Action of curcumin on the cytochrome P450-system catalyzing the activation of aflatoxin B 1

Abstract

Curcumin, in a dose-dependent manner, inhibited the formation of covalent adduct between aflatoxin B 1 and DNA, as catalyzed by microsomes or a reconstituted microsomal monooxygenase system. Its effect on the cytochrome P450-system was investigated in the latter system. The inhibition (50%) of aflatoxin B 1-DNA adduct formation by curcumin in this system could be reversed by increasing the amount of cytochrome P450 but not by that of NADPH-cytochrome P450 reductase. Curcumin inhibited the reductase activity when measured by the reduction of cytochrome C but not when measured by the reduction of dichlorophenolindophenol, an artificial electron acceptor. These results, as well as the reversal of curcumin-induced inhibition of P450 reductase activity by higher amounts of cytochrome C, indicated a strong affinity of curcumin towards cytochromes. This was further substantiated from the observation that curcumin-pretreated cytochrome P450 had reduced ability to catalyze aflatoxin B 1-DNA adduct formation in the reconstituted system. Curcumin, thus, may inhibit chemical carcinogenesis by modulating cytochrome P450 function.