Differential effects of dietary phyto-oestrogens daidzein and equol on human breast cancer MCF-7 cells.
The in vitro effects of two closely related phyto-oestrogens daidzein and equol on the oestrogen receptor positive human breast cancer cells MCF-7 were examined. There is differential metabolism of daidzein in humans, and the conversion of daidzein to equol by intestinal microbes occurs only in 30% of the population. The differential potency of these two compounds is thus of considerable importance since it may be likely that the relative risk of hormone-dependent cancers may be higher in 'non-responders'. In the present study, we compared the ability of both these compounds to induce mRNA expression of the oestrogen-responsive pS2 gene, to compete with oestradiol for binding to the oestrogen receptor (ER) and to affect cellular proliferation. Our studies demonstrate that equol is a 100-fold more potent than daidzein in stimulating an oestrogenic response. Equol was also more effective than daidzein in competing with 3H-oestradiol for binding to the ER. These results suggest that equol has a higher affinity for the ER. Both compounds stimulated the growth of MCF-7 cells in a concentration-dependent manner (10(-8)-10(-5)M). Although equol exhibits oestrogenic activity, exposure of MCF-7 cells to equol simultaneously with oestradiol was effective in reducing pS2 mRNA expression. This was not observed with daidzein. However, long-term exposure of MCF-7 cells to both daidzein and equol resulted in the downregulation of ER mRNA expression.
Sathyamoorthy
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Laboratory of Nutritional and Molecular Regulation, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Wang
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D001943:Breast Neoplasms / Q000378:metabolism*; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D060754:Equol; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D002839:Chromans; D004965:Estrogen Antagonists; D007529:Isoflavones; D008996:Monoamine Oxidase Inhibitors; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen; D060754:Equol; C004742:daidzein