Volume 88, Issue 5, November (2002), pp. 463-469 © The Author 2002
doi:10.1079/BJN2002693

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Genistein-induced apoptosis in MCF-7 cells involves changes in Bak and Bcl-x without evidence of anti-oestrogenic effects

Lai See Po², Thomas T. Wang³, Zhen-Yu Chen¹, Lai K. Leung^1,2
1Food and Nutritional Sciences Programme and ²Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong ³US Department of Agriculture, Beltsville Human Nutrition Research Center, Phytonutrients Laboratory, Beltsville, MD 20705, USA

 (Received 23 October 2001–Revised 7 June 2002–Accepted 18 June 2002)

Abstract

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 μM for the binding to OR-α. In these experiments, genistein concentration as high as 50 μM 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 μM-genistein by Western analysis. The combined effect of these two proteins could be important in the apoptotic process. Since plasma genistein >50 μM 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.

Keywords:
Genistein: Oestrogen receptor: Anti-oestrogen: Cell death