Cytochrome P450 reductase, antioxidant enzymes and cellular resistance to doxorubicin

Our data suggest that DOX resistance in P388/R-84 cells may result, at least in part, from reduced free radical formation by both suppression of flavin reductase(s) and overexpression of certain antioxidant enzymes such as GSH peroxidase and catalase. In addition, our results, in conjunction with other studies, indicate that flavin reductase(s) and antioxidant enzymes are differentially altered in cancer cells with acquired or de novo resistance to DOX. Further studies are needed, however, to elucidate the mechanism(s) by which the gene expression of these enzymes is regulated in drug-sensitive and -resistant cells.