC) by phosphorylation/dephosphorylation of its pyruvate dehydrogenase (E1) component. The effect of lipoic acids on the activity of PDKs and PDPs was investigated in purified proteins system. R-lipoic acid, S-lipoic acid and R-dihydrolipoic acid did not significantly affect activities of PDPs and at the same time inhibited PDKs to different extents (PDK1>PDK4 approximately PDK2>PDK3 for R-LA). Since lipoic acids inhibited PDKs activity both when reconstituted in PDC and in the presence of E1 alone, dissociation of PDK from the lipoyl domains of dihydrolipoamide acetyltransferase in the presence of lipoic acids is not a likely explanation for inhibition. The activity of PDK1 towards phosphorylation sites 1, 2 and 3 of E1 was decreased to the same extent in the presence of R-lipoic acid, thus excluding protection of the E1 active site by lipoic acid from phosphorylation. R-lipoic acid inhibited autophosphorylation of PDK2 indicating that it exerted its effect on PDKs directly. Inhibition of PDK1 by R-lipoic acid was not altered by ADP but was decreased in the presence of pyruvate which itself inhibits PDKs. An inhibitory effect of lipoic acid on PDKs would result in less phosphorylation of E1 and hence increased PDC activity. This finding provides a possible mechanism for a glucose (and lactate) lowering effect of R-lipoic acid in diabetic subjects. PMID:15512796

Korotchkina, Lioubov G; Sidhu, Sukhdeep; Patel, Mulchand S

2004-10-01

180

Lovastatin inhibits pancreatic cancer growth regardless of RAS mutation.  

PubMed

Lovastatin, an inhibitor of the rate-limiting enzyme of cholesterol synthesis, inhibits growth of pancreatic cancer cells. A possible mechanism of this inhibition is that lovastatin inhibits the activity of RAS protein by depleting farnesyl (an intermediate of cholesterol synthesis). The K-ras gene is frequently mutated in pancreatic cancers and RAS protein requires farnesyl to be bound to the cell membrane and thereby activated. To investigate whether lovastatin inhibition of cell growth depends upon the presence of ras mutation, codons 12/13 and 61 of ras genes were examined by the dideoxynucleotide chain-terminating method in five pancreatic cell lines (human CAPAN2, CAV, MIA Paca2, PANCi, and hamster H2T) on which lovastatin exerted a growth-inhibitory effect. These codons play a major role in tumorigenic mutation of ras genes. Lovastatin inhibited cell growth by 99% (MIA), 97% (H2T), 78% (CAV), 41% (CAPAN2), and 23% (PANC1), respectively, when cells were treated with 2.5 micrograms/ml lovastatin for 6 days. Activating point mutations were found in codon 12 of the K-ras gene (wild type:GGT) in MIA (GTT), H2T (GAT), CAPAN2 (TGT), and PANC1 (GAT) but not in CAV. In addition, the CAV cell line did not have a mutation in either H- or N-ras genes. Lovastatin inhibited the growth of CAV cells even though this cell line did not have ras mutation, suggesting that lovastatin inhibition of pancreatic cancer cell growth is not directly dependent on the presence of ras mutation. PMID:7809022

Sumi, S; Beauchamp, R D; Townsend, C M; Pour, P M; Ishizuka, J; Thompson, J C

1994-09-01

181

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

Microsoft Academic Search

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

Jung-Chung Lin

2003-01-01

182

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

183

Effect of lactic acid bacteria on growth of Staphylococcus aureus.  

PubMed

Cultures of lactic acid bacteria, mostly from foods, were tested for their effect on the growth of Staphylococcus aureus in Trypticase Soy Broth (BBL). Some of the effectors, e.g., Streptococcus faecalis, S. faecium, Lactobacillus lactis, L. brevis, and Leuconostoc mesenteroides, stimulated growth of S. aureus during early hours of growth, especially at higher temperatures of incubation, but most cultures were inhibitory, and some (S. faecium and L. mesenteroides) were even killing by the time of attainment of the maximal phase of growth of the Staphylococcus. Low-temperature meat lactobacilli and Leuconostoc dextranicum inhibited S. aureus at 10, 15, 20, and 25 C throughout its growth. Streptococcus faecalis var. liquefaciens inhibited at these temperatures and at 30 and 37 C, as well. When the ratio of effectors to staphylococci in the inoculum was 100:1, the three enterococci, the meat Lactobacillus, and L. dextranicum prevented the attainment of 5 x 10(6) staphylococci per milliliter at 15 C, and all but the meat Lactobacillus did so at 22 C. A ratio of 1:1 accomplished similar results at 15 C, except that S. aureus was only delayed for 12 hr by S. faecalis. A ratio of 1:100 usually was ineffective. In general, the more effector bacteria there were in the inoculum, the greater was the overall inhibition (or stimulation) of S. aureus. Inhibition was most effective at 10 or 15 C, less so at 20 or 25 C, and least at 30 or 37 C, whereas stimulation during early growth was greater at the higher temperatures. Results with different strains of the effectors and with two strains of S. aureus were similar, for the most part. PMID:4959983

Kao, C T; Frazier, W C

1966-03-01

184

d-Amino Acids Indirectly Inhibit Biofilm Formation in Bacillus subtilis by Interfering with Protein Synthesis  

PubMed Central

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

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

2013-01-01

185

Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status.  

PubMed

Potential antiproliferative effects of tocotrienols, the major vitamin E component in palm oil, were investigated on the growth of both estrogen-responsive (ER+) MCF7 human breast cancer cells and estrogen-unresponsive (ER-) MDA-MB-231 human breast cancer cells, and effects were compared with those of alpha-tocopherol (alphaT). The tocotrienol-rich fraction (TRF) of palm oil inhibited growth of MCF7 cells in both the presence and absence of estradiol with a nonlinear dose-response but such that complete suppression of growth was achieved at 8 microg/mL. MDA-MB-231 cells were also inhibited by TRF but with a linear dose-response such that 20 microg/mL TRF was needed for complete growth suppression. Separation of the TRF into individual tocotrienols revealed that all fractions could inhibit growth of both ER+ and ER- cells and of ER+ cells in both the presence and absence of estradiol. However, the gamma- and delta-fractions were the most inhibitory. Complete inhibition of MCF7 cell growth was achieved at 6 microg/mL of gamma-tocotrienol/delta-tocotrienol (gammaT3/deltaT3) in the absence of estradiol and 10 microg/mL of deltaT3 in the presence of estradiol, whereas complete suppression of MDA-MB-231 cell growth was not achieved even at concentrations of 10 microg/mL of deltaT3. By contrast to these inhibitory effects of tocotrienols, alphaT had no inhibitory effect on MCF7 cell growth in either the presence or the absence of estradiol, nor on MDA-MB-231 cell growth. These results confirm studies using other sublines of human breast cancer cells and demonstrate that tocotrienols can exert direct inhibitory effects on the growth of breast cancer cells. In searching for the mechanism of inhibition, studies of the effects of TRF on estrogen-regulated pS2 gene expression in MCF7 cells showed that tocotrienols do not act via an estrogen receptor-mediated pathway and must therefore act differently from estrogen antagonists. Furthermore, tocotrienols did not increase levels of growth-inhibitory insulin-like growth factor binding proteins (IGFBP) in MCF7 cells, implying also a different mechanism from that proposed for retinoic acid inhibition of estrogen-responsive breast cancer cell growth. Inhibition of the growth of breast cancer cells by tocotrienols could have important clinical implications not only because tocotrienols are able to inhibit the growth of both ER+ and ER- phenotypes but also because ER+ cells could be growth-inhibited in the presence as well as in the absence of estradiol. Future clinical applications of TRF could come from potential growth suppression of ER+ breast cancer cells otherwise resistant to growth inhibition by antiestrogens and retinoic acid. PMID:9625593

Nesaretnam, K; Stephen, R; Dils, R; Darbre, P

1998-05-01

186

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

187

Bacterial ammonia causes significant plant growth inhibition.  

PubMed

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. PMID:23691060

Weise, Teresa; Kai, Marco; Piechulla, Birgit

2013-01-01

188

Pharmacological Inhibition of BMK1 Suppresses Tumor Growth Through PML  

PubMed Central

SUMMARY BMK1 is activated by mitogens and oncogenic signals and, thus, is strongly implicated in tumorigenesis. We found that BMK1 interacted with promyelocytic leukemia protein (PML), and inhibited its tumor-suppressor function through phosphorylation. Furthermore, activated BMK1 notably inhibited PML-dependent activation of p21. To further investigate the BMK-mediated inhibition of the tumor suppressor activity of PML in tumor cells, we developed a small-molecule inhibitor of the kinase activity of BMK1, XMD8-92. Inhibition of BMK1 by XMD8-92 blocked tumor cell proliferation in vitro and significantly inhibited tumor growth in vivo by 95%, demonstrating the efficacy and tolerability of BMK1-targeted cancer treatment in animals.

Yang, Qingkai; Deng, Xianming; Lu, Bingwen; Cameron, Michael; Fearns, Colleen; Patricelli, Matthew P.

2010-01-01

189

Inhibition of cortical collecting tubule chloride transport by organic acids.  

PubMed Central

Cl self-exchange by the rabbit cortical collecting tubule (CCT) occurs via an apical anion exchanger in series with a basolateral Cl conductance. We studied the effects of organic acids on CCT Cl self-exchange. We found no evidence for transport of acid anions by the self-exchange system. Rather, Cl self-exchange was inhibited by a variety of organic acids. The degree of inhibition correlated with the chloroform/water partition coefficient and was enhanced by lowering pH, indicating inhibition by the lipid-soluble, protonated species. Inhibition by the representative acid iso-butyrate was dose-dependent and showed sidedness (basolateral greater than apical). Iso-butyrate also reversibly reduced transepithelial conductance without altering K permeability, suggesting inhibition of the principal cell basolateral Cl conductance. Because small organic compounds with similar lipid solubilities but no carboxyl group had no effect, both the carboxyl group and the lipid-solubility of organic acids appear to be important. The results are consistent with blockade of chloride channels by organic acids.

Matsuzaki, K; Stokes, J B; Schuster, V L

1988-01-01

190

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

191

Inhibition of plant fatty acid synthesis by nitroimidazoles.  

PubMed Central

1. The effect of the addition of a number of nitroimidazoles was tested on fatty acid synthesis by germinating pea seeds, isolated lettuce chloroplasts and a soluble fraction from pea seeds. 2. All the compounds tested had a marked inhibition on stearate desaturation by lettuce chloroplasts and on the synthesis of very-long-chain fatty acids by pea seeds. 3. In contrast, the effect of the drugs on total fatty acid synthesis from [14C]acetate in chloroplasts was related to the compound's electron reduction potentials. 4. Of the compounds used, only metronidazole had a marked inhibition on palmitate elongation in the systems tested. 5. The mechanism of inhibition of plant fatty acid synthesis by nitroimidazoles is discussed and the possible relevance of these findings to their neurotoxicity is suggested.

Jones, A V; Harwood, J L; Stratford, M R; Stumpf, P K

1981-01-01

192

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

SciTech Connect

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

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

2012-11-16

193

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

PubMed

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

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

2010-03-31

194

Rosmarinic acid inhibits lung injury induced by diesel exhaust particles.  

PubMed

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) may be involved in recent increases in lung diseases. DEP has been shown to generate reactive oxygen species. Intratracheal instillation of DEP induces lung inflammation and edema in mice. Rosmarinic acid is a naturally occurring polyphenol with antioxidative and anti-inflammatory activities. We investigated the effects of rosmarinic acid on lung injury induced by intratracheal administration of DEP (500 microg/body) in mice. Oral supplementation with administration of rosmarinic acid (2 mg/body for 3 d) inhibited DEP-induced lung injury, which was characterized by neutrophil sequestration and interstitial edema. DEP enhanced the lung expression of keratinocyte chemoattractant (KC), interleukin-1beta, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha, which was inhibited by treatment with rosmarinic acid. DEP enhanced expression of iNOS mRNA and formation of nitrotyrosine and 8-OHdG in the lung, which was also inhibited by rosmarinic acid. These results suggest that rosmarinic acid inhibits DEP-induced lung injury by the reduction of proinflammatory molecule expression. Antioxidative activities of rosmarinic acid may also contribute to its protective effects. PMID:12684091

Sanbongi, Chiaki; Takano, Hirohisa; Osakabe, Naomi; Sasa, Naoko; Natsume, Midori; Yanagisawa, Rie; Inoue, Ken-ichiro; Kato, Yoji; Osawa, Toshihiko; Yoshikawa, Toshikazu

2003-04-15

195

Use of massoialactone for inhibition of fungal growth  

US Patent & Trademark Office Database

Massoialactone is useful for preventing or at least inhibiting growth of a fungus. Accordingly, a fungicidal composition has massoialactone as an active antifungal compound together with an agronomically acceptable carrier therefor. Additional antifungal ingredients can be added to the composition. The composition can be applied to surfaces, including surfaces of plants and plant parts, such as seeds.

2000-05-09

196

Cyclosporin A blocks bile acid synthesis in cultured hepatocytes by specific inhibition of chenodeoxycholic acid synthesis.  

PubMed Central

Bile acid synthesis, determined by conversion of [4-14C]cholesterol into bile acids in rat and human hepatocytes and by measurement of mass production of bile acids in rat hepatocytes, was dose-dependently decreased by cyclosporin A, with 52% (rat) and 45% (human) inhibition of 10 microM. The decreased bile acid production in rat hepatocytes was due only to a fall in the synthesis of beta-muricholic and chenodeoxycholic acids (-64% at 10 microM-cyclosporin A), with no change in the formation of cholic acid. In isolated rat liver mitochondria, 26-hydroxylation of cholesterol was potently inhibited by the drug (concn. giving half-maximal inhibition = 4 microM). These results suggest that cyclosporin A blocks the alternative pathway in bile acid synthesis, which leads preferentially to the formation of chenodeoxycholic acid.

Princen, H M; Meijer, P; Wolthers, B G; Vonk, R J; Kuipers, F

1991-01-01

197

Hydrophobic poly (amino acid)-modified PEI-mediated delivery of single-chain antibody scFv1C9 inhibits HepG2 cell cycle process and xenograft growth in nude mice.  

PubMed

The safe and effective gene delivery vector remains the key step for gene therapy. Hydrophobic-modified Phe-PEI (PP80) was exhibited in advantage with biocompatibility and gene delivery with smaller size and easier penetration into cells and tissues. PP80 delivery of rev-casp-3 gene was demonstrated effectively to inhibit HeLa xenograft growth in our previous work. However, it was necessary to evaluate its applicability in other cells or tissues as gene carrier. Here, we quantitatively optimized the complex ratio of PP80 and plasmid DNA (pDNA) and evaluated the potential pyrogenicity by rabbit pyrogen test. In addition, PP80-mediated expression of scFv1C9 gene blocked HepG2 cell cycle progress in vitro. Subsequently, PP80-scFv1C9 was injected into HepG2 xenograft and significantly inhibited the xenograft growth in nude mice. Further investigation indicated that PP80 was an effective gene carrier and possible for entering hepatic xenograft. These features of PP80 made it attractive as a potential gene carrier for cancer therapy. PMID:24754301

Fu, Chunling; Zheng, Daxue; Shi, Hengliang; Tian, Huayu; Zhu, Xiaojuan; Chen, Xuesi

2014-06-01

198

Inhibition of ATP citrate lyase induces triglyceride accumulation with altered fatty acid composition in cancer cells.  

