title: Baicalein inhibits DMBA-DNA adduct formation by modulating CYP1A1 and CYP1B1 activities.
abstract: Flavonoids are phenolic compounds isolated from plants, and several of them like genistein and quercetin, have been documented to be effective in preventing cancer. Baicalein, a flavonoid extracted from the root of Scutellaria species, is widely used as a health supplement and herbal medicine in Asian countries. In this study, the chemopreventive effect of baicalein on 7,12-dimethylbenz[a]anthracene (DMBA)-induced DNA damage was evaluated in an established cell culture model. In a preliminary screening, baicalein was identified to be a strong inhibitor to EROD activities induced by DMBA in MCF-7 cells. Subsequent enzyme kinetic analysis revealed that baicalein was a competitive inhibitor to EROD, and CYP1A1 and CYP1B1 gene expressions were also determined. Baicalein could reduce the CYP1A1/1B1 mRNA expressions induced by DMBA, and the mRNA abundance of CYP1A1 appeared to be more responsive than that of CYP1B1. A XRE-luciferase gene reporter assay indicated that AhR transactivation was suppressed. Since CYP1A1/1B1 were responsible for the biotransformation of polycyclic aromatic hydrocarbons, baicalein also demonstrated its ability to reduce DMBA-DNA adduct formation in MCF-7 cells. This study suggested that the natural occurring baicalein could be an agent preventing carcinogen-DNA adduct formation.
authors.affiliation: Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT.
authors.forename: Ho Yee
authors.initials: HY
authors.lastname: Chan
authors.forename: Zhen-yu
authors.initials: ZY
authors.lastname: Chen
authors.forename: David S C
authors.initials: DS
authors.lastname: Tsang
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1; D018736:DNA Adducts / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D014407:Tumor Cells, Cultured
chemical_list: C059444:7,12-dimethylbenz(a)anthracene-DNA adduct; D018736:DNA Adducts; D044950:Flavanones; D005419:Flavonoids; C006680:baicalein; D015127:9,10-Dimethyl-1,2-benzanthracene; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1