Quinone-induced apoptosis in human colon adenocarcinoma cells via DT-diaphorase mediated bioactivation.
DT-diaphorase (DTD) activity has been related to bioactivation and cytotoxicity of antitumor quinones. A pair of human colon adenocarcinoma cell lines, HT29 and BE, were used in this study to examine the role of DTD in antitumor quinone induced apoptosis. HT29 cells have elevated levels of DTD whereas BE cells lack functional DTD due to a point mutation which results in a complete lack of DTD activity. MeDZQ, a quinone that is efficiently bioactivated by DTD, induced apoptosis both in HT29 and BE cells, but with a much higher incidence in HT29, as assessed by morphological criteria and the formation of oligonucleosomal fragments of DNA. Two other quinone compounds which are also substrates for DTD, i.e. streptonigrin and mitomycin C, also preferentially induced apoptosis in HT29 cells, which could be inhibited by dicoumarol. Our data suggest that bioreductive activation of antitumor quinones by DTD results in induction of apoptosis in human colon carcinoma cells.
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School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
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D000230:Adenocarcinoma / Q000473:pathology*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001388:Aziridines / Q000378:metabolism / Q000494:pharmacology; D016227:Benzoquinones / Q000378:metabolism / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology*; D004587:Electrophoresis, Agar Gel; D006801:Humans; D016685:Mitomycin / Q000378:metabolism / Q000494:pharmacology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D013308:Streptonigrin / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001388:Aziridines; D016227:Benzoquinones; C073715:2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone; D013308:Streptonigrin; D016685:Mitomycin; D009247:NADH, NADPH Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone)