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Title: GENISTEIN-INDUCED APOPTOSIS IN MCF-7 CELLS INVOLVES CHANGES IN BAK AND BEL-X WITHOUT EVIDENCE OF ANTI-OESTROGENIC EFFECTS

Author
item SEE PO, LAI - UNIV HONG KONG
item Wang, Thomas - Tom
item CHEN, ZHEN-YU - UNIV HONG KONG
item LEUNG, LAI - UNIV HONG KONG

Submitted to: British Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/18/2002
Publication Date: N/A
Citation: N/A

Interpretive Summary: Consumption of a diet rich in soy product correlated with decreased risk for breast cancer. The isoflavone genistein have been proposed as a candidate compound that is responsible for soy's cancer preventive effects. However, the molecular effects of genistein in mammary epithelial cells remain unclear. Thus to fully realized the cancer preventive effects of genistein further understanding of the molecular mechanism of action of this compound would be important. The present study we explore the interaction of genistein with apoptosis (programmed cell death) pathway. Treatments of mammary cancer cells lead to changes in apoptosis related protein Bak and Bcl-x. This effect of genistein is similar to estradiol and suggestive of a role for genistein in apoptosis pathway. These results provide additional insight into the molecular actions of genistein and may aid in better understanding the role of genistein in breast cancer development. This work provide additional information on the molecular effects of genistein and will benefit scientist working on cancer prevention field.

Technical Abstract: Southeast Asian women have a lower rate of breast cancer compared with their counterparts in western countries and the difference in soybean consumption has been claimed to be a major contributing factor. Genistein is the most studied phytochemical in the soybean. An anti-estrogenic effect is believed to play a crucial part in its chemopreventive mechanism. In the present study, we expressed estrogen receptor (ER) in an ER-negative cell line, HepG2, to investigate the pro- and anti-oestrogenic effect of genistein on the ER transcriptional activity. Genistein by itself had an estimated concentration that induced 50% of the maximum response (EC50) of 2 5mM for the binding to ER-a. In these experiments, genistein concentration as high as 50 mM could not reduce the oestrogen response element-driven luciferase activities initiated by estradiol. Instead, genistein potentiated the ER transactivational activity while cell death was detected. On the other hand, an increased Bak and a reduced Bcl-x(L) was observed at 50 mM-genistein by Western analysis. The combined effect of these two proteins could be important in the apoptotic process. Since plasma genistein 50mM has never been documented following consuming of soybean or soybean products, the present study does not support the notion that dietary soybean exerts its chemopreventive effect through antagonizing ER.