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

Published online by Cambridge University Press:  09 March 2007

Lai See Po
Affiliation:
Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin NT, Hong Kong
Thomas T. Wang
Affiliation:
US Department of Agriculture, Beltsville Human Nutrition Research Center, Phytonutrients Laboratory, Beltsville, MD 20705, USA
Zhen-Yu Chen
Affiliation:
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin NT, Hong Kong
Lai K. Leung*
Affiliation:
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin NT, Hong Kong
*
*Corresponding author: Dr Lai K. Leung, fax +852 2603 7732, [email protected]
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Abstract

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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.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2002

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