Stimulation of microsomal NADPH oxidation by quinone group-containing anticancer chemicals.
Several anticancer chemicals containing a quinone group were found to stimulate the aerobic oxidation of NADPH by liver microsomes. The enzyme responsible for the above reaction was identified as NADPH-cytochrome c reductase (EC 1.6.2.4), one of the microsomal flavoproteins. The fact that a catalytic amount (20 micronM) of these anticancer chemicals was sufficient to oxidize all the NADPH (100 micronM) indicates that they function as electron carries from the flavoprotein to molecular oxygen. As a corollary, Mitomycin-C and Carbazilquinone stimulated oxygen uptake by Ehrlich ascites tumor cells in the presence of glucose that Daunomycin and Adriamycin failed to do so, although the reason for it remains to be elucidated. Carbazilquinone, in contrast to others, also stimulated the microsomal NADH oxidation.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002225:Carbazilquinone / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D008937:Mitomycins / Q000494:pharmacology; D009249:NADP / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011809:Quinones / Q000494:pharmacology*; D051381:Rats
D000970:Antineoplastic Agents; D008937:Mitomycins; D011809:Quinones; D002225:Carbazilquinone; D009249:NADP; D004317:Doxorubicin; D009251:NADPH-Ferrihemoprotein Reductase; D005947:Glucose; D003630:Daunorubicin