Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A structurally diverse group of chemopreventive agents was evaluated using in vitro biomarkers of the carcinogenesis process. With cultured human bronchial epithelial (BEAS-2B) cells, sulfur-containing compounds such as 1.2-dithiole-3-thione and sulforaphane, and phenolic compounds such as caffeic acid phenethyl ester and genistein, showed potent inhibition of benzo(a)pyrene [B(a)P] metabolite-DNA binding. Phenolic compounds also demonstrated strong antioxidant activity. Most of the test compounds did not inhibit 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity with cultured mouse epidermal ME 308 cells, with the exception of sulfur-containing compounds, 1,2-dithiole-3-thione and sulforaphane, and a selenium compound, 1,4-phenylenebis (methylene)selenocyanate. With cultured Hepa 1c1c7 cells, sulforaphane and 1,2-dithiole-3-thione mediated strong induction of quinone reductase, and genistein and ursolic acid were moderate inducers. Chalcone, 1,4-phenylenebis (methylene)selenocyanate and caffeic acid phenethyl ester induced HL-60 cell differentiation. Interestingly, sulforaphane and caffeic acid phenethyl ester inhibited the total metabolism of benzo(a)pyrene with cultured BEAS-2B cells, and the distribution pattern of water-soluble metabolites was altered in comparison with the control groups. These data are suggestive of pleiotropic mechanisms that should prove beneficial when considering the chemopreventive activity of these substances. As a result, of the group of 25 agents tested, four were judged as superior cancer chemopreventive agents: caffeic acid phenethyl ester, 1,2-dithiole-3-thione, genistein, and sulforaphane.
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PMID:Modulation of in vitro biomarkers of the carcinogenic process by chemopreventive agents. 1022 22

Chalcone is a unique template that is associated with several biological activities. In this review, an update of the cytotoxic and chemoprotective activities of chalcones is provided. Cytotoxicity against tumour cell lines may be the result of disruption of the cell cycle, inhibition of angiogenesis, interference with p53-MDM2 interaction, mitochondrial uncoupling or induction of apoptosis. Structural requirements for cytotoxic activity vary according to the mechanisms of action. For anti-mitotic activity, the presence of methoxy substituents, alpha-methylation of the enone moiety and the presence of 2' oxygenated substituents are favourable features. Conformational restraint of the chalcone template generally leads to a decrease in cytotoxic activity. Chemoprotection by chalcones may be a consequence of their antioxidant properties, mediated via inhibition or induction of metabolic enzymes, by an anti-invasive effect or a reduction in nitric oxide production. Hydroxyl and prenyl substituents are associated with antioxidant properties and induction of quinone reductase activities. The thiol reactivity of chalcones is likely to contribute to both cytotoxic and chemoprotective properties of these compounds.
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PMID:Chalcones: an update on cytotoxic and chemoprotective properties. 1572 Feb 56