Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Differential effects of dietary phyto-oestrogens daidzein and equol on human breast cancer MCF-7 cells. 961 86

Genistein and daidzein are the main isoflavones in legumes. Equol is an intestinal bacterial metabolite of daidzein. In this study, we evaluated the estrogenic potential of daidzein and synthetic (+/-)-equol to stimulate growth of estrogen-dependent breast cancer (MCF-7) in vitro and in vivo. We hypothesize that estrogenic effects of daidzein and (+/-)-equol could modulate the growth of MCF-7 cells both in vitro and also once implanted into ovariectomized athymic mice. At concentrations between 0.001 and 50 microM, daidzein and (+/-)-equol stimulated the growth of MCF-7 cells with maximal stimulation at 1 muM in vitro. To evaluate their effects on the growth of MCF-7 cells implanted in ovariectomized athymic mice, two dietary dose-response studies [daidzein (125, 250, 500 and 1000 p.p.m.) and (+/-)-equol (250, 500 and 1000 p.p.m.)] were conducted. Tumor size and body weight were monitored weekly during the study. At completion of the study, we analyzed cellular proliferation of tumors using immunohistochemical staining (ki-67), pS2 expression in tumors using a real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and total daidzein and (+/-)-equol levels in plasma using liquid chromatography-electrospray tandem mass spectrometry (LC-ES/MS/MS). Dietary daidzein had a slight but significant stimulatory effect on MCF-7 tumor growth in mice. No significant induction of pS2 mRNA (an estrogen-responsive marker) in tumors by dietary daidzein was observed. Total plasma daidzein concentrations in plasma were between 0.25 and 1.52 microM. Dietary equol treatment (for 37 weeks) did not stimulate MCF-7 tumor growth. There were no statistical differences in tumor size, proliferation and pS2 expression among any treatment groups. Total equol concentrations in plasma were 2.10-3.21 microM. In conclusion, daidzein and (+/-)-equol have proliferative effects on MCF-7 cell growth in vitro within the concentration range tested. Dietary daidzein had a slight but significant stimulatory effect on tumor growth, whereas (+/-)-equol did not stimulate the growth of estrogen-dependent breast tumor growth in athymic mice, increase the cell proliferation in tumors, or induce an estrogen-responsive pS2 expression. Total daidzein or (+/-)-equol plasma levels in mice fed the isoflavones were in the range that stimulated MCF-7 cell growth in vitro. These results suggest that pharmacokinetic and/or metabolic factors attenuate the estrogenic effects of daidzein and equol in vivo.
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PMID:Effects of dietary daidzein and its metabolite, equol, at physiological concentrations on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice. 1639 73