PubMed

De novo lipogenesis is activated in most cancers and several lipogenic enzymes have been implicated as therapeutic targets. Here, we demonstrate a novel function of the lipogenic enzyme, ATP citrate lyase (ACLY), in lipid metabolism in cancer cells. ACLY depletion by small interfering RNAs caused growth suppression and/or apoptosis in a subset of cancer cell lines. To investigate the effect of ACLY inhibition on lipid metabolism, metabolome and transcriptome analysis was performed. ACLY depletion blocks the fatty acid chain elongation from C16 to C18 in triglyceride (TG), but not in other lipid classes. Meanwhile, wild-type ACLY overexpression enhanced fatty acid elongation of TG, whereas an inactive mutant ACLY did not change it. ACLY depletion-mediated blockade of fatty acid elongation was coincident with downregulation of long-chain fatty acid elongase ELOVL6, which resides in endoplasmic reticulum (ER). Paradoxically, ACLY depletion-mediated growth suppression was associated with TG accumulation. ACLY depletion downregulated the expression of carnitine palmitoyltransferase 1A, which is a mitochondrial fatty acid transporter. Consistent with this finding, metabolome analysis revealed that ACLY positively regulates the carnitine system, which plays as an essential cofactor for fatty acid transport across mitochondrial membrane. AICAR, an activator of mitochondrial fatty acid oxidation (FAO), significantly reduced ACLY depletion-mediated TG accumulation. These data indicate that inhibition of ACLY might affect both fatty acid elongation in ER and FAO in mitochondria, thereby explaining the TG accumulation with altered fatty acid composition. This phenotype may be a hallmark of growth suppression mediated by ACLY inhibition. PMID:24310723

Migita, Toshiro; Okabe, Sachiko; Ikeda, Kazutaka; Igarashi, Saori; Sugawara, Shoko; Tomida, Akihiro; Soga, Tomoyoshi; Taguchi, Ryo; Seimiya, Hiroyuki

2014-07-01

199

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

PubMed

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

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

2010-06-01

200

Green tea catechins inhibit vascular endothelial growth factor receptor phosphorylation.  

PubMed

Vascular endothelial growth factor (VEGF) receptors (VEGFR) play a major role in tumor angiogenesis and, thus, represent attractive targets for the development of novel anticancer therapeutics. In this work, we report that green tea catechins are novel inhibitors of VEGFR-2 activity. Physiological concentrations (0.01-1 microM) of epigallocatechin-3 gallate, catechin-3 gallate, and, to a lesser extent, epicatechin-3 gallate induce a rapid and potent inhibition of VEGF-dependent tyrosine phosphorylation of VEGFR-2. The inhibition of VEGFR-2 by epigallocatechin-3 gallate was similar to that induced by Semaxanib (SU5416), a specific VEGFR-2 inhibitor. The inhibition of VEGFR-2 activity by the catechins displayed positive correlation with the suppression of in vitro angiogenesis. These observations suggest that the anticancer properties of green tea extracts may be related to their inhibition of VEGF-dependent angiogenesis. PMID:11809684

Lamy, Sylvie; Gingras, Denis; Béliveau, Richard

2002-01-15

201

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

PubMed

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

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

2013-05-28

202

Effects of acidity on tree pollen germination and tube growth  

SciTech Connect

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

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

1985-01-01

203

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

204

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

Microsoft Academic Search

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

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

2003-01-01

205

Kaurenoic Acid from Aralia continentalis Inhibits Biofilm Formation of Streptococcus mutans  

PubMed Central

We isolated a single chemical compound from A. continentalis and identified it to be kaurenoic acid (KA) and investigated the influence of anticariogenic properties. Inhibitory effects of KA on cariogenic properties such as growth, acid production, biofilm formation, and the adherence of S. mutans were evaluated. Furthermore, real-time PCR analysis was performed to evaluate the influence of KA on the genetic expression of virulence factors. KA significantly inhibited the growth and acid production of S. mutans at 2–4??g/mL and 4??g/mL of KA, respectively. Furthermore, the adherence onto S-HAs was inhibited at 3-4??g/mL of KA and biofilm formation was significantly inhibited when treated with 3??g/mL KA and completely inhibited at 4??g/mL. Also, the inhibitory effect of KA on biofilm formation was confirmed by SEM. In confocal laser scanning microscopy, bacterial viability gradually decreased by KA in a dose dependent manner. Real-time PCR analysis showed that the expressions of gtfB, gtfC, gbpB, spaP, brpA, relA, and vicR were significantly decreased in S. mutans when it was treated with KA. These results suggest that KA from A. continentalis may be a useful agent for inhibiting the cariogenic properties of S. mutans.

Jeong, Seung-Il; Kim, Beom-Su; Keum, Ki-Suk; Lee, Kwang-Hee; Kang, Sun-Young; Park, Bok-Im; Lee, Young-Rae; You, Yong-Ouk

2013-01-01

206

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

2013-10-16

207

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

208

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

PubMed Central

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

2013-01-01

209

Eicosapentaenoic acid inhibits endothelial cell migration in vitro  

PubMed Central

Background As n-3 Polyunsaturated Fatty Acids exert a beneficial action on the cardiovascular system, it is important to investigate their effects on endothelial cell responses that (like migration) contribute to repairing vascular lesions. Methods To this purpose, using functional and morphological in vitro assays, we have examined the effect of n-3 Polyunsaturated Fatty Acids on the migration of endothelial cells. Results We report here that incubation of endothelial cells with n-3 Polyunsaturated Fatty Acids impaired cell migration into a wound, triggered peripheral distribution of focal adhesions and caused partial disassembly of actin filaments. We also found that eicosapentaenoic acid and docosahexaenoic acid exerted similar effects on the focal adhesions, but that eicosapentaenoic acid was sufficient for inhibiting cell migration. Conclusions Given the importance of endothelial cell migration in the repair of vascular injuries, these in vitro findings call for in vivo evaluation of vascular repair in response to different dietary ratios of eicosapentaenoic to docosahexaenoic acid.

2010-01-01

210

Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines.  

PubMed

Although accumulating evidence suggests a chemopreventive role for folic acid in colon cancer, the regulation of this process in unknown. We hypothesize that supplemental folic acid exerts its chemopreventive role by inhibiting mucosal hyperproliferation, an event considered to be central to the initiation of carcinogenesis in the gastrointestinal tract. The present investigation examines the effect of supplemental folic acid on proliferation of Caco-2 and HCT-116 colon cancer cell lines. Furthermore, because certain tyrosine kinases, particularly epidermal growth factor receptor (EGFR), play a role in regulating cell proliferation, we also examined the folic acid-induced changes in tyrosine kinase activity and expression of EGFR. In Caco-2 and HCT-116 cells, maintained in RPMI 1640 medium containing 1 microg/ml folic acid, we observed that the supplemental folic acid inhibited proliferation in a dose-dependent manner. Pretreatment of HCT-116 and Caco-2 cell lines with supplemental folic acid (1.25 microg/ml) completely abrogated transforming growth factor-alpha (TGF-alpha)-induced proliferation in both cell lines. Tyrosine kinase activity and the relative concentration of EGFR were markedly diminished in both cell lines following a 24-h exposure to supplemental folic acid. The folic acid-induced inhibition of EGFR tyrosine kinase activity in colon cancer cell lines was also associated with a concomitant reduction in the relative concentration of the 14-kDa membrane-bound precursor form of TGF-alpha. In conclusion, our data suggest that supplemental folic acid is effective in reducing proliferation in two unrelated colon cancer cell lines and that EGFR tyrosine kinase appears to be involved in regulating this process. PMID:10600765

Jaszewski, R; Khan, A; Sarkar, F H; Kucuk, O; Tobi, M; Zagnoon, A; Dhar, R; Kinzie, J; Majumdar, A P

1999-12-01

211

Mullerian Inhibiting Substance (MIS) Augments IFN-gamma Mediated Inhibition of Breast Cancer Cell Growth.  

National Technical Information Service (NTIS)

Mullerian Inhibiting Substance (MIS), a member of the TGFB family regulates growth, differentiation, and apoptosis in many cell types In the male embryo, MIS causes regression of the Mullerian duct. However, the presence of MIS type II receptor gene in th...

V. Gupta S. Maheswaran

2004-01-01

212

Mullerian Inhibiting Substances (MIS) Augments IFN-gamma Mediated Inhibition of Breast Cancer Cell Growth.  

National Technical Information Service (NTIS)

MIS is a member of the TGF family. The purpose of this study is to test the hypothesis that MIS and IFN-gamma might be more effective in the inhibition of breast cancer cell growth than either agent alone. We observed MIS and IFN-gamma costimulate IRF1 ex...

V. Gupta

2006-01-01

213

Inhibition of yeast ribonucleic acid polymerases by thiolutin.  

PubMed

Yeast ribonucleic acid (RNA) polymerase II, isolated after fractionation on diethylaminoethyl (DEAE)-cellulose (DE-52) or on DEAE-Sephadex (A-25), is 50% inhibited by 1.5 mug of alpha-amanitin. This inhibition is independent of the sequence of interaction of enzyme, template, nucleotides, and antibiotic and is expressed immediately on addition of alpha-amanitin to a preparation actively synthesizing RNA. Thus, alpha-amanitin's primary effect is inhibition of elongation of preinitiated RNA sequences in this system, as in others. A single peak of alpha-amanitin-resistant RNA polymerase activity (I) was eluted before enzyme II on either column. On A-25 but not on DE-52, a third peak of activity (III) was eluted after enzyme II. This activity was also resistant to alpha-amanitin. Enzymes I, II, and III were 50% inhibited by 3, 4, and 3 mug of thiolutin per ml, respectively. The extent of inhibition was independent of the nature of the template (native or denatured salmon sperm deoxyribonucleic acid or poly(dA-dT) or of the presence of 0.4 mM dithiothreitol, but this marked inhibition was only seen when enzymes were preincubated with thiolutin in the absence of template. Template protected the enzymes against thiolutin in the absence of nucleotides. Either the sensitive site on the polymerase is only accessible to thiolutin before interaction with template or thiolutin inhibits functional polymerase-template interaction but not elongation of preinitiated RNA chains. PMID:4583213

Tipper, D J

1973-10-01

214

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

2012-06-01

215

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

216

Epidermal Growth Factor Receptor-Related Protein Inhibits Cell Growth and Invasion in Pancreatic Cancer  

Microsoft Academic Search

The epidermal growth factor receptor (EGFR) signaling network plays critical roles in human cancers, including pancreatic cancer, suggesting that the discovery of specific agents targeting EGFR would be extremely valuable for pancreatic cancer therapy.EGFR-related protein (ERRP), a recently identified pan-erbB inhibitor, has been shown to inhibit growth and induce apoptosis of pancreatic cancer cells in vitro and tumor growth in

Zhiwei Wang; Radha Sengupta; Sanjeev Banerjee; Yiwei Li; Yuxiang Zhang; Ramzi Mohammad; James L. Abbruzzese; Fazlul H. Sarkar

2006-01-01

217

Inhibition of acid-catalyzed depolymerization of cellulose with boric acid in non-aqueous acidic media.  

PubMed

Boric acid inhibited the acid-catalyzed depolymerization of cellulose in sulfolane, a non-aqueous medium, at high temperature. Formation of the dehydration products such as levoglucosenone, furfural, and 5-hydroxymethyl furfural were also effectively inhibited. Similar inhibition was observed for cellooligosaccharides and starch, although the glucosidic bonds in methyl glucopyranosides and methyl cellobioside were cleaved to form alpha-d-glucofuranose cyclic 1,2:3,5-bisborate. PMID:18045577

Kawamoto, Haruo; Saito, Shinya; Saka, Shiro

2008-02-01

218

Gastric acid inhibition in the treatment of peptic ulcer hemorrhage  

Microsoft Academic Search

Upper gastrointestinal bleeding from peptic ulcer disease is a common clinical event, resulting in considerable patient morbidity\\u000a and significant health care costs. Inhibiting gastric acid secretion is a key component in improving clinical outcomes, including\\u000a reducing rebleeding, transfusion requirements, and surgery. Raising intragastric pH promotes clot stability and reduces the\\u000a influences of gastric acid and pepsin. Patients with high-risk stigmata

Kevin A. Ghassemi; Thomas O. G. Kovacs; Dennis M. Jensen

2009-01-01

219

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

220

[The mechanisms of the inhibition of gastric acid secretion induced by intraduodenal amino acids in rats].  

PubMed

We investigated the effect of intraduodenal amino acids (AA) on gastric acid secretion and gastrin release, and possible role of endogenous secretin on this phenomenon in vivo in rats. Intraduodenal administration of mixed AA solution (140 mg/hr, pH6.5) resulted in significant inhibition of gastric acid secretion and gastrin release stimulated by intragastric perfusion of peptone (0.5%). Intravenous infusion of secretin (0.05CU/kg/hr) also inhibited peptone-stimulated gastric acid secretion and gastrin release. Furthermore, the AA-induced suppression of gastric acid secretion was significantly blocked by intravenous injection of rabbit anti-secretin serum. In conclusion, intraduodenal AA inhibit peptone-stimulated gastric acid secretion and gastrin release, and endogenous secretin released by AA is attributed to this suppression. Thus, the result of this study indicates that intestinal AA regulate gastric secretory function mediated by AA-released endogenous secretin in the intestinal phase. PMID:9028138

Ikeda, M; Shiratori, K; Shimizu, K; Watanabe, S; Hayashi, N

1997-01-01

221

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

222

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

2012-04-16

223

Inhibition of endothelial cell proliferation and angiogenesis by orlistat, a fatty acid synthase inhibitor.  

PubMed

Orlistat, an antiobesity drug, is cytostatic and cytotoxic to tumor cells. The antitumor activity of orlistat can be attributed to its ability to inhibit the thioesterase domain of fatty acid synthase (FAS). The objective of the present study was to test the effect of orlistat on endothelial cell proliferation and angiogenesis. Orlistat inhibits endothelial cell FAS, blocks the synthesis of fatty acids, and prevents endothelial cell proliferation. More significantly, orlistat inhibits human neovascularization in an ex vivo assay, which suggests that it may be useful as an antiangiogenic drug. The mechanism of these effects can be traced to the fact that orlistat prevents the display of the vascular endothelial growth factor (VEGF) receptor (VEGFR2/KDR/Flk1) on the endothelial cell surface. Thus, orlistat is an antiangiogenic agent with a novel mechanism of action. PMID:17012255

Browne, Cecille D; Hindmarsh, Elizabeth J; Smith, Jeffrey W

2006-10-01

224

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

225

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

PubMed Central

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

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

2011-01-01

226

Miniaturized kinetic growth inhibition assay with denitrifying bacteria Paracoccus denitrificans.  

PubMed

A method to cultivate anaerobic bacteria on standard 96-well microplates with automatic recording of growth curves is presented. The method was used as a kinetic growth inhibition assay with denitrifying bacteria Paracoccus denitrificans, and applied to various heavy metal ions and selected agrochemicals. Incorporated in a battery of other biotest the assay could take into account effects of toxicants on denitrifying organisms. The results (EC50) revealed that the assay was relatively sensitive. Performed in vials, the assay was also applied to toxicity testing of volatile compounds and represented a convenient method for assessing samples containing volatile constituents. PMID:15910901

Koutny, Marek; Zaoralkova, Linda

2005-06-01

227

Systemic Par-4 inhibits non-autochthonous tumor growth.  

PubMed

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

Zhao, Yanming; Burikhanov, Ravshan; Brandon, Jason; Qiu, Shirley; Shelton, Brent J; Spear, Brett; Bondada, Subbarao; Bryson, Scott; Rangnekar, Vivek M

2011-07-15

228

Growth inhibition of Mycobacterium smegmatis by mycobacteriophage-derived enzymes.  

PubMed

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

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

2014-09-01

229

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

PubMed Central

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

2014-01-01

230

Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses  

Microsoft Academic Search

Bacterial infection often results in the formation of tissue abscesses, which represent the primary site of interaction between invading bacteria and the innate immune system. We identify the host protein calprotectin as a neutrophil-dependent factor expressed inside Staphylococcus aureus abscesses. Neutrophil-derived calprotectin inhibited S. aureus growth through chelation of nutrient Mn2+ and Zn2+: an activity that results in reprogramming of

Brian D. Corbin; Erin H. Seeley; Andrea Raab; Joerg Feldmann; Michael R. Miller; Victor J. Torres; Kelsi L. Anderson; Brian M. Dattilo; Paul M. Dunman; Russell Gerads; Richard M. Caprioli; Wolfgang Nacken; Walter J. Chazin; Eric P. Skaar

2008-01-01

231

Elevated serum free fatty acid concentrations inhibit T lymphocyte signaling  

Microsoft Academic Search

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

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

232

Inhibition Enzyme Sensor for Nicotine, Nicotinamide and Nicotinic Acid Determination  

NASA Astrophysics Data System (ADS)

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

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

2000-12-01

233

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

234

Inhibition of Mycobacterial Alanine Racemase Activity and Growth by Thiadiazolidinones  

PubMed Central

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 µM and 23 to >150 µM, 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 µg/ml to 100 µg/ml, and from 1.56 to 6.25 µg/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.

