Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Effect of Biochanin A on the Aryl Hydrocarbon Receptor and Cytochrome P450 1A1 in MCF-7 Human Breast Carcinoma Cells

  • Han, Eun-Hee (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University) ;
  • Kim, Ji-Young (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University) ;
  • Jeong, Hye-Gwang (Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University)
  • Published : 2006.07.01
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Abstract

Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. This study examined the action of biochanin A with the carcinogen activation pathway that is mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. A concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA-inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A treatment alone activated the DNA-binding capacity of the AhR for the dioxin-response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA-inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. These results suggest that biochanin A may thus be a natural ligand to bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of the AhR pathway.

Keywords

References

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