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 μM 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 (MDRl), 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.