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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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Adenocarcinoma
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Anticarcinogenic Agents / pharmacology*
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Aryl Hydrocarbon Hydroxylases / genetics
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Arylsulfotransferase / genetics
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Cell Line, Tumor
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Colonic Neoplasms
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Cytochrome P-450 CYP2A6
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Cytochrome P-450 CYP2B6
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Cytochrome P-450 CYP2C9
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Cytochrome P-450 Enzyme System / genetics
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Cytochrome P450 Family 2
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Enterocytes / metabolism*
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Gene Expression / drug effects*
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Genistein / pharmacology*
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Hepatocytes / metabolism*
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Humans
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Mixed Function Oxygenases / genetics
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Oxidoreductases, N-Demethylating / genetics
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Thromboxane-A Synthase / genetics
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Up-Regulation / drug effects
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Anticarcinogenic Agents
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Cytochrome P-450 Enzyme System
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Genistein
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Mixed Function Oxygenases
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CYP2C9 protein, human
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Cytochrome P-450 CYP2C9
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Aryl Hydrocarbon Hydroxylases
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CYP2B6 protein, human
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CYP2F1 protein, human
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Cytochrome P-450 CYP2A6
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Cytochrome P-450 CYP2B6
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Cytochrome P450 Family 2
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Oxidoreductases, N-Demethylating
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Arylsulfotransferase
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SULT1A2 protein, human
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Thromboxane-A Synthase
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biochanin A