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.

2013-01-01

235

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

Microsoft Academic Search

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

A. Santi; T. June

236

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

2013-03-01

237

Vasostatin, a Calreticulin Fragment, Inhibits Angiogenesis and Suppresses Tumor Growth  

Microsoft Academic Search

Summary An endothelial cell inhibitor was purified from supernatant of an Epstein-Barr virus-immortal- ized cell line and identified as fragments of calreticulin. The purified recombinant NH 2 -termi- nal domain of calreticulin (amino acids 1-180) inhibited the proliferation of endothelial cells, but not cells of other lineages, and suppressed angiogenesis in vivo. We have named this NH 2 - terminal

Sandra E. Pike; Lei Yao; Karen D. Jones; Barry Cherney; Ettore Appella; Kazuyasu Sakaguchi; Hira Nakhasi; Julie Teruya-Feldstein; Peter Wirth; Ghanshyam Gupta; Giovanna Tosato

2010-01-01

238

Nur77 inhibits androgen-induced bladder cancer growth.  

PubMed

Currently, bladder cancer ranks as the second most common genitourinary malignancy which is exacting significant morbidity and mortality worldwide. Although there are abundant epidemiological and basic studies which strongly suggest the role of androgen hormone in bladder cancer, the underlying mechanism is not fully understood. In the current study, we sought to identify a new competitive inhibitor for androgen receptor in bladder cancer cells. Our results showed that Nur77 hyperexpression inhibits UM-UC-3 cell growth and cell cycle progression while Nur77 knockdown exerts the opposite effect. In our cell culture model, we also demonstrated that Nur77 competitively inhibits androgen-dependent transcription activity and more specifically, Nur77 competes with androgen receptor for binding to src-1, a well-known coactivator for steroids. More importantly, we also showed that a small molecule agonist for Nur77, Cytosporone B, significantly inhibits androgen-dependent bladder cancer cell growth in two different cell lines. These data provide a good proof-of-principle that Nur77 signaling machinery could be a new target for growth control of androgen-dependent bladder cancer cells. PMID:24299210

Wu, Jianping; Liu, Jun; Jia, Ruipeng; Song, Hongbin

2013-12-01

239

Studies of the effect of gibberellic acid on algal growth.  

NASA Technical Reports Server (NTRS)

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

Evans, W. K.; Sorokin, C.

1971-01-01

240

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

241

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

242

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

2012-10-01

243

Growth of Leptospira Canicola in the Presence of Fatty Acids.  

National Technical Information Service (NTIS)

It was not possible to grow Leptospira canicola beyond the third passage unless the medium contained gelatin. In the presence of gelatin, only enanthic acid and valerianic acid among the short-chained fatty acids showed distinct growth promotion. Continua...

H. Woratz

1968-01-01

244

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

245

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

PubMed Central

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

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

2012-01-01

246

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

247

Growth Inhibition After Exposure to Transforming Growth Factor-?1 in Human Bladder Cancer Cell Lines  

PubMed Central

Purpose Transforming growth factor-?1 (TGF-?1) plays a dual role in apoptosis and in proapoptotic responses in the support of survival in a variety of cells. The aim of this study was to determine the function of TGF-?1 in bladder cancer cells. Materials and Methods The role of TGF-?1 in bladder cancer cells was examined by observing cell viability by using the tetrazolium dye (MTT) assay after treating the bladder cancer cell lines 253J, 5637, T24, J82, HT1197, and HT1376 with TGF-?1. Among these cell lines, the 253J and T24 cell lines were coincubated with TGF-?1 and the pan anti-TGF-? antibody. Fluorescence-activated cell sorter (FACS) analysis was performed to determine the mechanism involved after TGF-?1 treatment in 253J cells. Results All six cell lines showed inhibited cellular growth after TGF-?1 treatment. Although the T24 and J82 cell lines also showed inhibited cellular growth, the growth inhibition was less than that observed in the other 4 cell lines. The addition of pan anti-TGF-? antibodies to the culture media restored the growth properties that had been inhibited by TGF-?1. FACS analysis was performed in the 253J cells and the 253J cells with TGF-?1. There were no significant differences in the cell cycle between the two treatments. However, there were more apoptotic cells in the TGF-?1-treated 253J cells. Conclusions TGF-?1 did not stimulate cellular proliferation but was a growth inhibitory factor in bladder cancer cells. However, the pattern of its effects depended on the cell line. TGF-?1 achieved growth inhibition by enhancing the level of apoptosis.

Lee, Changho; Lee, Sang-Han; Kim, Doo Sang; Jeon, Yun Soo; Lee, Nam Kyu

2014-01-01

248

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

249

RARalpha is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells.  

PubMed

Retinoids are used for treatment of acute promyelocytic leukemia (APL). Am-80, Tamibarotene, binds to retinoic acid receptor alpha (RARalpha) more specifically than all-trans retinoic acid. We studied the tumor cell suppressive effects of Am-80, with respect to cytotoxicity and growth inhibition using eight myeloid and lymphoid malignant cells in culture (HL-60, HL-60R, K-562, Kasumi-1, MEG01, Raji, U266B1, and U937). The effects of Am-80 were examined during 9 days of incubation with 10(-7)-10(-5) M of Am-80 in culture medium, which was changed every 3 days. HL-60 were the only cells sensitive to Am-80-induced cytotoxicity; the latter reached more than 95% after 9 days of incubation, and death was primarily through apoptosis. The total mass of RARalpha in HL-60 was significantly greater (p<0.006) than in ATRA-resistant HL-60 (HL-60R) as well as all of other cells tested. However, in all cells excluding HL-60, Am-80 induced time- and dose-dependent cell growth inhibition without noticeable cytotoxicity. TGF-beta2 was released into the media containing cells incubated with Am-80 for 3 days. A dose-dependent increment of phosphorylation of Smad-2 was also detected. The relative amount of secreted TGF-beta2 correlated with the growth inhibition rates in all cells tested excluding HL-60, and with the total mass of RARalpha in the cells (p=0.0137). Our results indicate that Am-80-induced cell-type non-specific growth inhibition is mediated by TGF-beta2, where the total mass of RARalpha could be an important regulatory factor in hematologic malignant cells. PMID:17611697

Jimi, Shiro; Mashima, Kota; Matsumoto, Taichi; Hara, Shuji; Suzumiya, Junji; Tamura, Kazuo

2007-08-01

250

Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors.  

PubMed

Specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 are highly expressed in rhabdomyosarcoma (RMS) cells. In tissue arrays of RMS tumor cores from 71 patients, 80% of RMS patients expressed high levels of Sp1 protein, whereas low expression of Sp1 was detected in normal muscle tissue. The non-steroidal anti-inflammatory drug (NSAID) tolfenamic acid (TA) inhibited growth and migration of RD and RH30 RMS cell lines and also inhibited tumor growth in vivo using a mouse xenograft (RH30 cells) model. The effects of TA were accompanied by downregulation of Sp1, Sp3, Sp4 and Sp-regulated genes in RMS cells and tumors, and the role of Sp protein downregulation in mediating inhibition of RD and RH30 cell growth and migration was confirmed by individual and combined knockdown of Sp1, Sp3 and Sp4 proteins by RNA interference. TA treatment and Sp knockdown in RD and RH30 cells also showed that four genes that are emerging as individual drug targets for treating RMS, namely c-MET, insulin-like growth factor receptor (IGFR), PDGFR? and CXCR4, are also Sp-regulated genes. These results suggest that NSAIDs such as TA may have potential clinical efficacy in drug combinations for treating RMS patients. PMID:22815231

Chadalapaka, Gayathri; Jutooru, Indira; Sreevalsan, Sandeep; Pathi, Satya; Kim, Kyounghyun; Chen, Candy; Crose, Lisa; Linardic, Corinne; Safe, Stephen

2013-02-15

251

INHIBITION OF RHABDOMYOSARCOMA CELL AND TUMOR GROWTH BY TARGETING SPECIFICITY PROTEIN (Sp) TRANSCRIPTION FACTORS  

PubMed Central

Specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 are highly expressed in rhabdomyosarcoma (RMS) cells. In tissue arrays of RMS tumor cores from 71 patients, 80% of RMS patients expressed high levels of Sp1 protein, whereas low expression of Sp1 was detected in normal muscle tissue. The non-steroidal anti-inflammatory drug (NSAID) tolfenamic acid (TA) inhibited growth and migration of RD and RH30 RMS cell lines and also inhibited tumor growth in vivo using a mouse xenograft (RH30 cells) model. The effects of TA were accompanied by downregulation of Sp1, Sp3, Sp4 and Sp-regulated genes in RMS cells and tumors, and the role of Sp protein downregulation in mediating inhibition of RD and RH30 cell growth and migration was confirmed by individual and combined knockdown of Sp1, Sp3 and Sp4 proteins by RNA interference. TA treatment and Sp knockdown in RD and RH30 cells also showed that four genes that are emerging as individual drug targets for treating RMS, namely c-MET, insulin-like growth factor receptor (IGFR), PDGFR? and CXCR4, are also Sp-regulated genes. These results suggest that NSAIDs such as TA may have potential clinical efficacy in drug combinations for treating RMS patients.

Chadalapaka, Gayathri; Jutooru, Indira; Sreevalsan, Sandeep; Pathi, Satya; Kim, Kyounghyun; Chen, Candy; Crose, Lisa; Linardic, Corinne; Safe, Stephen

2012-01-01

252

Sodium Valproate Inhibits the Growth of Human Cholangiocarcinoma In Vitro and In Vivo  

PubMed Central

Background. None of treatment options for Cholangiocarcinoma (CCA), including surgery, adjuvant radiotherapy and chemotherapy, and ultimately liver transplantation, have been shown to substantially improve the survival rate in patients with CCA. Valproic acid (VPA), a histone deacetylase inhibitor, has been shown to display potent antitumor effects. In this study, sodium valproate, the clinically available form of VPA, was tested for its ability to inhibit the growth of cholangiocarcinoma cells, both in vitro and in vivo. Materials and Methods. Cholangiocarcinoma cells (TFK-1, QBC939, and CCLP1) of different origins were treated with sodium valproate to determine their effects on cell proliferation and differentiation, cell cycle regulation, apoptosis, and autophagy. The in vivo effects of sodium valproate on cholangiocarcinoma growth were assessed using a xenograft mouse model injected with TFK-1 cells. Results. Sodium valproate inhibited cholangiocarcinoma cell growth by inducing cell cycle arrest, cell differentiation, and apoptosis; sodium valproate effects were independent of autophagy. Tumor growth inhibition was also observed in vivo using TFK-1 xenografts. Conclusion. The in vitro and in vivo outcomes provide preclinical rationale for clinical evaluation of sodium valproate, alone or in combination with other drugs, to improve patient outcome in cholangiocarcinoma.

Yang, Rui; Wu, Yue; Li, Hongbo; Hu, Zouxiao; Chen, Yongjun; Zou, Shengquan

2013-01-01

253

Inhibition of arachidonic acid metabolism in colonic inflammation  

SciTech Connect

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

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

1986-03-01

254

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

255

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

256

Inhibition of intracranial glioma growth by endometrial regenerative cells.  

PubMed

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

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

2009-02-15

257

Inhibition of endogenous reverse transcriptase antagonizes human tumor growth.  

PubMed

Undifferentiated cells and embryos express high levels of endogenous non-telomerase reverse transcriptase (RT) of retroposon/retroviral origin. We previously found that RT inhibitors modulate cell growth and differentiation in several cell lines. We have now sought to establish whether high levels of RT activity are directly linked to cell transformation. To address this possibility, we have employed two different approaches to inhibit RT activity in melanoma and prostate carcinoma cell lines: pharmacological inhibition by two characterized RT inhibitors, nevirapine and efavirenz, and downregulation of expression of RT-encoding LINE-1 elements by RNA interference (RNAi). Both treatments reduced proliferation, induced morphological differentiation and reprogrammed gene expression. These features are reversible upon discontinuation of the anti-RT treatment, suggesting that RT contributes to an epigenetic level of control. Most importantly, inhibition of RT activity in vivo antagonized tumor growth in animal experiments. Moreover, pretreatment with RT inhibitors attenuated the tumorigenic phenotype of prostate carcinoma cells inoculated in nude mice. Based on these data, the endogenous RT can be regarded as an epigenetic regulator of cell differentiation and proliferation and may represent a novel target in cancer therapy. PMID:15806170

Sciamanna, Ilaria; Landriscina, Matteo; Pittoggi, Carmine; Quirino, Michela; Mearelli, Cristina; Beraldi, Rosanna; Mattei, Elisabetta; Serafino, Annalucia; Cassano, Alessandra; Sinibaldi-Vallebona, Paola; Garaci, Enrico; Barone, Carlo; Spadafora, Corrado

2005-06-01

258

Inhibition studies of soybean (Glycine max) urease with heavy metals, sodium salts of mineral acids, boric acid, and boronic acids.  

PubMed

Various inhibitors were tested for their inhibitory effects on soybean urease. The K(i) values for boric acid, 4-bromophenylboronic acid, butylboronic acid, and phenylboronic acid were 0.20 +/- 0.05 mM, 0.22 +/- 0.04 mM, 1.50 +/- 0.10 mM, and 2.00 +/- 0.11 mM, respectively. The inhibition was competitive type with boric acid and boronic acids. Heavy metal ions including Ag(+), Hg(2+), and Cu(2+) showed strong inhibition on soybean urease, with the silver ion being a potent inhibitor (IC(50) = 2.3 x 10(-8) mM). Time-dependent inhibition studies exhibited biphasic kinetics with all heavy metal ions. Furthermore, inhibition studies with sodium salts of mineral acids (NaF, NaCl, NaNO(3), and Na(2)SO(4)) showed that only F(-) inhibited soybean urease significantly (IC(50) = 2.9 mM). Competitive type of inhibition was observed for this anion with a K(i) value of 1.30 mM. PMID:20014894

Kumar, Sandeep; Kayastha, Arvind M

2010-10-01

259

Curcumin inhibits tumor growth and angiogenesis in glioblastoma xenografts.  

PubMed

Among the natural products shown to possess chemopreventive and anticancer properties, curcumin is one of the most potent. In the current study, we investigated the effects of this natural product on the growth of human glioma U-87 cells xenografted into athymic mice. We show here that curcumin administration exerted significant anti-tumor effects on subcutaneous and intracerebral gliomas as demonstrated by the slower tumor growth rate and the increase of animal survival time. While investigating the mechanism of its action in vivo, we observed that curcumin decreased the gelatinolytic activities of matrix metalloproteinase-9. Furthermore, treatment with curcumin inhibited glioma-induced angiogenesis as indicated by the decrease of endothelial cell marker from newly formed vessels and by the diminution of the concentration of hemoglobin in curcumin-treated tumors. We also demonstrate, using an in vitro model of blood-brain barrier, that curcumin can cross the blood-brain barrier to a high level. These are the first results showing that curcumin suppresses tumor growth of gliomas in xenograft models. The mechanisms of the anti-tumor effects of curcumin were related, at least partly, to the inhibition of glioma-induced angiogenesis. PMID:20087857

Perry, Marie-Claude; Demeule, Michel; Régina, Anthony; Moumdjian, Robert; Béliveau, Richard

2010-08-01

260

Exogenous ethylene inhibits sprout growth in onion bulbs  

PubMed Central

Background and Aims Exogenous ethylene has recently gained commercial interest as a sprouting inhibitor of onion bulbs. The role of ethylene in dormancy and sprouting of onions, however, is not known. Methods A cultivar (Allium cepa ‘Copra’) with a true period of dormancy was used. Dormant and sprouting states of onion bulbs were treated with supposedly saturating doses of ethylene or with the ethylene-action inhibitor 1-methylcyclopropene (1-MCP). Initial sprouting was determined during storage at 18 °C by monitoring leaf blade elongation in a specific size class of leaf sheaths. Changes in ATP content and sucrose synthase activity in the sprout leaves, indicators of the sprouting state, were determined. CO2 and ethylene production of onion bulbs during storage were recorded. Key results Exogenous ethylene suppressed sprout growth of both dormant and already sprouting onion bulbs by inhibiting leaf blade elongation. In contrast to this growth-inhibiting effect, ethylene stimulated CO2 production by the bulbs about 2-fold. The duration of dormancy was not significantly affected by exogenous ethylene. However, treatment of dormant bulbs with 1-MCP caused premature sprouting. Conclusions Exogenous ethylene proved to be a powerful inhibitor of sprout growth in onion bulbs. The dormancy breaking effect of 1-MCP indicates a regulatory role of endogenous ethylene in onion bulb dormancy.

