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Eugenol inhibit 7,12‐dimethylbenz[a]anthracene‐induced genotoxicity in MCF‐7 cells: Bifunctional effects on CYP1 and NAD(P)H:quinone oxidoreductase
Author(s) -
Han Eun Hee,
Hwang Yong Pil,
Jeong Tae Cheon,
Lee Sang Seop,
Shin Jae-Gook,
Jeong Hye Gwang
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.01.044
Subject(s) - dmba , 7,12 dimethylbenz[a]anthracene , chemistry , eugenol , biochemistry , nad+ kinase , genotoxicity , carcinogen , pharmacology , enzyme , biology , toxicity , organic chemistry , carcinogenesis , gene
Typically, chemopreventive agents either inhibit the cytochrome P450s (CYPs) that are essential for the metabolism of carcinogens or induce phase II detoxifying enzymes. This study examined the chemopreventive effect of eugenol on 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced DNA damage in MCF‐7 cells. Eugenol inhibited the formation of the DMBA–DNA adduct in a dose dependent manner. CYP1A1 and CYP1B1 activity, which catalyze the biotransformation of DMBA, were strongly inhibited by eugenol. Eugenol also suppressed the CYP1A induction by DMBA through decreased aryl hydrocarbon receptor activation and subsequent DNA binding. Furthermore, eugenol increased the expression and activity of NAD(P)H:quinone oxidoreductase (QR), a major detoxifying enzyme for DMBA, through NF‐E2 related factor2 binding to antioxidant response element in QR gene. Therefore, eugenol has a potent protective effect against DMBA‐induced genotoxicity, presumably through the suppression of the DMBA activation and the induction of its detoxification. These results suggest that eugenol has potential as a chemopreventive.