Effects of the flavonoid biochanin A on gene expression in primary human hepatocytes and human intestinal cells

Mol Nutr Food Res. 2007 Mar;51(3):317-23. doi: 10.1002/mnfr.200600156.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Adenocarcinoma
  • Anticarcinogenic Agents / pharmacology*
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Arylsulfotransferase / genetics
  • Cell Line, Tumor
  • Colonic Neoplasms
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P450 Family 2
  • Enterocytes / metabolism*
  • Gene Expression / drug effects*
  • Genistein / pharmacology*
  • Hepatocytes / metabolism*
  • Humans
  • Mixed Function Oxygenases / genetics
  • Oxidoreductases, N-Demethylating / genetics
  • Thromboxane-A Synthase / genetics
  • Up-Regulation / drug effects

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anticarcinogenic Agents
  • Cytochrome P-450 Enzyme System
  • Genistein
  • Mixed Function Oxygenases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • CYP2F1 protein, human
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 CYP2B6
  • Cytochrome P450 Family 2
  • Oxidoreductases, N-Demethylating
  • Arylsulfotransferase
  • SULT1A2 protein, human
  • Thromboxane-A Synthase
  • biochanin A