British Journal of Nutrition

Full Papers

The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and expression

Yun Wanga1, Wai Man Ghoa1, Franky L. Chana2, Shiuan Chena3 and Lai K. Leunga1a4 c1

a1 Department of Biochemistry, The Chinese University of Hong Kong, Shatin NT, Hong Kong

a2 Department of Anatomy, The Chinese University of Hong Kong, Shatin NT, Hong Kong

a3 Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA

a4 Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin NT, Hong Kong

Abstract

Biochanin A is an isoflavone isolated from red clover (Trifolium pratense), and is a commercially available nutraceutical for women suffering from postmenopausal symptoms. Isoflavones resemble the structure of oestrogen, and display agonistic and antagonistic interactions with the oestrogen receptor. Overexposure of oestrogen is a major contributing factor in the development of breast cancer, and cytochrome P450 (CYP) 19 enzyme, or aromatase, catalyses the reaction converting androgen to oestrogen. In the present study the effect of biochanin A on the gene regulation and enzyme activity of aromatase was investigated. By assaying MCF-7 cells stably transfected with CYP19, biochanin A inhibited aromatase activity and hampered cell growth attributing to the enzyme activity. In addition, 25 μm-biochanin A significantly reduced CYP19 mRNA abundance in the oestrogen receptor-negative breast cancer cells SK-BR-3. The transcriptional control of the CYP19 gene is exon-specific, and promoter regions I.3 and II have been shown to be responsible for CYP19 expression in SK-BR-3 cells. Luciferase reporter gene assays also revealed that biochanin A could repress the transcriptional control dictated by the promoter regulation. Interestingly, genistein did not inhibit aromatase but it might down regulate promoter I.3 and II transactivation. Since genistein is a major metabolite of biochanin A, it might contribute to biochanin A's suppressive effect on CYP19 expression. The present study illustrated that biochanin A inhibited CYP19 activity and gene expression.

(Received February 08 2007)

(Revised June 22 2007)

(Accepted June 25 2007)

Correspondence:

c1 Corresponding author: Dr Lai K. Leung, fax +852 26037732, email laikleung@cuhk.edu.hk

Footnotes

Abbreviations: CYP, cytochrome P450; IC50, 50 % inhibitory concentration.