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)

To study the role of DT-diaphorase in menadione-mediated cytotoxicity, menadione-resistant cells were selected from P19 cells by stepwise increasing concentrations of menadione from 10 to 60, 120 or 300 microM without mutagenic pretreatment. Three isolated clones, K60, K120 and K300, were maintained in media containing 60, 120 or 300 microM menadione, respectively. The resistance of these cells to menadione, in order, was: K300 > K120 > K60 > P19 cells. K300 cells were the most resistant. Acquisition of resistance was associated with elevation in DT-diaphorase activity. Pretreatment of the resistant cells with 30 microM dicumarol at 37 degrees C for 30 min sensitized the resistant cells to menadione. When the resistant cells were maintained in the absence of menadione for 28 days, the resistance of K60 and K120 cells was lost. The lower degree of resistance was accompanied by a decrease in DT-diaphorase activity in the revertant cells. However, the resistance and the activity of DT-diaphorase in K300 cells were quite stable in the same period. These results support strongly that DT-diaphorase protects against menadione-induced oxidative stress.
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PMID:DT-diaphorase protects against menadione-induced oxidative stress. 1061 91

We investigated the role of glutathione (GSH) and antioxidant enzymes in menadione-resistance by using K300 cells (menadione-resistant cells) and parental P19 cells (menadione-sensitive cells). We found that acquisition of resistance was associated with elevations in glutathione content and DT-diaphorase activity. The activity of glutathione S-transferase (GST) was significantly decreased, while the activities of glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase in K300 cells were maintained at the same levels as compared to the parental P19 cells. Using reactive oxygen species (ROS)-sensitive fluorescence dye 2,7- dichlorodihydrofluorescein diacetate (DCFH/DA), we demonstrated that K300 cells are characterized by reduced cellular ROS as compared to the parental P19 cells during menadione's action. Menadione depleted glutathione to a small extent in the K300 cells, but a rapid depletion was observed in P19 cells. Pretreatment of K300 cells with dicumarol, a DT-diaphorase inhibitor, or buthionine sulfoximine (BSO), an inhibitor of gamma-glutamyl cysteine synthase, sensitized the cells to menadione. BSO treatment was less effective than dicumarol treatment in reversing menadione resistance in K300 cells. These results strongly support the belief that DT-diaphorase plays a central role in protecting cells against menadione-induced oxidative stress by decreasing the ROS formation.
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PMID:The roles of glutathione and antioxidant enzymes in menadione-induced oxidative stress. 1111 72

Basic research and clinical chemoprevention trials support the protective role of selenium in cancer prevention but the mechanisms based on the molecular level remain to be fully defined. This mini-review focuses only on the elucidation of the molecular mechanisms of cancer prevention by selenium using the genomics approach; target organs discussed here are breast, prostate, colon and lung. The results described here support the utility of microarray technology in delineating the molecular mechanisms of cancer prevention by selenium. These results are based on studies employing human and rodent cell lines and tissues from animal models ranging from normal to frank cancer. The dose and the form of selenium are determining factors in cancer chemoprevention. The results of the microarray analysis reviewed here indicate that selenium, independent of its form and the target organ examined, alters several genes in a manner that can account for cancer prevention. Selenium can up regulate genes related to phase II detoxification enzymes, certain selenium-binding proteins and select apoptotic genes, while down regulating those related to phase I activating enzymes and cell proliferation. Independent of tissue type, selenium arrests cells in G1 phase of cell cycle, inhibits CYCLIN A, CYCLIN D1, CDC25A, CDK4, PCNA and E2F gene expressions while induces the expressions of P19, P21, P53, GST, SOD, NQO1, GADD153 and certain CASPASES. In addition to those described above, genes such as OPN, which is mainly involved in metastasis and recently reported to be down regulated by selenium, should be considered as potential molecular marker in clinical chemoprevention trials. Collectively, literature data indicate that some of these genes that were altered by selenium are also involved in the development of human cancers described in this review. It appears that androgen receptor status may influence the effect of selenium on gene expression profile in prostate cancer; whether estrogen receptor may influence the effect of selenium on gene expression in breast cancer requires further studies. Knowledge from gene array data in combination with proteomics approaches, using homogenous population of cell types with the aid of laser capture microdissection, may provide an individualized dimension of information on cancer risk and potential targets for its prevention. The molecular (genetic) biomarkers presented in this review will provide the foundation for future studies of the chemopreventive properties of structurally varied selenium compounds.
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PMID:Molecular chemoprevention by selenium: a genomic approach. 1609 79