Action of curcumin on the cytochrome P450-system catalyzing the activation of aflatoxin B1.
Curcumin, in a dose-dependent manner, inhibited the formation of covalent adduct between aflatoxin B1 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 B1-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 B1-DNA adduct formation in the reconstituted system. Curcumin, thus, may inhibit chemical carcinogenesis by modulating cytochrome P450 function.
Firozi
P F
PF
Radiation Biology and Biochemistry Division, Bhabba Atomic Research Centre, Bombay, India.
Aboobaker
V S
VS
Bhattacharya
R K
RK
D016604:Aflatoxin B1 / Q000378:metabolism*; D000818:Animals; D003474:Curcumin; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D003574:Cytochrome c Group; D018736:DNA Adducts; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D009251:NADPH-Ferrihemoprotein Reductase; D003474:Curcumin