Effects of the flavonoid biochanin A on gene expression in primary human hepatocytes and human intestinal cells.
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.
Moon
Young Jin
YJ
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY 14260, USA.
Zhang
Shuzhong
S
Brazeau
Daniel A
DA
Morris
Marilyn E
ME
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
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