Author:
Wang Yun,Man Gho Wai,Chan Franky L.,Chen Shiuan,Leung Lai K.
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 withCYP19, 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 theCYP19gene is exon-specific, and promoter regions I.3 and II have been shown to be responsible forCYP19expression 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.
Publisher
Cambridge University Press (CUP)
Subject
Nutrition and Dietetics,Medicine (miscellaneous)
Reference47 articles.
1. Pharmacokinetics and bioavailability of the isoflavone biochanin A in rats
2. Increased UDP-glucuronosyltransferase activity and decreased prostate specific antigen production by biochanin A in prostate cancer cells;Sun;Cancer Res,1998
3. Chemoprevention ofN-Nitroso-N-methylurea-induced Rat Mammary Carcinogenesis by Soy Foods or Biochanin A
4. Induction of aromatase (CYP19) expression in breast cancer cells through a nongenomic action of estrogen receptor α;Kinoshita;Cancer Res,2003
5. Chalcones are potent inhibitors of aromatase and 17β-hydroxysteroid dehydrogenase activities
Cited by
74 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献