Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indole-3-carbinol (I3C) was examined for its ability to inhibit aflatoxin B1 (AFB1)-induced hepatocarcinogenesis in male Fischer rats when administered either before or after the carcinogen. After 13 weeks, animals pretreated with I3C (0.5% in the diet) for 2 weeks prior to administration of AFB1 and with continuing treatment during exposure to the carcinogen were protected from development of preneoplastic lesions, as determined by the classical markers gamma-glutamyltranspeptidase (GGT) and glutathione S-transferase (GST) P. In animals receiving AFB1 for 6 weeks before treatment with I3C, there was no obvious protective effect at 13 weeks compared with animals receiving only AFB1. Using cytokeratin 18 expression as a marker, animals fed AFB1 alone had a small number of positive foci at 13 weeks. However, no cytokeratin-positive foci were visible in the majority of livers from either group receiving I3C in combination with AFB1 and after 43 weeks all animals in these groups were protected from liver tumour formation. These results suggest that expression of cytokeratin 18, a later phenotypic change in foci than induction of GST-P and GGT, correlates more closely with tumour outcome in this model. I3C appeared to retard progression of AFB1-induced carcinogenesis at both the initiation and promotion stages. Continuous treatment with I3C for 13 weeks caused significant induction of CYP1A1, 1A2, 3A and 2B1/2, GST Yc2, aflatoxin B1 aldehyde reductase and quinone reductase. Such alteration of the drug metabolizing capacity of the liver by I3C contributes to blocking of initiation, while the observed inhibition of ornithine decarboxylase, a rate limiting enzyme in polyamine biosynthesis, and of tyrosine kinase activity may contribute to the suppressive effect of I3C.
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PMID:Chemoprevention of aflatoxin B1-induced carcinogenesis by indole-3-carbinol in rat liver--predicting the outcome using early biomarkers. 980 66

The effects of the 77 kDa Ju-myo protein, isolated from Drosophila melanogaster, on the development of glutathione S-transferase placental form (GST-P) positive foci in the male F344 rat liver were evaluated using a medium-term bioassay system. No modifying potential was evident in terms of the numbers or areas of GST-P positive foci. Ju-myo protein did not exert any influence on cell proliferation, as reflected by ornithine decarboxylase (ODC) or spermidine/spermine N1-acetyltransferase (SAT) activity and BrdU labeling. These results demonstrated that Ju-myo protein is unlikely to have inhibitory or promoting effects on rat liver carcinogenesis.
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PMID:Lack of inhibitory effects of the Ju-myo protein on development of glutathione S-transferase placental form-positive foci in the male F344 rat liver. 1007 34

Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis was highly purified from the thermophilic bacterium Thermus thermophilus. The enzyme preparation showed a single band on SDS-polyacrylamide gel electrophoresis, a pH optimum of 7.5 and a temperature optimum at 60 degrees C. The native enzyme which is phosphorylated could, upon treatment with alkaline phosphatase, lose all activity. The inactive form could be reversibly activated by nucleotides in the order of NTP>NDP>NMP. When physiological polyamines were added to the purified enzyme in vitro, spermine or spermidine activated ODC by 140 or 40%, respectively, while putrescine caused a small inhibition. The basic amino acids lysine and arginine were competitive inhibitors of ODC, while histidine did not affect the enzyme activity. Among the phosphoamino acids tested, phosphoserine was the most effective activator of purified ODC. Polyamines added at high concentration to the medium resulted in a delay or in a complete inhibition of the growth of T. thermophilus, and in a decrease of the specific activity of ornithine decarboxylase. The decrease of ODC activity resulted from the appearance of a non-competitive inhibitor of ODC, the antizyme (Az). The T. thermophilus antizyme was purified by an ODC-Sepharose affinity column chromatography, as well as by immunoprecipitation using antibodies raised against the E. coli antizyme. The antizyme of E. coli inhibited the ODC of T. thermophilus, and vice versa. The fragment of amino acids 56-292 of the E. coli antizyme, produced as a fusion protein of glutathione S-transferase, did not inhibit the ODC of E. coli or T. thermophilus.
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PMID:Characterization of ornithine decarboxylase and regulation by its antizyme in Thermus thermophilus. 1039 69

