Eugenol inhibit 7,12-dimethylbenz[a]anthracene-induced genotoxicity in MCF-7 cells: Bifunctional effects on CYP1 and NAD(P)H:quinone oxidoreductase

Eun Hee Han; Yong Pil Hwang; Tae Cheon Jeong; Sang Seop Lee; Jae-Gook Shin; Hye Gwang Jeong

doi:10.1016/j.febslet.2007.01.044

Eugenol inhibit 7,12-dimethylbenz[a]anthracene-induced genotoxicity in MCF-7 cells: Bifunctional effects on CYP1 and NAD(P)H:quinone oxidoreductase

FEBS Lett. 2007 Feb 20;581(4):749-56. doi: 10.1016/j.febslet.2007.01.044. Epub 2007 Jan 25.

Authors

Eun Hee Han¹, Yong Pil Hwang, Tae Cheon Jeong, Sang Seop Lee, Jae-Gook Shin, Hye Gwang Jeong

Affiliation

¹ BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Kwangju 501-759, South Korea.

PMID: 17275817
DOI: 10.1016/j.febslet.2007.01.044

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

9,10-Dimethyl-1,2-benzanthracene / analogs & derivatives
9,10-Dimethyl-1,2-benzanthracene / toxicity*
Aryl Hydrocarbon Hydroxylases / genetics
Aryl Hydrocarbon Hydroxylases / metabolism
Cell Line, Tumor
Cytochrome P-450 CYP1A1 / genetics
Cytochrome P-450 CYP1A1 / metabolism*
Cytochrome P-450 CYP1B1
DNA Adducts / drug effects
DNA Damage*
Eugenol / pharmacology*
Gene Expression Regulation, Enzymologic / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Humans
Microsomes / drug effects
Microsomes / enzymology
NAD(P)H Dehydrogenase (Quinone) / metabolism*
NF-E2-Related Factor 2 / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Aryl Hydrocarbon / genetics
Regulatory Sequences, Nucleic Acid / drug effects
Transcriptional Activation / drug effects

Substances

7,12-dimethylbenz(a)anthracene-DNA adduct
DNA Adducts
NF-E2-Related Factor 2
NFE2L2 protein, human
RNA, Messenger
Receptors, Aryl Hydrocarbon
Eugenol
9,10-Dimethyl-1,2-benzanthracene
Aryl Hydrocarbon Hydroxylases
CYP1B1 protein, human
Cytochrome P-450 CYP1A1
Cytochrome P-450 CYP1B1
NAD(P)H Dehydrogenase (Quinone)
NQO1 protein, human