title: Effects of the flavonoid biochanin A on gene expression in primary human hepatocytes and human intestinal cells.
abstract: Biochanin A (BCA), a phytoestrogen present in plant food and herbal products, has been reported to have cancer-preventive effects that may be mediated, in part, through effects on carcinogen metabolism. Our objective was to examine the effect of BCA on gene expression for drug-metabolizing enzymes and transporters in human hepatocytes. Cells were exposed to 20 muM of BCA for 5 days. Gene expression was assessed by a 96-gene human drug metabolism enzyme microarray. There were seven genes that were significantly up-regulated, namely cytochrome P-450 (CYP) 2A6, CYP2B6, CYP2C9, CYP2F1, multidrug resistance gene (MDR1), thromboxane A synthase 1 (TBXAS1), and SULT1A2 (sulfotransferase). Up-regulation of MDR1, which encodes for P-glycoprotein, was confirmed using real-time RT-PCR and Western analysis in hepatocytes as well as in human colon adenocarcinoma cell line (LS-180) and the induction was dose-dependent. BCA treatment up-regulated genes mainly in the CYP2 family. This induction can influence the metabolism of xenobiotics, producing effects of pharmacological and toxicological importance.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY 14260, USA.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Moon
authors.forename: Shuzhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Brazeau
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Morris
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000230:Adenocarcinoma; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D015239:Arylsulfotransferase / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D020895:Enterocytes / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D013930:Thromboxane-A Synthase / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016588:Anticarcinogenic Agents; D003577:Cytochrome P-450 Enzyme System; D019833:Genistein; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; C110332:CYP2F1 protein, human; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; D000072467:Cytochrome P450 Family 2; D010089:Oxidoreductases, N-Demethylating; D015239:Arylsulfotransferase; C513290:SULT1A2 protein, human; D013930:Thromboxane-A Synthase; C004541:biochanin A