A plant polysaccharide, Aloe gel extract, was reported to have an inhibitory effect on benzo[a]pyrene (B[a]P)-DNA adduct formation in vitro and in vivo. Hence, chemopreventive effects of plant polysaccharides [Aloe barbadensis Miller (APS), Lentinus edodes (LPS), Ganoderma lucidum (GPS) and Coriolus versicolor (CPS)] were compared using in vitro short-term screening methods associated with both initiation and promotion processes in carcinogenesis. In B[a]P-DNA adduct formation, APS (180 micrograms/ml) was the most effective in inhibition of B[a]P binding to DNA in mouse liver cells. Oxidative DNA damage (by 8-hydroxydeoxyguanosine) was significantly decreased by APS (180 micrograms/ml) and CPS (180 micrograms/ml). In induction of glutathione S-transferase activity, GPS was found to be the most effective among plant polysaccharides. In screening anti-tumor promoting effects, APS (180 micrograms/ml) significantly inhibited phorbol myristic acetate (PMA)-induced ornithine decarboxylase activity in Balb/3T3 cells. In addition, APS significantly inhibited PMA-induced tyrosine kinase activity in human leukemic cells. APS and CPS significantly inhibited superoxide anion formation. These results suggest that some plant polysaccharides produced both anti-genotoxic and anti-tumor promoting activities in in vitro models and, therefore, might be considered as potential agents for cancer chemoprevention.
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PMID:In vitro chemopreventive effects of plant polysaccharides (Aloe barbadensis miller, Lentinus edodes, Ganoderma lucidum and Coriolus versicolor). 1042 20

The effects of Asakusa-nori, Porphyra tenera (PT), a popular edible seaweed in Japan, on the development of putative preneoplastic lesions, glutathione S-transferase placental form (GST-P)-positive foci, in the male F344 rat liver were examined using a medium-term bioassay system. PT significantly decreased both the number and area of GST-P-positive foci in rat livers initiated with diethylnitrosamine (DEN). To investigate possible mechanisms of inhibition, effects of PT on 5-bromo-2'-deoxyuridine (BrdU) labeling in GST-P-positive foci and the surrounding area of hepatocytes were studied. The ratio of the GST-P-positive foci to surrounding tissue labeling indices was decreased in the PT-treated group as compared with the DEN alone group. Ornithine decarboxylase activity in the liver was slightly increased and spermidine/spermine N'-acetyltransferase activity was slightly decreased in the PT-treated animals. These results suggest that PT possesses chemopreventive effects against DEN-induced hepatocarcinogenesis.
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PMID:Inhibition of liver glutathione S-transferase placental form-positive foci development in the rat hepatocarcinogenesis by Porphyra tenera (Asakusa-nori). 1045 64

In the mouse study, topical application of green tea polyphenols (GTP) significantly inhibited TPA-induced increasing of epidermal ornithine decarboxylase (ODC) and increased the activities of several antioxidant enzymes (CAT, GR and GST). In another in vitro study, when GTP was incubated with TPA and mice polymorphonuclear leukocytes (PMNs), TPA induced hydrogen peroxide formation was markedly suppressed with a dose-dependent relationship. The results suggest that the antioxidative effect of GTP may play an important role in inhibiting tumor promotion.
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PMID:[The antioxidative mechanisms of tea polyphenols in inhibiting tumor promotion by TPA]. 1068 39

The modifying effects of dietary feeding of bovine lactoferrin (bLF) on tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR), polyamine content and ornithine decarboxylase (ODC) activity in the tongue were also examined for mechanistic analysis of possible modifying effects of bLF on carcinogenesis. At 7 weeks of age, all animals except those treated with bLF alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 7 days before 4-NQO exposure, experimental groups were fed experimental diets containing bLF (0.2% and 2%) for 10 weeks ("initiation feeding"). Starting 1 week after the cessation of exposure to 4-NQO, the other experimental groups given 4-NQO and a basal diet were fed the experimental diets for 22 weeks ("postinitiation feeding"). At week 32, the incidence and multiplicity of tongue neoplasms in the "initiation feeding" groups of 0.2% and 2% bLF and the "post-initiation feeding" group of 0.2% bLF were lower than those of the 4-NQO alone group, but without statistical significance. However, "post-initiation feeding" of 2% bLF caused a significant reduction in the incidence (20% vs. 55%, P=0.02418) and multiplicity (0.25+/-0.54 vs. 0.70+/-0.71, P<0.05) of tongue squamous cell carcinoma (by 64%, P=0.02418). bLF treatment elevated liver and tongue GST activities and liver QR activity. The "post-initiation feeding" with 2% bLF significantly decreased QR activity, proliferating cell nulcear antigen-positive index and ODC activity in the tongue. In addition, feeding with bLF decreased tongue polyamine content. These results suggest that bLF, when given at the 2% dose level during the post-initiation phase, exerts chemopreventive action against tongue tumorigenesis through modification of cell proliferation activity and/or the activities of detoxifying enzymes.
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PMID:Chemopreventive effect of bovine lactoferrin on 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. 1074 41