Bufler, Gebhard

2009-01-01

261

Bisphosphonate treatment inhibits the growth of prostate cancer cells.  

PubMed

The presence of skeletal metastases in patients suffering from cancer leads to a variety of clinical complications. Bisphosphonates are a class of drugs with a potent bone resorption inhibition activity that have found increasing utility in treating and managing patients with metastatic bone disease. Several clinical trials have demonstrated that bisphosphonates have clinical value in the treatment and management of skeletal metastases derived from advanced prostate cancer. Currently, the mechanism(s) through which bisphosphonates exert their activity is only beginning to be understood. We have studied the effects of bisphosphonate treatment on the growth of prostate cancer cell lines in vitro. Treatment of PC3, DU145, and LNCaP cells with pamidronate or zoledronate significantly reduced the growth of all three cell lines. Using flow cytometry, pamidronate treatment (100 microM) was shown to induce significant amounts of cell death in all three cell lines studied. In contrast, treatment with zoledronate (100 microM) did not induce cell death, instead exerting dramatic effects on cell proliferation, as evidenced by a major increase in cells present in the G0-G1 and S phase. Although both drugs reduced prostate cancer cell growth in the presence of serum, zoledronate was more potent under these conditions, disrupting growth at doses as low as 25 microM in the presence of 5% fetal bovine serum. These results raise the intriguing possibility that the observed clinical utility of bisphosphonates in managing skeletal metastases may in part derive from direct inhibition of prostate cancer cell growth in the bone microenvironment. PMID:11289137

Lee, M V; Fong, E M; Singer, F R; Guenette, R S

2001-03-15

262

Gene expression profiles in t24 human bladder carcinoma cells by inhibiting an l-type amino acid transporter, lat1  

Microsoft Academic Search

Inhibition of LAT1 (L-type amino acid transporter 1 ) activity in tumor cells could be effective in the inhibition of tumor\\u000a cell growth by depriving tumor cells of essential amino acids. Because of the high level of expression of LAT1 in tumor cells,\\u000a LAT1 inhibitors would be useful for anticancer therapy in suppressing tumor growth without affecting normal tissues. In

Shadi Baniasadi; Arthit Chairoungdua; Yuji Iribe; Yoshikatsu Kanai; Hitoshi Endou; Ken-ichi Aisaki; Katsuhide Igarashi; Jun Kanno

2007-01-01

263

Griseofulvin inhibits the growth of adrenocortical cancer cells in vitro.  

PubMed

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

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

2013-04-01

264

Macrokinetics of magnesium sulfite oxidation inhibited by ascorbic acid.  

PubMed

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

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

2013-08-15

265

Insulin-like growth factor binding protein-4 differentially inhibits growth factor-induced angiogenesis.  

PubMed

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

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

2012-01-13

266

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

PubMed

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

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

2014-05-01

267

Kinetics of the inhibition of ascorbic acid browning by sulphite  

Microsoft Academic Search

Despite differences in the structures of aldoses and ascorbic acid, ASA, the non?enzymic browning of the latter involves intermediates similar to those found in Maillard browning. The kinetics of the sulphite?inhibited browning of ASA suggest that, under anaerobic conditions, the rate of reaction of sulphite species, S(IV), is of first order with respect to S(IV). The possibility that S(IV) could

C. G. A. Davies; B. L. Wedzicha

1992-01-01

268

Inhibition of experimental autoimmune uveitis by amino acid copolymers  

Microsoft Academic Search

Glatiramer acetate (GA), a synthetic random amino acid copolymer, poly(Y, E, A, K)n, is widely used for treatment of multiple sclerosis. It inhibits experimental autoimmune encephalomyelitis (EAE) in mice by competition with the antigen and by induction of regulatory T cells. A novel copolymer, poly (F, Y, A, K)n , designated FYAK, was more effective than GA in its immunomodulatory

Hongen Yin; Barbara P. Vistica; Chi-Chao Chan; Jack L. Strominger; Igal Gery

2009-01-01

269

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

2013-08-01

270

Inhibition of melanoma tumor growth in vivo by survivin targeting  

PubMed Central

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

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

2001-01-01

271

Contribution of cinnamic acid analogues in rosmarinic acid to inhibition of snake venom induced hemorrhage.  

PubMed

In our previous paper, we reported that rosmarinic acid (1) of Argusia argentea could neutralize snake venom induced hemorrhagic action. Rosmarinic acid (1) consists of two phenylpropanoids: caffeic acid (2) and 3-(3,4-dihydroxyphenyl)lactic acid (3). In this study, we investigated the structural requirements necessary for inhibition of snake venom activity through the use of compounds, which are structurally related to rosmarinic acid (1). By examining anti-hemorrhagic activity of cinnamic acid analogs against Protobothrops flavoviridis (Habu) venom, it was revealed that the presence of the E-enoic acid moiety (-CH=CH-COOH) was critical. Furthermore, among the compound tested, it was concluded that rosmarinic acid (1) (IC(50) 0.15 ?M) was the most potent inhibitor against the venom. PMID:21388814

Aung, Hnin Thanda; Furukawa, Tadashi; Nikai, Toshiaki; Niwa, Masatake; Takaya, Yoshiaki

2011-04-01

272

Effects of food preservatives on Alternaria alternata growth and tenuazonic acid production.  

PubMed

The effects of different organic acids on Alternaria alternata growth and tenuazonic acid production (TeA) were evaluated. Both TeA pure toxin solution and TeA production in solid medium were considered. Sodium benzoate, potassium sorbate and sodium propionate, all preservatives commonly used by food industry in Argentina, were tested. TeA was stable as pure toxin solution when was treated with the salts of organic acids used. A differential effect was observed when the preservatives were evaluated in relation to A. alternata growth and TeA production in solid medium. Levels above 10 mg/kg of sodium benzoate and potassium sorbate produced a total inhibition of fungal development and toxin biosynthesis. Sodium propionate produced a 59% decrease in A. alternata growth and total inhibition of TeA production only at the highest concentration of preservatives used. PMID:10755134

Combina, M; Dalcero, A M; Varsavsky, E; Chulze, S

1999-10-01

273

Xanthine oxidase inhibits growth of Plasmodium falciparum in human erythrocytes in vitro.  

PubMed Central

Malaria parasites, unable to synthesize purine de novo, use host-derived hypoxanthine preferentially as purine source. In a previous study (1990. J. Biol. Chem. 265:6562-6568), we noted that xanthine oxidase rapidly and completely depleted hypoxanthine in human erythrocytes, not by crossing the erythrocyte membrane, but rather by creating a concentration gradient which facilitated hypoxanthine efflux. We therefore investigated the ability of xanthine oxidase to inhibit growth of FCR-3, a chloroquine-resistant strain of Plasmodium falciparum in human erythrocytes in vitro. Parasites were cultured in human group O+ erythrocytes in medium supplemented, as required, with xanthine oxidase or chloroquine. Parasite viability was assessed by uptake of radiolabeled glycine and adenosine triphosphate-derived purine into protein and nucleic acid, respectively, by nucleic acid accumulation, by L-lactate production, and by microscopic appearance. On average, a 90% inhibition of growth was observed after 72 h of incubation in 20 mU/ml xanthine oxidase. Inhibition was notably greater than that exerted by 10(-7) M chloroquine (less than 10%) over a comparable period. The IC50 for xanthine oxidase was estimated at 0.2 mU/ml, compared to 1.5 x 10(-7) M for chloroquine. Inhibition was completely reversed by excess hypoxanthine, but was unaffected by oxygen radical scavengers, including superoxide dismutase and catalase. The data confirms that a supply of host-derived hypoxanthine is critical for nucleic acid synthesis in P. falciparum, and that depletion of erythrocyte hypoxanthine pools of chloroquine-resistant malaria infection in humans. of chloroquine-resistant malaria infection in humans. Images

Berman, P A; Human, L; Freese, J A

1991-01-01

274

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

PubMed Central

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

2014-01-01

275

XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts.  

PubMed

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

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

2013-02-01

276

Alpha1-antitrypsin inhibits angiogenesis and tumor growth.  

PubMed

Disturbances of the ratio between angiogenic inducers and inhibitors in tumor microenvironment are the driving force behind angiogenic switch critical for tumor progression. Angiogenic inhibitors may vary depending on organismal age and the tissue of origin. We showed that alpha(1)-antitrypsin (AAT), a serine protease inhibitor (serpin) is an inhibitor of angiogenesis, which induced apoptosis and inhibited chemotaxis of endothelial cells. S- and Z-type mutations that cause abnormal folding and defective serpin activity abrogated AAT antiangiogenic activity. Removal of the C-terminal reactive site loop had no effect on its angiostatic activity. Both native AAT and AAT truncated on C-terminus (AATDelta) inhibited neovascularization in the rat cornea and delayed the growth of subcutaneous tumors in mice. Treatment with native AAT and truncated AATDelta, but not control vehicle reduced tumor microvessel density, while increasing apoptosis within tumor endothelium. Comparative analysis of the human tumors and normal tissues of origin showed correlation between reduced local alpha(1)-antitrypsin expression and more aggressive tumor growth. PMID:15316942

Huang, Hanhua; Campbell, Steven C; Nelius, Thomas; Bedford, Dhugal F; Veliceasa, Dorina; Bouck, Noel P; Volpert, Olga V

2004-12-20

277

Erlotinib Inhibits Growth of a Patient-Derived Chordoma Xenograft  

PubMed Central

Chordomas are rare primary bone tumors that occur along the neuraxis. Primary treatment is surgery, often followed by radiotherapy. Treatment options for patients with recurrence are limited and, notably, there are no FDA approved therapeutic agents. Development of therapeutic options has been limited by the paucity of preclinical model systems. We have established and previously reported the initial characterization of the first patient-derived chordoma xenograft model. In this study, we further characterize this model and demonstrate that it continues to resemble the original patient tumor histologically and immunohistochemically, maintains nuclear expression of brachyury, and is highly concordant with the original patient tumor by whole genome genotyping. Pathway analysis of this xenograft demonstrates activation of epidermal growth factor receptor (EGFR). In vitro studies demonstrate that two small molecule inhibitors of EGFR, erlotinib and gefitinib, inhibit proliferation of the chordoma cell line U-CH 1. We further demonstrate that erlotinib significantly inhibits chordoma growth in vivo. Evaluation of tumors post-treatment reveals that erlotinib reduces phosphorylation of EGFR. This is the first demonstration of antitumor activity in a patient-derived chordoma xenograft model and these findings support further evaluation of EGFR inhibitors in this disease.

Siu, I-Mei; Ruzevick, Jacob; Zhao, Qi; Connis, Nick; Jiao, Yuchen; Bettegowda, Chetan; Xia, Xuewei; Burger, Peter C.; Hann, Christine L.; Gallia, Gary L.

2013-01-01

278

Triptolide inhibits the growth and metastasis of solid tumors.  

PubMed

Triptolide (TPL), a diterpenoid triepoxide purified from the Chinese herb Tripterygium wilfordii Hook F, was tested for its antitumor properties in several model systems. In vitro, TPL inhibited the proliferation and colony formation of tumor cells at extremely low concentrations (2-10 ng/ml) and was more potent than Taxol. Likewise, in vivo, treatment of mice with TPL for 2-3 weeks inhibited the growth of xenografts formed by four different tumor cell lines (B16 melanoma, MDA-435 breast cancer, TSU bladder cancer, and MGC80-3 gastric carcinoma), indicating that TPL has a broad spectrum of activity against tumors that contain both wild-type and mutant forms of p53. In addition, TPL inhibited experimental metastasis of B16F10 cells to the lungs and spleens of mice. The antitumor effect of TPL was comparable or superior with that of conventional antitumor drugs, such as Adriamycin, mitomycin, and cisplatin. Importantly, tumor cells that were resistant to Taxol attributable to the overexpression of the multidrug resistant gene 1 were still sensitive to the effects of TPL. Studies on cultured tumor cells revealed that TPL induced apoptosis and reduced the expression of several molecules that regulate the cell cycle. Taken together, these results suggest that TPL has several attractive features as a new antitumor agent. PMID:12533674

Yang, Shanmin; Chen, Jinguo; Guo, Zhen; Xu, Xue-Ming; Wang, Luping; Pei, Xu-Fang; Yang, Jing; Underhill, Charles B; Zhang, Lurong

2003-01-01

279

Lactoferrin inhibits the growth of nasal polyp fibroblasts.  

PubMed

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

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

2010-01-01

280

Inhibition of tumor cell growth by monoterpenes in vitro: evidence of a Ras-independent mechanism of action.  

PubMed

(+)-Limonene (d-limonene) and related monoterpenes show chemopreventive activity against rodent mammary carcinoma and inhibit the growth of cancer cells in vitro. One suggested mechanism for the anti-tumorigenic effect of (+)-limonene is inhibition of the post-translational isoprenylation of growth controlling Ras oncoproteins. We have here examined the growth inhibitory effect of (+)-limonene and other related monoterpenes on PANC-1 pancreas carcinoma cells (carrying a K-ras mutation) and on 12V-H-ras-transformed rat fibroblasts. (+)- and (-)-perillyl alcohol, 7-methyl-perillyl alcohol, (+)-limonene oxide and (+)-perillic acid methyl ester were all found to efficiently inhibit cell growth at 1 mM, whereas (+)-limonene caused an approximately 50% growth reduction at 5 mM. Whereas BZA-5B, an inhibitor of Ras farnesyl transferase, was found to induce morphological reversion of 12V-H-ras-transformed cells, (+)-perillyl alcohol and (+)-limonene did not induce reversion. Furthermore, monoterpenes did not decrease MAP kinase enzyme activity or collagenase promoter activity in PANC-1 cells, two functions known to be down-stream from Ras. We conclude that although effective in inhibiting the growth of tumor cells harboring activated ras oncogenes, limonene and (+)-perillyl alcohol are unlikely to act by inhibiting Ras function. PMID:8826611

Karlson, J; Borg-Karlson, A K; Unelius, R; Shoshan, M C; Wilking, N; Ringborg, U; Linder, S

1996-06-01

281

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

PubMed Central

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

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

2013-01-01

282

Hedgehog pathway inhibition in chondrosarcoma using the smoothened inhibitor IPI-926 directly inhibits sarcoma cell growth.  

PubMed

Hedgehog (Hh) pathway inhibition in cancer has been evaluated in both the ligand-independent and ligand-dependent settings, where Hh signaling occurs either directly within the cancer cells or within the nonmalignant cells of the tumor microenvironment. Chondrosarcoma is a malignant tumor of cartilage in which there is ligand-dependent activation of Hh signaling. IPI-926 is a potent, orally delivered small molecule that inhibits Hh pathway signaling by binding to Smoothened (SMO). Here, the impact of Hh pathway inhibition on primary chondrosarcoma xenografts was assessed. Mice bearing primary human chondrosarcoma xenografts were treated with IPI-926. The expression levels of known Hh pathway genes, in both the tumor and stroma, and endpoint tumor volumes were measured. Gene expression profiling of tumors from IPI-926-treated mice was conducted to identify potential novel Hh target genes. Hh target genes were studied to determine their contribution to the chondrosarcoma neoplastic phenotype. IPI-926 administration results in downmodulation of the Hh pathway in primary chondrosarcoma xenografts, as demonstrated by evaluation of the Hh target genes GLI1 and PTCH1, as well as inhibition of tumor growth. Chondrosarcomas exhibited autocrine and paracrine Hh signaling, and both were affected by IPI-926. Decreased tumor growth is accompanied by histopathologic changes, including calcification and loss of tumor cells. Gene profiling studies identified genes differentially expressed in chondrosarcomas following IPI-926 treatment, one of which, ADAMTSL1, regulates chondrosarcoma cell proliferation. These studies provide further insight into the role of the Hh pathway in chondrosarcoma and provide a scientific rationale for targeting the Hh pathway in chondrosarcoma. PMID:24634412

Campbell, Veronica T; Nadesan, Puviindran; Ali, S Amanda; Wang, Chang Ye Yale; Whetstone, Heather; Poon, Raymond; Wei, Qingxia; Keilty, John; Proctor, Jennifer; Wang, Lauren W; Apte, Suneel S; McGovern, Karen; Alman, Benjamin A; Wunder, Jay S

2014-05-01

283

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

284

Growth inhibitory effects of anthranilic acid and its derivatives against Legionella pneumophila.  

