Red clover isoflavones biochanin A and formononetin are potent ligands of the human aryl hydrocarbon receptor

J Steroid Biochem Mol Biol. 2008 Jan;108(1-2):171-7. doi: 10.1016/j.jsbmb.2007.10.001. Epub 2007 Oct 22.


Aryl hydrocarbon receptor (AhR) activation affects the cell cycle and drives cells to apoptosis. Thus, selective AhR modulators (SAhRMs) have previously been implicated in cancer therapy and prevention, particularly for hormone-dependent cancers. In the present study, isoflavones a remedy used to ameliorate menopausal complaints were tested for their potential in transactivating AhR in order to investigate the biological function of red clover isoflavones. The results were compared to the transactivation potentials of other flavonoids and plant-derived indole compounds. We found that the isoflavones biochanin A and formononetin were potent AhR agonists in vitro, with EC(50) values of 2.5 x 10(-7) and 1.3 x 10(-7)mol/l, respectively. These isoflavones are 10 times more potent compared to the indole compounds indole-3-carbinol and diindolylmethane, publicised as powerful AhR agonists with EC(50) values of 5.8 x 10(-6) and 1.1 x 10(-6)mol/l, respectively. Because activated AhR crosstalks with estrogen receptor alpha, future risk-benefit assessments of isoflavones should take into consideration their AhR transactivating potential.

Publication types

  • Comparative Study

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Estrogens / pharmacology
  • Genistein / isolation & purification
  • Genistein / pharmacology*
  • Humans
  • Isoflavones / isolation & purification
  • Isoflavones / pharmacology*
  • Ligands*
  • Phytoestrogens / isolation & purification
  • Phytoestrogens / pharmacology
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Saccharomyces cerevisiae
  • Trifolium / chemistry*


  • Estrogens
  • Isoflavones
  • Ligands
  • Phytoestrogens
  • Receptors, Aryl Hydrocarbon
  • formononetin
  • Genistein
  • biochanin A