The effects of S-methylcysteine (SMC) and cysteine on the promotion stages of rodent hepatocarcinogenesis in a medium-term bioassay previously developed by Ito were examined. Initiation was induced by a single dose of diethylnitrosamine (DEN), followed by dietary administration of the promoter sodium phenobarbital (NaPB) 2 weeks later, for 6 weeks. Partial hepatectomy was conducted on all the animals at week 3. Inhibitory potential was evaluated by analyzing two markers of carcinogenesis, namely numbers of glutathione S-transferase placental form (GST-P)-positive foci, and proliferating cell nuclear antigen (PCNA). In addition, the level of ornithine decarboxylase (ODC), one of the rate-limiting enzymes of polyamine metabolism induced by promoters, was analyzed. SMC and cysteine induced significant reduction in the areas of GST-P-positive foci. A significant reduction in the PCNA index was observed in the entire liver as well as in GST-P-positive areas. SMC also induced down-regulation of the ODC enzyme activity. Thus, SMC and cysteine were found to inhibit the promotion stage of DEN-induced hepatocarcinogenesis. No cocarcinogenic effects were evident on administration of either of these chemicals with NaPB.
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PMID:Inhibitory effects of S-methylcysteine and cysteine on the promoting potential of sodium phenobarbital on rat liver carcinogenesis. 1096 17

The modulating effect of spearmint (Mentha spicata) on benzoyl peroxide-induced responses of tumor promotion in murine skin was investigated. Benzoyl peroxide (BPO) is an effective cutaneous tumor promoter acting through the generation of oxidative stress, induction of ornithine decarboxylase activity and by enhancing DNA synthesis. BPO treatment (20 mg/animal) increased cutaneous microsomal lipid peroxidation and hydrogen peroxide generation. The activity of cutaneous antioxidant enzymes, namely catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, was decreased and the level of cutaneous glutathione was depleted. BPO treatment also induced the ornithine decarboxylase activity and enhanced the [3H]thymidine uptake in DNA synthesis in murine skin. Prophylactic treatment of mice with spearmint extract (10, 15 and 20 mg/kg) 1 hr before BPO treatment resulted in the diminution of BPO-mediated damage. The susceptibility of cutaneous microsomal membrane to lipid peroxidation and hydrogen peroxide generation was significantly reduced (P < 0.05 ). In addition, depleted levels of glutathione, inhibited activity of glutathione dependent and antioxidant enzymes were recovered to a significant level (P < 0.01, P < 0.05 and P < 0.01, respectively). Similarly, the elevated ornithine decarboxylase activity and enhanced thymidine uptake in DNA synthesis was inhibited significantly (P < 0.05 ) in a dose-dependent manner. The protective effect of spearmint was dose dependent in all parameters. The result suggests that spearmint is an effective chemopreventive agent that may suppress BPO-induced cutaneous oxidative stress, toxicity and hyperproliferative effects in the skin of mice.
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PMID:Attenuation of benzoyl peroxide-mediated cutaneous oxidative stress and hyperproliferative response by the prophylactic treatment of mice with spearmint (Mentha spicata). 1103 27

The chemopreventive effects of five water-soluble organosulfur compounds, S-methylcysteine (SMC) and four analogs, were examined on the promotion stage of diethylnitrosamine hepatocarcinogenesis in male F344 rats, using the medium-term bioassay (Ito test), which is based on the two-step model of hepatocarcinogenesis. In addition, we investigated the modifying effects of SMC and cysteine on the initiation stage of rat hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas of a putative neoplastic lesion, glutathione S-transferase placental form (GST-P)--positive hepatocellular foci. SMC and cysteine significantly decreased the number and area of GST-P--positive foci when given in the promotion stage of the Ito test. When given during the initiation stage, these two organosulfur compounds also significantly inhibited focus formation. Liver ornithine decarboxylase activity after two thirds partial hepatectomy and the proportion of hepatocytes positive for proliferating cell nuclear antigen significantly decreased the number of aberrant crypt foci in the colon in a multiorgan carcinogenesis bioassay of rats. These results support SMC and cysteine as chemopreventive agents for hepatocarcinogenesis and colon carcinogenesis. Their intake may be of importance for cancer.
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PMID:Suppression of chemical carcinogenesis by water-soluble organosulfur compounds. 1123 14


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