PubMed

Legionella pneumophila is the principal etiologic agent of Legionnaires' disease. We found that the growth of L. pneumophila was markedly inhibited by its own cell lysate and the inhibitory effect was abolished by heat-treatment of the lysate. The genomic library of L. pneumophila was constructed in Escherichia coli and screened to determine the gene involved in the growth inhibition. A clone harboring the gene encoding anthranilate synthase (TrpE), which is involved in tryptophan biosynthesis, exhibited an inhibitory effect on the growth of L. pneumophila. Anthranilic acid exogenously added also exhibited antibacterial activity against L. pneumophila. A series of single-gene-knockout mutants of L. pneumophila lacking tryptophan synthesis genes were constructed and assessed for their susceptibility to anthranilic acid. Although the growth of mutants deficient in anthranilate phosphoribosyltransferase (TrpD) and N-(5'-phosphoribosyl)anthranilate isomerase (TrpF) was not affected by exogenous anthranilic acid, the indole-3-glycerophosphate synthase (TrpC) deficient mutant exhibited an increased susceptibility compared with the parent strain. These observations strongly indicate that 1-(2-carboxyphenylamino)-1'-deoxyribulose-5'-phosphate (CPADR-5'-P), which is an intermediate of tryptophan synthesis from anthranilic acid, is responsible for the growth inhibition of L. pneumophila. PMID:22341575

Sasaki, Takahide; Mizuguchi, Satoru; Honda, Kohsuke

2012-06-01

285

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

286

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

287

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

288

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

PubMed Central

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

Hughes, Julia; Mellows, Graham

1978-01-01

289

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

Microsoft Academic Search

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

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

1993-01-01

290

Effects of Long-Chain Fatty Acids on Growth of Rumen Bacteria †  

PubMed Central

The effects of low concentrations of long-chain fatty acids (palmitic, stearic, oleic, and vaccenic) on the growth of seven species (13 strains) of rumen bacteria were investigated. Except for Bacteroides ruminicola and several strains of Butyrivibrio fibrisolvens, bacterial growth was not greatly affected by either palmitic or stearic acids. In contrast, growth of Selenomonas ruminantium, B. ruminicola, and one strain of B. fibrisolvens was stimulated by oleic acid, whereas the cellulolytic species were markedly inhibited by this acid. Vaccenic acid (trans ?11 18:1) had far less inhibitory effect on the cellulolytic species than oleic acid (cis ?9 18:1). Inclusion of powdered cellulose in the medium appeared to reverse both inhibitory and stimulatory effects of added fatty acids. However, there was little carry-over effect observed when cells were transferred from a medium with fatty acids to one without. Considerable variation in response to added fatty acids was noted among five strains of B. fibrisolvens. In general, exogenous long-chain fatty acids appear to have little, if any, energy-sparing effect on the growth of rumen bacteria.

Maczulak, A. E.; Dehority, B. A.; Palmquist, D. L.

1981-01-01

291

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

292

Inhibition of myeloperoxidase-mediated hypochlorous acid production by nitroxides  

PubMed Central

Tissue damage resulting from the extracellular production of HOCl (hypochlorous acid) by the MPO (myeloperoxidase)-hydrogen peroxide-chloride system of activated phagocytes is implicated as a key event in the progression of a number of human inflammatory diseases. Consequently, there is considerable interest in the development of therapeutically useful MPO inhibitors. Nitroxides are well established antioxidant compounds of low toxicity that can attenuate oxidative damage in animal models of inflammatory disease. They are believed to exert protective effects principally by acting as superoxide dismutase mimetics or radical scavengers. However, we show here that nitroxides can also potently inhibit MPO-mediated HOCl production, with the nitroxide 4-aminoTEMPO inhibiting HOCl production by MPO and by neutrophils with IC50 values of approx. 1 and 6 ?M respectively. Structure–activity relationships were determined for a range of aliphatic and aromatic nitroxides, and inhibition of oxidative damage to two biologically-important protein targets (albumin and perlecan) are demonstrated. Inhibition was shown to involve one-electron oxidation of the nitroxides by the compound I form of MPO and accumulation of compound II. Haem destruction was also observed with some nitroxides. Inhibition of neutrophil HOCl production by nitroxides was antagonized by neutrophil-derived superoxide, with this attributed to superoxide-mediated reduction of compound II. This effect was marginal with 4-aminoTEMPO, probably due to the efficient superoxide dismutase-mimetic activity of this nitroxide. Overall, these data indicate that nitroxides have considerable promise as therapeutic agents for the inhibition of MPO-mediated damage in inflammatory diseases.

Rees, Martin D.; Bottle, Steven E.; Fairfull-Smith, Kathryn E.; Malle, Ernst; Whitelock, John M.; Davies, Michael J.

2014-01-01

293

p8 inhibits the growth of human pancreatic cancer cells and its expression is induced through pathways involved in growth inhibition and repressed by factors promoting cell growth  

PubMed Central

Background p8 is a stress-induced protein with multiple functions and biochemically related to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in pancreatic cancer-derived cells. Methods Expression of p8 was silenced in the human pancreatic cancer cell lines Panc-1 and BxPc-3 by infection with a retrovirus expressing p8 RNA in the antisense orientation. Cell growth was measured in control and p8-silenced cells. Influence on p8 expression of the induction of intracellular pathways promoting cellular growth or growth arrest was monitored. Results p8-silenced cells grew more rapidly than control cells transfected with the empty retrovirus. Activation of the Ras?Raf?MEK?ERK and JNK intracellular pathways down-regulated p8 expression. In addition, the MEK1/2 inhibitor U0126 and the JNK inhibitor SP600125 up-regulates expression of p8. Conversely, p38 or TGF?-1 induced p8 expression whereas the specific p38 inhibitor SB203580 down-regulated p8 expression. Finally, TGF?-1 induction was in part mediated through p38. Conclusions p8 inhibits the growth of human pancreatic cancer cells. p8 expression is induced through pathways involved in growth inhibition and repressed by factors that promote cell growth. These results suggest that p8 belongs to a pathway regulating the growth of pancreatic cancer cells.

Malicet, Cedric; Lesavre, Nathalie; Vasseur, Sophie; Iovanna, Juan L

2003-01-01

294

Functional Amino Acids in Growth, Reproduction, and Health12  

PubMed Central

Amino acids (AA) were traditionally classified as nutritionally essential or nonessential for animals and humans based on nitrogen balance or growth. A key element of this classification is that all nonessential AA (NEAA) were assumed to be synthesized adequately in the body as substrates to meet the needs for protein synthesis. Unfortunately, regulatory roles for AA in nutrition and metabolism have long been ignored. Such conceptual limitations were not recognized until recent seminal findings that dietary glutamine is necessary for intestinal mucosal integrity and dietary arginine is required for maximum neonatal growth and embryonic survival. Some of the traditionally classified NEAA (e.g. glutamine, glutamate, and arginine) play important roles in regulating gene expression, cell signaling, antioxidative responses, and immunity. Additionally, glutamate, glutamine, and aspartate are major metabolic fuels for the small intestine and they, along with glycine, regulate neurological function. Among essential AA (EAA), much emphasis has been placed on leucine (which activates mammalian target of rapamycin to stimulate protein synthesis and inhibit proteolysis) and tryptophan (which modulates neurological and immunological functions through multiple metabolites, including serotonin and melatonin). A growing body of literature leads to a new concept of functional AA, which are defined as those AA that regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of organisms. Both NEAA and EAA should be considered in the classic “ideal protein” concept or formulation of balanced diets to maximize protein accretion and optimize health in animals and humans.

Wu, Guoyao

2010-01-01

295

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

PubMed Central

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

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

2013-01-01

296

Dynamic light scattering study of inhibition of nucleation and growth of hydroxyapatite crystals by osteopontin.  

PubMed

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

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

2013-01-01

297

Bioactive compound from Pseudomonas synxantha inhibits the growth of Mycobacteria.  

PubMed

Tuberculosis is a dreaded disease and the current situation demands new anti-tubercular agent(s) for the management of public health. Towards this direction, we obtained a contaminant organism on a Mycobacterium smegmatis lawn having growth inhibitory activity against the later. In the current study, efforts were targeted to identify this organism and characterize the bioactive compound from this isolate that inhibited the growth of Mycobacteria. The result revealed that the organism is a strain of Pseudomonas synxantha. Biophysical analyses including (1)H and (13)C NMR, ESI-mass spectroscopy, FTIR showed that the bioactive compound is a long chain aliphatic hydrocarbon with a terminal alyl bond and intermediate electronegative atom. The compound exhibited strong growth inhibitory activities against M. smegmatis and Mycobacterium tuberculosis strains H37Ra, H37Rv and BCG. Further experiments showed that both P. synxantha and its secretory metabolites are capable of inducing hemolysis of human blood. Thus the results of this study clearly indicate that the bioactive compound produced by P. Synxantha has biosurfactant activities as well as anti-myco-bacterial properties. PMID:24439826

Mukherjee, Koushik; Mandal, Santanu; Mukhopadhyay, Balaram; Mandal, Nitai Chandra; Sil, Alok Kumar

2014-01-01

298

Aurin tricarboxylic acid inhibits adhesion of platelets to subendothelium.  

PubMed

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

Owens, M R; Holme, S

1996-01-15

299

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

300

Salicylic Acid Inhibits Synthesis of Proteinase Inhibitors in Tomato Leaves Induced by Systemin and Jasmonic Acid.  

PubMed Central

Salicylic acid (SA) and acetylsalicylic acid (ASA), previously shown to inhibit proteinase inhibitor synthesis induced by wounding, oligouronides (H.M. Doherty, R.R. Selvendran, D.J. Bowles [1988] Physiol Mol Plant Pathol 33: 377-384), and linolenic acid (H. Pena-Cortes, T. Albrecht, S. Prat, E.W. Weiler, L. Willmitzer [1993] Planta 191: 123-128), are shown here to be potent inhibitors of systemin-induced and jasmonic acid (JA)-induced synthesis of proteinase inhibitor mRNAs and proteins. The inhibition by SA and ASA of proteinase inhibitor synthesis induced by systemin and JA, as well as by wounding and oligosaccharide elicitors, provides further evidence that both oligosaccharide and polypeptide inducer molecules utilize the octadecanoid pathway to signal the activation of proteinase inhibitor genes. Tomato (Lycopersicon esculentum) leaves were pulse labeled with [35S]methionine, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the inhibitory effects of SA are shown to be specific for the synthesis of a small number of JA-inducible proteins that includes the proteinase inhibitors. Previous results have shown that SA inhibits the conversion of 13S-hydroperoxy linolenic acid to 12-oxo-phytodienoic acid, thereby inhibiting the signaling pathway by blocking synthesis of JA. Here we report that the inhibition of synthesis of proteinase inhibitor proteins and mRNAs by SA in both light and darkness also occurs at a step in the signal transduction pathway, after JA synthesis but preceding transcription of the inhibitor genes.

Doares, S. H.; Narvaez-Vasquez, J.; Conconi, A.; Ryan, C. A.

1995-01-01

301

In vitro Growth Inhibition of Plasmodium falciparum by Sera from Tropical Splenomegaly Syndrome Patients.  

National Technical Information Service (NTIS)

Sera from tropical splenomegaly syndrome(TSS) and non-TSS patients from the same village were examined for their ability to inhibit the in vitro growth of Plasmodium falciparum. Using synchronized malaria cultures, sera from both groups inhibited parasite...

J. R. Campbell S. L. Hoffman B. Leksana L. Kurniawan H. A. Marwoto

1986-01-01

302

Inhibition of acetylcholinesterase by gallic acid- grafted-chitosans  

Microsoft Academic Search

This paper discusses acetylcholinesterase inhibitory properties of gallic acid-grafted-chitosans (GA-g-chitosans) with different grafting ratios. The GA-g-chitosans exhibited potent acetylcholinesterase inhibitory effects in a dose-dependent manner, and their IC50 values ranged from 138.5±0.25 to 397.6±5.2?g\\/mL. The acetylcholinesterase inhibition kinetics of the GA-g-chitosan (I) by Lineweaver–Burk plots showed a decrease in Vmax, whereas Km was not altered, thus suggesting a non-competitive mode

Young-Sook Cho; Se-Kwon Kim; Chang-Bum Ahn; Jae-Young Je

2011-01-01

303

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

304

Inhibition of tumour cell growth by carnosine: some possible mechanisms.  

PubMed

The naturally occurring dipeptide carnosine (?-alanyl-L-histidine) has been shown to inhibit, selectively, growth of transformed cells mediated, at least in part, by depleting glycolytic ATP levels. The mechanism(s) responsible has/have yet to be determined. Here, we discuss a number of probable and/or possible processes which could, theoretically, suppress glycolytic activity which would decrease ATP supply and generation of metabolic intermediates required for continued cell reproduction. Possibilities include effects on (i) glycolytic enzymes, (ii) metabolic regulatory activities, (iii) redox biology, (iv) protein glycation, (v) glyoxalase activity, (vi) apoptosis, (vii) gene expression and (viii) metastasis. It is possible, by acting at various sites that this pluripotent dipeptide may be an example of an endogenous "smart drug". PMID:24292217

Hipkiss, Alan R; Gaunitz, Frank

2014-02-01

305

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

2013-01-01

306

Inhibition of growth of Toxoplasma gondii by qinghaosu and derivatives.  

PubMed

The antimalarial compound qinghaosu (artemisinin) was tested in vitro for the ability to inhibit plaque formation by Toxoplasma gondii in fibroblasts. Qinghaosu at 0.4 microgram/ml for 5 days eliminated all plaques and microscopic foci of T. gondii. At 1.3 micrograms/ml for 14 days, qinghaosu completely eliminated T. gondii. Pretreatment of host cells or T. gondii with qinghaosu had no effect on T. gondii growth. There was no apparent toxicity to human fibroblasts in long-term studies. Of the six qinghaosu derivatives tested, dihydroqinghaosu, 1-propyl-ether-qinghaosu, and 1-butyl-ether-qinghaosu were comparable to qinghaosu. Ethyl-ether-qinghaosu (arteether) and sec-butyl-ether-qinghaosu were more effective. Methyl-ether-qinghaosu (artemether) was the most effective, with a potency approximately 10-fold greater than that of qinghaosu. PMID:2291661

Ke, O Y; Krug, E C; Marr, J J; Berens, R L

1990-10-01

307

Growth of Campylobacter in media supplemented with organic acids.  

PubMed

The growth of Campylobacter spp. in media supplemented with organic acids was examined. A Bioscreen C Microbiology Reader was used to measure growth of cultures incubated at 37 degrees C for 48 h in a tryptose-yeast extract basal broth medium and in basal broth supplemented with 10, 20, 30, 40, or 50 mM citric, fumaric, lactic, malic, or succinic acid. Growth of three of six isolates was significantly greater (P < or = 0.05) in media supplemented with 20 to 50 mM citric acid than in nonsupplemented media, growth of five of six isolates was significantly greater in media supplemented with 10 to 50 mM succinic acid than in nonsupplemented media, and growth of six of six isolates was significantly greater in media supplemented with 10 to 50 mM fumaric or malic acid or with 20 to 50 mM lactic acid than in nonsupplemented media. Isolates were also cultured in basal media supplemented with a mixture of 10, 20, 30, 40, or 50 mM fumaric, malic, lactic, and succinic acids. Results indicated that the growth of all Campylobacter isolates was significantly greater in media supplemented with mixtures containing each of these organic acids at 10 to 40 mM than in nonsupplemented media. These findings indicate that in vitro growth of Campylobacter spp. may be significantly enhancedin media supplemented with organic acids that support the growth of these bacteria. PMID:16416898

Hinton, Arthur

2006-01-01

308

Anticancer agent E7070 inhibits amino acid and uracil transport in fission yeast.  

