title: Effect of biochanin A on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells.
abstract: Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. This study examined the action of biochanin A with the carcinogen activation pathway that is mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. A concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA-inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A treatment alone activated the DNA-binding capacity of the AhR for the dioxin-response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA-inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. These results suggest that biochanin A may thus be a natural ligand to bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of the AhR pathway.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Kwangju, Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Han
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019833:Genistein / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010078:Oxazines / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D018736:DNA Adducts; D010078:Oxazines; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D015127:9,10-Dimethyl-1,2-benzanthracene; C007649:ethoxyresorufin; D004247:DNA; D019833:Genistein; D019363:Cytochrome P-450 CYP1A1; C004541:biochanin A