Metabolic Pathway of Dibenzoylmethane, a β-diketone Analogue of Curcumin, by NADPH-dependent Cytochrome P450 Enzymes in Mouse Liver Microsomes
CHUAN-CHUAN LIN1, GUOR-JIEN WEI2, MOU-TUAN HUANG3 AND CHI-TANG HO2*
1. Department of Food Science, China Institute of Technology, Taipei City 115, Taiwan, R.O.C.
2. Department of Food Science, Cook College, Rutgers, the State University of New Jersey, 65 Dudley Road, New Brunswick, NJ 08901-8520, U.S.A.
3. Laboratory for Cancer Research, School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ 08854-8020, U.S.A.
(Received: May 4, 2005; Accepted: July 11, 2005)
ABSTRACT
Dibenzoylmethane (DBM), a curcumin-related β-diketone analogue, has been reported to exhibit a remarkable inhibitory effect on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in Sencar mice. Investigation of the underlying mechanisms of DBM in the prevention of mammary tumorigenesis implied its role as an effector of Phase I enzymatic system. In this report, the metabolic fate of DBM by NADPH-dependent cytochrome P450 enzymes in mouse liver microsomes was demonstrated. Isolation of the major reductive metabolites of DBM (DBMH2), together with several minor metabolites identified by NMR, GC and LC-MS, explained the potential role of DBM as a modulator of the cytochrome P450 reductase that is required for the function of oxidase to metabolize DMBA. These might also contribute to the result of the inhibitory effect of DBM on DMBA-induced mouse mammary tumorigenesis.
Key words: dibenzoylmethane, 7,12-dimethylbenz[a]anthracene, reductive metabolite, mouse liver microsomes, NADPH-dependent cytochrome P450 enzymes, mammary tumorigenesis