PubMed

E7070 is a novel sulfonamide anticancer agent that inhibits cell cycle progression in G1 in mammalian cells, but its action targets are not known. We recently employed the genetically amenable fission yeast Schizosaccharomyces pombe as a model organism to search for its targets. Here, we show that E7070 inhibits imports of amino acid and uracil into S. pombe cells. Unlike their prototrophic counterparts, leucine- and uracil-auxotrophic strains are sensitive to E7070 and are unable to proliferate with a delayed G1-S transition in low-glucose yeast extract-polypeptone medium containing this drug because this chemical markedly inhibits the uptake of leucine and uracil in low glucose medium. Furthermore, addition of leucine or uracil to the culture medium or overexpression of genes encoding an amino acid or uracil transporter suppresses the E7070-imposed growth inhibition of these auxotrophic strains. Thus, some of the molecular targets for E7070 action in S. pombe are likely to be leucine and uracil transporters. PMID:11723232

Tsukahara, K; Watanabe, T; Hata-Sugi, N; Yoshimatsu, K; Okayama, H; Nagasu, T

2001-12-01

309

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

PubMed Central

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

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

2014-01-01

310

Inhibition of intramacrophage growth of Penicillium marneffei by 4-aminoquinolines.  

PubMed

The antimicrobial activities of chloroquine (CQ) and several 4-aminoquinoline drugs were tested against Penicillium marneffei, an opportunistic fungus that invades and grows inside macrophages and causes disseminated infection in AIDS patients. Human THP1 and mouse J774 macrophages were infected in vitro with P. marneffei conidia and treated with different doses of drugs for 24 to 48 h followed by cell lysis and the counting of P. marneffei CFU. CQ and amodiaquine exerted a dose-dependent inhibition of fungal growth, whereas quinine and artemisinin were fungistatic and not fungicidal. The antifungal activity of CQ was not due to an impairment of fungal iron acquisition in that it was not reversed by the addition of iron nitrilotriacetate, FeCl3, or iron ammonium citrate. Perl's staining indicated that CQ did not alter the ability of J774 cells to acquire iron from the medium. Most likely, CQ's antifungal activity is due to an increase in the intravacuolar pH and a disruption of pH-dependent metabolic processes. Indeed, we demonstrate that (i) bafilomycin A1 and ammonium chloride, two agents known to alkalinize intracellular vesicles by different mechanisms, were inhibitory as well and (ii) a newly synthesized 4-amino-7-chloroquinoline molecule (compound 9), lacking the terminal amino side chain of CQ that assists in drug accumulation, did not inhibit P. marneffei growth. These results suggest that CQ has a potential for use in prophylaxis of P. marneffei infections in human immunodeficiency virus-infected patients in countries where P. marneffei is endemic. PMID:11302809

Taramelli, D; Tognazioli, C; Ravagnani, F; Leopardi, O; Giannulis, G; Boelaert, J R

2001-05-01

311

Inhibition by lipiarmycin of bacteriophage growth in Bacillus subtilis.  

PubMed Central

We have used lipiarmycin, a specific inhibitor of initiation of transcription, to study the role of host RNA polymerase in the transcription programs of various phages of Bacillus subtilis. Unlike rifampin, lipiarmycin preferentially inhibits transcription dependent on the sigma subunit of RNA polymerase because it inactivates holoenzyme at a much greater rate than it does core enzyme. With phage SP01, addition of lipiarmycin at a middle-to-late time of infection did not inhibit phage production even though phage production was sensitive to addition of rifampin at that time. This result is consistent with the notion that unmodified host RNA polymerase holoenzyme becomes dispensable after transcription of early classes of SP01 genes, even though host core enzyme is required for synthesis of all classes of phage RNA. SP01-modified forms of RNA polymerase, which lack sigma subunit but contain phage-coded polypeptides and are able to transcribe middle and late genes, were resistant to lipiarmycin in vitro. For phage phi 105, phage development was sensitive to both lipiarmycin and rifampin in wild-type cells and resistant to both drugs in resistant mutant cells, leading to the conclusion that the activity of host holoenzyme was required for phage RNA synthesis. Growth of phage PBS2, which was resistant to rifampin, was sensitive to the addition of lipiarmycin at early times of infection of a wild-type host strain. In a lipiarmycin-resistant mutant host, PBS2 growth was resistant to lipiarmycin. This result suggests that host holoenzyme plays a previously unanticipated role in transcription of PBS2 genes.

Osburne, M S; Sonenshein, A L

1980-01-01

312

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

313

Mechanism of inhibition of tumour growth by aspirin and indomethacin.  

PubMed Central

The growth of a 3-methylcholanthrene-induced fibrosarcoma of C3H mice was inhibited by aspirin and indomethacin. While the tumour contained relatively high concentrations of PGE2-like material, that were markedly diminished by indomethacin treatment, our results did not confirm the recently proposed hypothesis that the anti-tumour effect arises from a restoration of depressed immune function. For example, mice that had completely eliminated their tumours under indomethacin administration were not immune to rechallenge. The tumour-bearing animals were not non-specifically immunodepressed, as their splenic PFC responses against SRBC were enhanced. However, while indomethacin augmented the PFC response in normal mice, this adjuvant effect was depressed in tumour-bearing animals. The spleen-cell PHA responses of tumour bearers were severely depressed, and such cells suppressed the PHA response of normal cells. Only after prolonged indomethacin treatment did animals (with comparable tumour burdens) show weak PHA responses and somewhat diminished suppressive activity. Possible alternative mechanisms, such as direct cytotoxicity, or inhibition of inflammation, phosphodiesterase activity, blood coagulation or calcium availability were not implicated (nor definitively excluded) in the anti-tumour effect. Images Fig. 2

Lynch, N. R.; Castes, M.; Astoin, M.; Salomon, J. C.

1978-01-01

314

Inhibition of microbial growth on chitosan membranes by plasma treatment.  

PubMed

The use of polymeric medical devices has stimulated the development of new sterilization methods. The traditional techniques rely on ethylene oxide, but there are many questions concerning the carcinogenic properties of the ethylene oxide residues adsorbed on the materials after processing. Another common technique is the gamma irradiation process, but it is costly, its safe operation requires an isolated site, and it also affects the bulk properties of the polymers. The use of gas plasma is an elegant alternative sterilization technique. The plasma promotes efficient inactivation of the microorganisms, minimizes damage to the materials, and presents very little danger for personnel and the environment. In this study we used plasma for microbial inhibition of chitosan membranes. The membranes were treated with oxygen, methane, or argon plasma for different time periods (15, 30, 45, or 60 min). For inhibition of microbial growth with oxygen plasma, the time needed was 60 min. For the methane plasma, samples were successfully treated after 30, 45, and 60 min. For argon plasma, all treatment periods were effective. PMID:24251774

de Oliveira Cardoso Macêdo, Marina; de Macêdo, Haroldo Reis Alves; Gomes, Dayanne Lopes; de Freitas Daudt, Natália; Rocha, Hugo Alexandre Oliveira; Alves, Clodomiro

2013-11-01

315

Hyperbaric hyperoxia reversibly inhibits erythrocyte phospholipid fatty acid turnover  

NASA Technical Reports Server (NTRS)

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

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

1987-01-01

316

Boric acid inhibits germination and colonization of Saprolegnia spores in vitro and in vivo.  

PubMed

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

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

2014-01-01

317

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

PubMed Central

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

Ali, Shimaa E.; Thoen, Even; Evensen, ?ystein; Skaar, Ida

2014-01-01

318

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

PubMed

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

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

2002-01-01

319

Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice  

PubMed Central

Recent studies have shown that a tumor-supportive microenvironment is characterized by high levels of pro-inflammatory and pro-angiogenic eicosanoids derived from omega-6 (n?6) arachidonic acid (AA). Although the metabolic pathways (COX, LOX, and P450) that generate these n?6 AA eicosanoids have been targeted, the role of endogenous AA production in tumorigenesis remains unexplored. Delta-6 desaturase (D6D) is the rate-limiting enzyme responsible for the synthesis of n?6 AA and increased D6D activity can lead to enhanced n?6 AA production. Here, we show that D6D activity is upregulated during melanoma and lung tumor growth and that suppressing D6D activity, either by RNAi knockdown or a specific D6D inhibitor, dramatically reduces tumor growth. Accordingly, the content of AA and AA-derived tumor-promoting metabolites is significantly decreased. Angiogenesis and inflammatory status are also reduced. These results identify D6D as a key factor for tumor growth and as a potential target for cancer therapy and prevention.

He, Chengwei; Qu, Xiying; Wan, Jianbo; Rong, Rong; Huang, Lili; Cai, Chun; Zhou, Keyuan; Gu, Yan; Qian, Steven Y.; Kang, Jing X.

2012-01-01

320

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

PubMed

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

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

2005-02-23

321

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

PubMed Central

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

Ammon, Helmut V.; Phillips, Sidney F.

1974-01-01

322

Inhibition of the growth of Neisseria meningitidis by reduced ferritin and other iron-binding agents.  

PubMed Central

Serogroups of N. meningitidis were characterized as virulent or avirulent according to their capacity to establish meningococcal infection in mice. An agar plate diffusion technique demonstrated that iron had a definite growth-supporting role for both of these meningococcal types. The avirulent strains could use ionic or chelated iron as well as the virulent strains. Iron-reversible growth inhibition occurred to the same extent for both bacterial types in the presence of the synthetic iron-chelating agents Desferal and ethylenediamine-di-orthohydroxy phenylacetic acid. A difference in response was demonstrated for these bacterial types when grown in the presence of various iron-binding proteins from animal body fluids and tissues. The growth of the avirulent strain was inhibited to a greater degree by egg white conalbumin. The humoral iron-binding protein transferrin showed a significant inhibitory capacity only when used in conjunction with bicarbonate. Under conditions of increased iron saturation of this protein, the avirulent strain was inhibited to the furthest extent. In the presence of ferritin, the cellular iron-binding protein, which had been reduced, inhibition of the growth of either strain type did not occur on iron-poor media (less than 5 micrograms/100 ml). However, with the incorporation of iron into the media, the inhibitory effect of the protein became evident. As the concentration of iron increased, the inhibition increased to a certain level and subsequently declined. A substantial difference in the ability of the avirulent type to grow in the presence of reduced horse spleen ferritin was observed. For this microorganism, a correlation appears to exist between the capacity to grow by utilizing the available iron in the presence of reduced ferritin and the ability to establish infection. The host protein ferritin, in the reduced state, apart from simply being a storage protein for iron, can prevent the growth of a procaryotic organism. Our experiments suggest a role for ferritin in the prevention of emningococcal disease. A cehmotherapeutic potential for Desferal is also implied. Images

Calver, G A; Kenny, C P; Kushner, D J

1979-01-01

323

A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth.  

PubMed

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in angiogenesis, survival, metastasis, drug resistance, and glucose metabolism. Elevated expression of the alpha-subunit of HIF-1 (HIF-1alpha), which occurs in response to hypoxia or activation of growth factor pathways, is associated with poor prognosis in many types of cancer. Therefore, down-regulation of HIF-1alpha protein by RNA antagonists may control cancer growth. EZN-2968 is a RNA antagonist composed of third-generation oligonucleotide, locked nucleic acid, technology that specifically binds and inhibits the expression of HIF-1alpha mRNA. In vitro, in human prostate (15PC3, PC3, and DU145) and glioblastoma (U373) cells, EZN-2968 induced a potent, selective, and durable antagonism of HIF-1 mRNA and protein expression (IC(50), 1-5 nmol/L) under normoxic and hypoxic conditions associated with inhibition of tumor cell growth. Additionally, down-regulation of HIF-1alpha protein by EZN-2968 led to reduction of its transcriptional targets and of human umbilical vein endothelial cell tube formation. In vivo, administration of EZN-2968 to normal mice led to specific, dose-dependent, and highly potent down-regulation of endogenous HIF-1alpha and vascular endothelial growth factor in the liver. The effect can last for days after administration of single dose of EZN-2968 and is associated with long residence time of locked nucleic acid in certain tissues. In efficacy studies, tumor reduction was found in nude mice implanted with DU145 cells treated with EZN-2968. Ongoing phase I studies of EZN-2968 in patients with advanced malignancies will determine optimal dose and schedule for the phase II program. PMID:18974394

Greenberger, Lee M; Horak, Ivan D; Filpula, David; Sapra, Puja; Westergaard, Majken; Frydenlund, Henrik F; Albaek, Charlotte; Schrøder, Henrik; Ørum, Henrik

2008-11-01

324

Ferrous iron oxidation by Thiobacillus ferrooxidans: inhibition with benzoic acid, sorbic acid, and sodium lauryl sulfate  

SciTech Connect

Thiobacillus ferrooxidans promote indirect oxidation of pyrite through the catalysis of the oxidation of ferrous iron to ferric iron, which is an effective oxidant of pyrite. These bacteria also may catalyze direct oxidation of pyrite by oxygen. A number of organic compounds, under laboratory conditions, can apparently inhibit both the oxidation of ferrous iron to ferric iron by T. ferrooxidans and the weathering of pyritic material by mixed cultures of acid mine drainage microorganisms. In this study, benzoic acid, sorbic acid, and sodium lauryl sulfate at low concentrations (5 to 10 mg/liter) each effectively inhibited bacterial oxidation of ferrous iron in batch cultures of Thiobacillus ferrooxidans. The rate of chemical oxidation of ferrous iron in low-pH, sterile batch reactors was not substantially affected at the tested concentrations (5 to 50 mg/liter) of any of the compounds.

Onysko, S.J.; Kleinmann, R.L.P.; Erickson, P.M.

1984-07-01

325

A Class of Pantothenic Acid Analogs Inhibits Plasmodium falciparum Pantothenate Kinase and Represses the Proliferation of Malaria Parasites†  

PubMed Central

The growth and proliferation of the human malaria parasite Plasmodium falciparum are dependent on the parasite's ability to obtain essential nutrients. One nutrient for which the parasite has an absolute requirement is the water-soluble vitamin pantothenic acid (vitamin B5). In this study, a series of pantothenic acid analogs which retain the 2,4-dihydroxy-3,3-dimethylbutyramide core of pantothenic acid but deviate in structure from one another and from pantothenic acid in the nature of the substituent attached to the amide nitrogen were synthesized using an efficient single-step synthetic route. Eight of 10 analogs tested inhibited the proliferation of intraerythrocytic P. falciparum parasites in vitro, doing so with 50% inhibitory concentrations between 15 and 200 ?M. The compounds were generally selective, inhibiting the proliferation of a human cell line (the Jurkat cell line) only at concentrations severalfold higher than those required for inhibition of parasite growth. It was demonstrated that compounds in this series inhibited the phosphorylation of pantothenic acid by pantothenate kinase, the first step in the parasite's biosynthesis of the essential enzyme cofactor coenzyme A, doing so competitively, with Ki values in the nanomolar range.

Spry, Christina; Chai, Christina L. L.; Kirk, Kiaran; Saliba, Kevin J.

2005-01-01

326

A class of pantothenic acid analogs inhibits Plasmodium falciparum pantothenate kinase and represses the proliferation of malaria parasites.  

PubMed

The growth and proliferation of the human malaria parasite Plasmodium falciparum are dependent on the parasite's ability to obtain essential nutrients. One nutrient for which the parasite has an absolute requirement is the water-soluble vitamin pantothenic acid (vitamin B5). In this study, a series of pantothenic acid analogs which retain the 2,4-dihydroxy-3,3-dimethylbutyramide core of pantothenic acid but deviate in structure from one another and from pantothenic acid in the nature of the substituent attached to the amide nitrogen were synthesized using an efficient single-step synthetic route. Eight of 10 analogs tested inhibited the proliferation of intraerythrocytic P. falciparum parasites in vitro, doing so with 50% inhibitory concentrations between 15 and 200 microM. The compounds were generally selective, inhibiting the proliferation of a human cell line (the Jurkat cell line) only at concentrations severalfold higher than those required for inhibition of parasite growth. It was demonstrated that compounds in this series inhibited the phosphorylation of pantothenic acid by pantothenate kinase, the first step in the parasite's biosynthesis of the essential enzyme cofactor coenzyme A, doing so competitively, with K(i) values in the nanomolar range. PMID:16251308

Spry, Christina; Chai, Christina L L; Kirk, Kiaran; Saliba, Kevin J

2005-11-01

327

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

PubMed

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

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

2013-11-15

328

Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors.  

