Over-expression of DT-diaphorase in transfected NIH 3T3 cells does not lead to increased anticancer quinone drug sensitivity: a questionable role for the enzyme as a target for bioreductively activated anticancer drugs.
Murine NIH 3T3 cells were stably transfected with human NQO1 (DT-diaphorase) cDNA and clonal cell lines with up to 15-fold elevated DT-diaphorase activity were obtained. These cell lines showed no significant increase in cell growth inhibition by the quinone anticancer drugs mitomycin C, diaziquone and menadione, when compared to vector alone transfected control cells. There was a small increase in sensitivity to doxorubicin. The relative increase in DT-diaphorase activity in the transfected cells compared to the control cell lines is similar to the increase of DT-diaphorase activity found in some human tumors compared to their paired normal tissue. The results of this study, and other evidence, suggests that DT-diaphorase may not, as suggested by others, be a clinically useful target for the bioreductive activation of anticancer drugs.
Powis
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Arizona Cancer Center, Arizona Health Sciences Center, University of Arizona, Tucson 85724, USA.
Gasdaska
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PY
Gallegos
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A
Sherrill
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K
Goodman
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D
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001388:Aziridines / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000187:drug effects; D014162:Transfection; D014812:Vitamin K / Q000494:pharmacology
D000970:Antineoplastic Agents; D001388:Aziridines; D016227:Benzoquinones; D014812:Vitamin K; D016685:Mitomycin; D004317:Doxorubicin; D016660:NAD(P)H Dehydrogenase (Quinone); C029108:diaziquone