Genistein-induced apoptosis in MCF-7 cells involves changes in Bak and Bcl-x without evidence of anti-oestrogenic effects
2002
Po, L.S. | Wang, T.T. | Chen, Z.Y. | Leung, L.K.
South-east Asian women have a lower rate of breast cancer compared with their counterparts in western countries and the difference in soyabean consumption has been claimed to be a major contributing factor. Genistein is the most studied phytochemical in the soyabean. An anti-oestrogenic effect is believed to play a crucial part in its chemopreventive mechanism. In the present study, we expressed oestrogen receptor (OR) in an OR-negative cell line, HepG2, to investigate the pro- and anti-oestrogenic effect of genistein on the OR transcriptional activity. Genistein by itself had an estimated concentration that induced 50% of the maximum response (EC50) of 2.5 micromolar for the binding to OR-alpha. In these experiments, genistein concentration as high as 50 micromolar could not reduce the oestrogen response element-driven luciferase activities initiated by oestradiol. Instead, genistein potentiated the OR transactivational activity while cell death was detected. On the other hand, an increased Bak and a reduced Bcl-x(L) was observed at 50 micromolar-genistein by Western analysis. The combined effect of these two proteins could be important in the apoptotic process. Since plasma genistein > 50 micromolar has never been documented following consuming of soyabean or soyabean products, the present study does not support the notion that dietary soyabean exerts its chemopreventive effect through antagonizing OR.
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