PubMed

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. PMID:23110215

Pathi, Satya; Jutooru, Indira; Chadalapaka, Gayathri; Nair, Vijayalekshmi; Lee, Syng-Ook; Safe, Stephen

2012-01-01

329

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

330

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 ...

331

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

SciTech Connect

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

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

2007-04-15

332

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

PubMed

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

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

2014-03-01

333

Growth inhibition of Streptococcus mutans and Leuconostoc mesenteroides by sodium fluoride and ionic tin.  

PubMed Central

Sodium fluoride caused inhibition of growth rate and growth levels of Streptococcus mutans with glucose as the primary energy and carbon source. Stannous fluoride increased growth lag nad caused a much greater inhibition of growth rate than did sodium fluoride. Neither compound was found to be bactericidal when culture viability was measured after 6 days of incubation. Leuconostoc mesenteroides, which lacks a phosphotransferase system for sugar transport, showed less inhibition of growth rate with both inhibitors than did S. mutans, which possesses a phosphotransferase system. Metabolism of glucose or lactose which requires enolase activity shoed sodium fluoride inhibition, whereas metabolism of arginine or pyruvate does not involve enolase activity and showed no inhibition of growth.

Yost, K G; VanDemark, P J

1978-01-01

334

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

PubMed

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

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

2012-12-01

335

Nucleic acid scavengers inhibit thrombosis without increasing bleeding  

PubMed Central

Development of effective, yet safe, antithrombotic agents has been challenging because such agents increase the propensity of patients to bleed. Recently, naturally occurring polyphosphates such as extracellular DNA, RNA, and inorganic polyphosphates have been shown to activate blood coagulation. In this report, we evaluate the anticoagulant and antithrombotic activity of nucleic acid-binding polymers in vitro and in vivo. Such polymers bind to DNA, RNA, and inorganic polyphosphate molecules with high affinity and inhibit RNA- and polyphosphate-induced clotting and the activation of the intrinsic pathway of coagulation in vitro. Moreover, [NH2(CH2)2NH2]?(G = 3);dendri PAMAM(NH2)32 (PAMAM G-3) prevents thrombosis following carotid artery injury and pulmonary thromboembolism in mice without significantly increasing blood loss from surgically challenged animals. These studies indicate that nucleic acid-binding polymers are able to scavenge effectively prothrombotic nucleic acids and other polyphosphates in vivo and represent a new and potentially safer class of antithrombotic agents.

Jain, Shashank; Pitoc, George A.; Holl, Eda K.; Zhang, Ying; Borst, Luke; Leong, Kam W.; Lee, Jaewoo; Sullenger, Bruce A.

2012-01-01

336

Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N?nitrosation  

PubMed Central

Background The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre?carcinogen present in saliva, can be converted to nitrosating species and N?nitroso compounds by acidification at low gastric pH in the presence of thiocyanate. Aims To assess the effect of lipid and ascorbic acid on the nitrosative chemistry under conditions simulating the human proximal stomach. Methods The nitrosative chemistry was modelled in vitro by measuring the nitrosation of four secondary amines under conditions simulating the proximal stomach. The N?nitrosamines formed were measured by gas chromatography–ion?trap tandem mass spectrometry, while nitric oxide and oxygen levels were measured amperometrically. Results In absence of lipid, nitrosative stress was inhibited by ascorbic acid through conversion of nitrosating species to nitric oxide. Addition of ascorbic acid reduced the amount of N?nitrosodimethylamine formed by fivefold, N?nitrosomorpholine by >1000?fold, and totally prevented the formation of N?nitrosodiethylamine and N?nitrosopiperidine. In contrast, when 10% lipid was present, ascorbic acid increased the amount of N?nitrosodimethylamine, N?nitrosodiethylamine and N?nitrosopiperidine formed by approximately 8?, 60? and 140?fold, respectively, compared with absence of ascorbic acid. Conclusion The presence of lipid converts ascorbic acid from inhibiting to promoting acid nitrosation. This may be explained by nitric oxide, formed by ascorbic acid in the aqueous phase, being able to regenerate nitrosating species by reacting with oxygen in the lipid phase.

Combet, E; Paterson, S; Iijima, K; Winter, J; Mullen, W; Crozier, A; Preston, T; McColl, K E L

2007-01-01

337

Targeting Insulin-Like Growth Factor 1 Receptor Inhibits Pancreatic Cancer Growth and Metastasis  

PubMed Central

Pancreatic cancer is one of the most lethal cancers. Increasing incidence and mortality indicates that there is still much lacking in detection and management of the disease. This is partly due to a lack of specific symptoms during early stages of the disease. Several growth factor receptors have been associated with pancreatic cancer. Here, we have investigated if an RNA interference approach targeted to IGF-IR could be effective and efficient against pancreatic cancer growth and metastasis. For that, we evaluated the effects of IGF-1R inhibition using small interfering RNA (siRNAs) on tumor growth and metastasis in HPAC and PANC-1 pancreatic cancer cell lines. We found that silencing IGF-1R inhibits pancreatic cancer growth and metastasis by blocking key signaling pathways such AKT/PI3K, MAPK, JAK/STAT and EMT. Silencing IGF-1R resulted in an anti-proliferative effect in PANC-1 and HPAC pancreatic cancer cell lines. Matrigel invasion, transwell migration and wound healing assays also revealed a role for IGF-1R in metastatic properties of pancreatic cancer. These results were further confirmed using Western blotting analysis of key intermediates involved in proliferation, epithelial mesenchymal transition, migration, and invasion. In addition, soft agar assays showed that silencing IGF-1R also blocks the colony forming capabilities of pancreatic cancer cells in vitro. Western blots, as well as, flow cytometric analysis revealed the induction of apoptosis in IGF-1R silenced cells. Interestingly, silencing IGF-1R also suppressed the expression of insulin receptor ?. All these effects together significantly control pancreatic cancer cell growth and metastasis. To conclude, our results demonstrate the significance of IGF-1R in pancreatic cancer.

Subramani, Ramadevi; Lopez-Valdez, Rebecca; Arumugam, Arunkumar; Nandy, Sushmita; Boopalan, Thiyagarajan; Lakshmanaswamy, Rajkumar

2014-01-01

338

Acid adaptation does not promote survival or growth of Listeria monocytogenes on fresh beef following acid and nonacid decontamination treatments.  

PubMed

The objective of this study was to evaluate the survival and growth of acid-adapted and nonadapted Listeria monocytogenes inoculated onto fresh beef subsequently treated with acid or nonacid solutions. Beef slices (2.5 by 5 by 1 cm) from top rounds were inoculated with acid-adapted or nonadapted L. monocytogenes (4.6 to 5.0 log CFU/cm2) and either left untreated (control) or dipped for 30 s in water at 55 degrees C, water at 75 degrees C, 2% lactic acid at 55 degrees C, or 2% acetic acid at 55 degrees C. The beef slices were vacuum packaged and stored at 4 or 10 degrees C and were analyzed after 0, 7, 14, 21, and 28 days of storage. Dipping in 75 degrees C water, lactic acid, and acetic acid resulted in immediate pathogen reductions of 1.4 to 2.0, 1.8 to 2.6, and 1.4 to 2.4 log CFU/cm2, respectively. After storage at 10 degrees C for 28 days, populations of L. monocytogenes on meat treated with 55 degrees C water increased by ca. 1.6 to 1.8 log CFU/cm2. The pathogen remained at low population levels (1.6 to 2.8 log CFU/cm2) on acid-treated meat, whereas populations on meat treated with 75 degrees C water increased rapidly, reaching levels of 3.6 to 4.6 log CFU/cm2 by day 14. During storage at 4 degrees C, there was no growth of the pathogen for at least 21 days in samples treated with 55 and 75 degrees C water, and periods of no growth were longer for acid-treated samples. There were no differences between acid-adapted and nonadapted organisms across treatments with respect to survival or growth. In conclusion, the dipping of meat inoculated with L. monocytogenes into acid solutions reduced and then inhibited the growth of the pathogen during storage at 4 and 10 degrees C, while dipping in hot water allowed growth despite initial reductions in pathogen contamination. The results of this study indicate a residual activity of acid-based decontamination treatments compared with water-based treatments for refrigerated (4 degrees C) or temperature-abused (10 degrees C) lean beef tissue in vacuum packages, and these results also indicate that this activity may not be counteracted by prior acid adaptation of L. monocytogenes. PMID:12800998

Ikeda, J S; Samelis, J; Kendall, P A; Smith, G C; Sofos, J N

2003-06-01

339

Furfural inhibits growth by limiting sulfur assimilation in ethanologenic Escherichia coli strain LY180.  

PubMed

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

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

2009-10-01

340

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

SciTech Connect

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

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

2012-07-13

341

MicroRNA-320 inhibits osteosarcoma cells proliferation by directly targeting fatty acid synthase.  

PubMed

Increasing evidence has demonstrated that small noncoding microRNAs (miRNAs) could contribute to cancer development and progression. Besides, they are differentially expressed in human tumor tissues. In the current study, we found that miR-320 was significantly downregulated in human osteosarcoma tissues, compared with adjacent normal tissues. Introduction of miR-320 mimics into U2OS and MG63 cells inhibited cell proliferation, while cell apoptosis rate remained unaltered. Additionally, miR-320 overexpression could also suppress tumor growth in the nude mice. At the molecular level, our results further revealed that the expression of fatty acid synthase (FASN), a key enzyme for de novo biosynthesis of fatty acids, was negatively regulated by miR-320. Therefore, our results suggest that miR-320 may act as a tumor suppressor for osteosarcoma. PMID:24390663

Cheng, Chi; Chen, Zhen-Qiang; Shi, Xue-Tao

2014-05-01

342

Inhibition of Translation Initiation Mediates the Anticancer Effect of the n-3 Polyunsaturated Fatty Acid Eicosapentaenoic Acid1  

Microsoft Academic Search

Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid that is abundant in the fish-based diets of populations that exhibit a remarkably low incidence of cancer, exerts anticancer activity in vitro and in animal models of experimental cancer. Here we define the molecular basis for the anticancer effects of EPA. EPA inhibits cell division by inhibiting trans- lation initiation. This is

Sangeetha S. Palakurthi; Rudolf Fluckiger; Hussein Aktas; Arun K. Changolkar; Aliakbar Shahsafaei; Silvia Harneit; Ergin Kilic; Jose A. Halperin

2000-01-01

343

Inhibition of the maximum specific growth and fermentation rate of Zymomonas mobilis by ethanol  

Microsoft Academic Search

The inhibition of the maximum specific growth and fermentation rate of Zymomonas mobilis by ethanol was studied in turbidostat cultures at constant and stepwise changed ethanol concentrations. Up to 50 g\\/l ethanol, the inhibition kinetics can be approximated by a linear relationship between the specific growth rate and the ethanol concentration. Above this level, deviations from this linearity are observed.

I. M. L. Joebses; J. A. Roels

1986-01-01

344

Differentiation of F38 mycoplasmas causing contagious caprine pleuropneumonia with a growth-inhibiting monoclonal antibody.  

PubMed Central

Monoclonal antibody WM-25 inhibited the in vitro growth of 13 F38 isolates from goats with contagious caprine pleuropneumonia but not 7 heterologous mycoplasma isolates representing four different species. In contrast to results with polyclonal antisera, growth inhibition by monoclonal antibody WM-25 was specific for F38 mycoplasma isolates and constituted a reliable means of distinguishing F38 from other mycoplasmas.

Rurangirwa, F R; McGuire, T C; Musoke, A J; Kibor, A

1987-01-01

345

Peroxynitrite modulates acidic fibroblast growth factor (FGF-1) activity.  

PubMed

To establish peroxynitrite (ONOO(-)) as a mediator of acidic fibroblast growth factor (FGF-1) function, preparations of recombinant human FGF-1 were treated with the pro-oxidant in vitro and identified amino acid modifications were correlated with biologic activity. The sequence of FGF-1 amino acid modifications induced by increasing concentrations of ONOO(-) was from cysteine oxidation to dityrosine formation, and to tyrosine/tryptophan nitration. Low steady-state ONOO(-) concentrations (10-50 microM) induced formation of dityrosine, which involved less than 0.1% of the total tyrosines. Treatment of FGF-1 with ONOO(-) induced a dose-dependent (10-50 microM) loss of sulfhydryl groups that correlated with formation of reducible (dithiothreitol, arsenite) FGF-1 aggregates containing 50% latent biologic activity. Treatment with 0.1-0.5mM ONOO(-) induced increasing formation of non-reducible, inactivated FGF-1 structures. Combination of real-time spectral analysis and electrospray mass spectroscopy revealed that six residues (Y29, Y69, Y108, Y111, Y139, and W121) were nitrated by ONOO(-). ONOO(-) treatment (0.1mM) of an active FGF-1 mutant (cysteines converted to serines) induced dose-dependent, non-reversible inhibition of biologic activity that correlated with nitration of Y108 and Y111, both of which reside within a conserved domain encompassing the putative FGF-1 receptor binding site. Collectively, these observations predict a role for low levels of ONOO(-) during secretion of FGF-1 as an extracellular complex containing latent biologic activity. High steady-state levels of ONOO(-) may induce extensive cysteine oxidation, critical tyrosine nitration, and non-reversible inactivation of FGF-1, a potential inhibitory feedback mechanism restoring cellular homeostatis during the resolution of inflammation and repair. PMID:14592461

Bagnasco, Patricia; MacMillan-Crow, Lee Ann; Greendorfer, Jessica S; Young, Carlton J; Andrews, Lori; Thompson, John A

2003-11-15

346

A novel biological role of dehydroascorbic acid: Inhibition of Na(+)-dependent transport of ascorbic acid.  

PubMed

A U937 cell clone, in which low micromolar concentrations of ascorbic acid (AA) and dehydroascorbic acid (DHA) are taken up at identical rates, was used to investigate possible interactions between transport systems mediating cellular uptake of the two forms of the vitamin. Results obtained with different experimental approaches showed that DHA potently and reversibly inhibits AA uptake through Na(+)-AA cotransporters. Hence, a progressive increase in extracellular DHA concentrations in the presence of a fixed amount of AA caused an initial decrease in the net amount of vitamin C accumulated, and eventually, at higher levels, it caused an accumulation of the vitamin solely based on DHA uptake through hexose transporters. DHA-dependent inhibition of AA uptake was also detected in various other cell types. Taken together, our results provide evidence of a novel biological effect mediated by concentrations of DHA compatible with those produced at inflammatory sites. PMID:24769194

Fiorani, Mara; Azzolini, Catia; Guidarelli, Andrea; Cerioni, Liana; Cantoni, Orazio

2014-06-01

347

Inhibition of Trypanosoma cruzi growth by medical plant extracts.  

PubMed

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

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

2002-12-01

348

Chinese medicinal herbs inhibit growth of murine renal cell carcinoma.  

PubMed

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

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

1994-01-01

349

Antigen forks: bispecific reagents that inhibit cell growth by binding selected pairs of tumor antigens  

Microsoft Academic Search

Bispecific antibodies of a new category, termed “antigen forks”, were constructed by crosslinking antibodies that recognized pairs of distinct tumor cell surface antigens. At concentrations of 1–100 nM, several such forks inhibited the growth of human tumor cell lines bearing both relevant antigens. The same cells were not inhibited by unconjugated component antibodies, and the active conjugates did not inhibit

David B. Ring; Sylvia T. Hsieh-Ma; Tim Shi; John Reeder

1994-01-01

350

Inhibition of Amino Acid Transport in Escherichia coli by Some Beta-Lactam Antibiotics  

PubMed Central

Among 10 antibiotics tested, cephaloridine and cephalothin showed the greatest inhibition of proline active transport. Ethylenediaminetetraacetate pretreatment of the cells did not enhance inhibition by any of these 10 antibiotics. The inhibition of active transport of 10 additional amino acids by cephaloridine and cephalothin was studied. Both antibiotics inhibited transport of three amino acids which, like proline, have transport systems resistant to osmotic shock; neither antibiotic inhibited transport of the remaining amino acids, including three with shock-resistant and four with shock-sensitive systems.

Anderson, Scott V.; Berg, Claire M.

1977-01-01

351

Functional Inhibition of Retinoic Acid Response by Dominant Negative Retinoic Acid Receptor Mutants  

Microsoft Academic Search

The diverse effects of retinoids on the development, growth, and homeostasis of vertebrate organisms are mediated in part by three distinct isoforms of retinoic acid receptors (RARs). These proteins, which are structurally and functionally closely related to thyroid hormone receptors and the oncogene product v-ErbA, regulate patterns of gene expression in target tissues. One approach to study the distinct effects

Klaus Damm; Richard A. Heyman; Kazuhiko Umesono; Ronald M. Evans

1993-01-01

352

Calcium oxalate monohydrate crystallization: citrate inhibition of nucleation and growth steps  

NASA Astrophysics Data System (ADS)

The inhibitory action of citrate on calcium oxalate monohydrate (COM) crystallization has been examined in terms of nucleation and crystal growth kinetic properties. Lag-time data for the appearance of crystals and [ 14C] oxalate incorporation under crystal growth conditions allowed us to investigate the influence of citrate at physiological levels (3.5mM). Moreover, through the use of the EQUIL software, we formulated our solutions based on calculations of solute composition such that free calcium concentrations were the same in the absence and presence of this tricarboxylic acid. The presence of citrate had little effect on the apparent interfacial free energy as determined by nucleation kinetic studies, but total particle production was greater in the absence of citrate; this was evident from electron microscopy and was also indicated by corresponding values of pre-exponential terms of the Gibbs-Thomson equation. Crystal growth rates were lowered in the presence of citrate to 30% of the uninhibited value, and distinctive morphological habit modifications were also observed by scanning electron microscopy. Together, these findings suggest that citrate may influence COM crystallization at several stages, and we present a model for face-specific growth inhibition by citrate acting on the (010) COM crystal face.

Antinozzi, Peter A.; Brown, Charles M.; Purich, Daniel L.

1992-11-01

353

The inhibition of low carbon steel corrosion in hydrochloric acid solutions by succinic acid  

Microsoft Academic Search

The effect of succinic acid (SA) on the corrosion inhibition of a low carbon steel (LCS) electrode has been investigated in aerated non-stirred 1.0M HCl solutions in the pH range (2–8) at 25°C. Weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques were applied to study the metal corrosion behaviour in the absence and presence of different concentrations of

Mohammed A. Amin; Sayed S. Abd El-Rehim; E. E. F. El-Sherbini; Rady S. Bayoumi

2007-01-01

354

Inhibition of Fatty Acid Synthase Attenuates CD44-Associated Signaling and Reduces Metastasis in Colorectal Cancer  

PubMed Central

Fatty Acid Synthase (FASN) and ATP-citrate lyase (ACLY), key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of CD44, a transmembrane protein associated with metastases in several cancers including CRC. In addition, inhibition of lipogenic enzymes and reduced expression of CD44 attenuated the activation of MET, Akt, FAK, and paxillin, which are known to regulate adhesion, migration and invasion. These changes were consistent with an observed decrease in migration and adhesion of CRC cells in functional assays and with re-organization of actin cytoskeleton upon FASN inhibition. Despite the modest effect of FASN inhibition on tumor growth in xenografts, attenuation of lipogenesis completely abolished establishment of hepatic metastasis and formation of secondary metastasis. Together, our findings suggest that targeting de novo lipogenesis may be a potential treatment strategy for advanced CRC.

Zaytseva, Yekaterina Y.; Rychahou, Piotr G.; Gulhati, Pat; Elliott, Victoria A.; Mustain, William C.; O'Connor, Kathleen; Morris, Andrew J.; Sunkara, Manjula; Weiss, Heidi L.; Lee, Eun Y.; Evers, B. Mark

2013-01-01

355

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

PubMed Central

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

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

2013-01-01

356

Caffeic Acid phenethyl ester inhibits epithelial-mesenchymal transition of human pancreatic cancer cells.  

PubMed

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

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

2013-01-01

357

Expansins are involved in cell growth mediated by abscisic acid and indole-3-acetic acid under drought stress in wheat.  

PubMed

Expansin protein is a component of the cell wall generally accepted to be the key regulator of cell wall extension during plant growth. Plant hormones regulate expansin gene expression as well as plant growth during drought stress. However, the relationship between expansin and plant hormone is far from clear. Here, we studied the involvement of expansin in plant cell growth mediated by the hormones indole-3-acetic acid (IAA) and abscisic acid (ABA) under osmotic stress which was induced by polyethylene glycol (PEG)-6000. Wheat coleoptiles from a drought-resistant cultivar HF9703 and a drought-sensitive cultivar 921842 were used to evaluate cell growth and expansin activity. Osmotic stress induced the accumulation of ABA. ABA induced expansin activity mainly by enhancing expansin expression, since ABA induced cell wall basification via decreasing plasma membrane H(+)-ATPase activity, which was unfavorable for expansin activity. Although ABA induced expansin activity and cell wall extension, treatment with exogenous ABA and/or fluridone (FLU, an ABA inhibitor) suggested that ABA was involved in the coleoptile growth inhibition during osmotic stress. IAA application to detached coleoptiles also enhanced coleoptile growth and increased expansin activity, but unlike ABA, IAA-induced expansin activity was mainly due to the decrease of cell wall pH by increasing plasma membrane H(+)-ATPase activity. Compared with drought-sensitive cultivar, the drought-resistant cultivar could maintain greater expansin activity and cell wall extension, which was contributive to its resultant faster growth under water stress. PMID:22076248

Zhao, Mei-rong; Han, Yang-yang; Feng, Ya-nan; Li, Feng; Wang, Wei

2012-04-01

358

Diterpenes from Xylopia langsdorffiana inhibit cell growth and induce differentiation in human leukemia cells.  

PubMed

Two new diterpenes were isolated from stems and leaves of Xylopia langsdorffiana, ent-atisane-7alpha,16alpha-diol (xylodiol) and ent-7alpha-acetoxytrachyloban-18-oic acid (trachylobane), along with the known 8(17),12E,14-labdatrien-18-oic acid (labdane). We investigated their antitumour effects on HL60, U937 and K562 human leukemia cell lines. We found that xylodiol was the most potent diterpene in inhibiting cell proliferation of HL60, U937 and K562 cells, with mean IC50 values of 90, 80 and 50 microM, respectively. Based on the nitroblue tetrazolium (NBT) reduction assay, all the diterpenes were found to induce terminal differentiation in HL60 and K562 cells, with xylodiol being the most effective. NBT reduction was increased by almost 120% after 12 h exposure of HL60 cells to xylodiol at a concentration lower than the IC50 (50 microM). Thus, xylodiol inhibited human leukemia cell growth in vitro partly by inducing cell differentiation, and merits further studies to examine its mechanism of action as a potential antitumoural agent. PMID:19957432

Castello Branco, Marianna V S; Anazetti, Maristella C; Silva, Marcelo S; Tavares, Josean F; Diniz, Margareth F F Melo; Frungillo, Lucas; Haun, Marcela; Melo, Patrícia S

2009-01-01

359

Inhibition of juvenile myelomonocytic leukemia cell growth in vitro by farnesyltransferase inhibitors.  

PubMed

Juvenile myelomonocytic leukemia (JMML) is an early childhood disease for which there is no effective therapy. Therapy with 13-cis retinoic acid or low-dose chemotherapy can induce some responses, but neither mode is curative. Stem cell transplantation can produce lasting remissions but is hampered by high rates of relapse. The pathogenesis of JMML involves deregulated cytokine signal transduction through the Ras signaling pathway, with resultant selective hypersensitivity of JMML cells to granulocyte-macrophage colony-stimulating factor (GM-CSF). A JMML mouse model, achieved through homozygous deletion of the neurofibromatosis gene, confirmed the involvement of deregulated Ras in JMML pathogenesis. With this pathogenetic knowledge, mechanism-based treatments are now being developed and tested. Ras is critically dependent on a prenylation reaction for its signal transduction abilities. Farnesyltransferase inhibitors are compounds that were developed specifically to block the prenylation of Ras. Two of these compounds, L-739,749 and L-744, 832, were tested for their ability to inhibit spontaneous JMML granulocyte-macrophage colony growth. Within a dose range of 1 to 10 micromol/L, each compound demonstrated dose-dependent inhibition of JMML colony growth. An age-matched patient with a different disease and GM-CSF-stimulated normal adult marrow cells also demonstrated dose-dependent inhibitory effects on colony growth, but they were far less sensitive to these compounds than JMML hematopoietic progenitors. Even if the addition of L-739,749 were delayed for 5 days, significant inhibitory effects would still show in JMML cultures. These results demonstrate that a putative Ras-blocking compound can have significant growth inhibitory effects in vitro, perhaps indicating a potential treatment for JMML. (Blood. 2000;95:639-645) PMID:10627474

Emanuel, P D; Snyder, R C; Wiley, T; Gopurala, B; Castleberry, R P

2000-01-15

360

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

SciTech Connect

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

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

2012-01-01

361

Boric acid inhibition of steam generator materials corrosion  

SciTech Connect

In 1974, Westinghouse recommended a change from phosphate water chemistry control for nuclear steam generators to one in which no solids are intentionally added, called all volatile treatment (AVT). The reason for the recommended change in water chemistry control was the occurrence of phosphate thinning of the Alloy 600 heat transfer tubes in some operating plants. Since the change over to AVT, other types of corrosion from impurities in the water have been observed of the materials of construction of nuclear steam generators. Initially, several plants observed denting, which is caused by the corrosion of the carbon steel tube support plates. After 8 yr of usage as a denting inhibitor in nuclear plants, no detrimental effects have been identified as due to boric acid. It is believed that boric acid will inhibit denting-type corrosion and caustic attack of Alloy 600; however, it must be stressed that it is not a substitute for good chemistry practices and all levels and disciplines within the operating plant should recognize the importance of rigorous, long-term chemistry control.

Wootten, M.J.; Wolfe, C.R.; Hermer, R.E.

1985-01-01

362

All-trans-retinoic acid induces cell growth arrest in a human medulloblastoma cell line  

Microsoft Academic Search

Medulloblastomas (MBs) are the most common malignant brain tumors of childhood. Antitumor agents promoting long-term survival\\u000a with limited toxicities are thus far lacking. Preliminary findings suggest that retinoic acid (RA) derivatives (retinoids)\\u000a exert antitumor effects by inhibiting cell proliferation and inducing cell differentiation, apoptosis, and growth arrest,\\u000a and RAs have been specifically shown to induce apoptosis in some MB cells.

Qing Chang; Zhengshan Chen; Jiangfeng You; Michael A. McNutt; Ting Zhang; Zhihui Han; Xiaoyan Zhang; Encong Gong; Jiang Gu

2007-01-01

363

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

Microsoft Academic Search

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

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

2011-01-01

364

Novel Regulation of Fibroblast Growth Factor 2 (FGF2)-mediated Cell Growth by Polysialic Acid*  

PubMed Central

Polysialic acid (polySia) is a unique polysaccharide that modifies neural cell adhesion molecule (NCAM) spatiotemporally. Recently, we demonstrated that polySia functions as a reservoir for several neurotrophic factors and neurotransmitters. Here, we showed the direct interaction between polySia and fibroblast growth factor-2 (FGF2) by native-PAGE, gel filtration, and surface plasmon resonance. The minimum chain length of polySia required for the interaction with FGF2 was 17. Compared with heparan sulfate, a well known glycosaminoglycan capable of forming a complex with FGF2, polySia formed a larger complex with distinct properties in facilitating oligomerization of FGF2, as well as in binding to FGF receptors. In polySia-NCAM-expressing NIH-3T3 cells, which were established by transfecting cells with either of the plasmids for the expression of the polysialyltransferases ST8SiaII/STX and ST8SiaIV/PST that can polysialylate NCAM, FGF2-stimulated cell growth, but not cell survival, was inhibited. Taken together, these results suggest that polySia-NCAM might be involved in the regulation of FGF2-FGF receptor signaling through the direct binding of FGF2 in a manner distinct from heparan sulfate.

Ono, Sayaka; Hane, Masaya; Kitajima, Ken; Sato, Chihiro

2012-01-01

365

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

Microsoft Academic Search

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

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

1995-01-01

366

Inhibition of 5-aminolevulinic acid (ALA) dehydratase by undissociated levulinic acid during ALA extracellular formation by Rhodobacter sphaeroides  

Microsoft Academic Search

The inhibition of ALA dehydratase by levulinic acid during ALA extracellular formation of Rhodobacter sphaeroides correlated\\u000a with the concentration of undissociated form of levulinic acid irrespective of culture pH. The inhibition constant, Ki, of\\u000a intracellular ALA dehydratase by Dixon plots was 2.95 ?M. Undissociated levulinic acid therefore functions as an inhibitor\\u000a of ALA dehydratase.

Ken Sasaki; Masanori Watanabe; Naomichi Nishio

1997-01-01

367

Activation of hypothalamic gamma-aminobutyric Acid receptors resets the pendulum of the growth hormone clock.  

PubMed

Abstract Plasma levels of growth hormone in male rats exhibit an ultradian rhythm having a periodicity of 3 to 4 h, bursts of growth hormone being separated by troughs when growth hormone secretion ceases. To determine if neurons in the vicinity of somatostatin neurons in the preoptic/anterior hypothalamic area participate in the generation of the rhythm, we temporarily inhibited this region with injections of the gamma-aminobutyric acid agonist, muscimol, in unanaesthetized rats previously prepared with a venous catheter and stereotaxically implanted intracerebral guide tubes. The injection resulted in an immediate burst of growth hormone release, followed by a trough period and another growth hormone burst, 3.4 +/- 0.1 h later. The induction of a trough and synchronization of growth hormone bursts was not reproduced by a burst of intravenously injected exogenous growth hormone at least as large as the first burst initiated by muscimol. These findings indicate that, in the short term, the ultradian rhythm is independent of growth hormone feedback and provide the first evidence that structures in the anterior hypothalamus receiving a gamma-aminobutyric acid input are an important component of the neural generator of the ultradian rhythm of growth hormone. PMID:19215359

Willoughby, J O; Kapoor, R

1990-06-01

368

Fatty Acid Synthase Inhibition in Human Breast Cancer Cells Leads to Malonyl-CoA-Induced Inhibition of Fatty Acid Oxidation and Cytotoxicity  

Microsoft Academic Search

Inhibition of fatty acid synthase (FAS) induces apoptosis in human breast cancer cells in vitro and in vivo without toxicity to proliferating normal cells. We have previously shown that FAS inhibition causes a rapid increase in malonyl-CoA levels identifying malonyl-CoA as a potential trigger of apoptosis. In this study we further investigated the role of malonyl-CoA during FAS inhibition. We

Jagan N. Thupari; Michael L. Pinn; Francis P. Kuhajda

2001-01-01

369

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

PubMed Central

BACKGROUND Gastroesophageal reflux is a risk factor for esophageal adenocarcinoma and bile acid and its farnesoid X receptor (FXR) have been implicated in esophageal tumorigenesis. We investigated the role of FXR expression and activity in esophageal cancer initiation and growth. METHODS FXR expression in esophageal adenocarcinoma tissues was assessed by immunohistochemistry. Knockdown of FXR expression in esophageal cancer cells in vitro and in nude mice xenografts was suppressed by FXR shRNA and guggulsterone (a natural FXR inhibitor). Esophageal cancer cells were treated with bile acids to show their effects on growth-promoting genes. RESULTS FXR was expressed in 48 of 59 esophageal adenocarcinoma tissues (81.3%), and this overexpression was associated with higher tumor grade, greater tumor size, and lymph node metastasis, but was inversely associated with RAR-?2 expression. Knockdown of FXR expression suppressed tumor cell growth in vitro and in nude mouse xenografts. Guggulsterone reduced viability of esophageal cancer cells in a time- and dose-dependent manner, whereas this effect was