Genistein-induced apoptosis in MCF-7 cells involves changes in Bak and Bcl-x without evidence of anti-oestrogenic effects.
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 microm for the binding to OR-alpha. In these experiments, genistein concentration as high as 50 microm 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 microm-genistein by Western analysis. The combined effect of these two proteins could be important in the apoptotic process. Since plasma genistein >50 microm 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.
Po
Lai See
LS
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Wang
Thomas T
TT
Chen
Zhen-Yu
ZY
Leung
Lai K
LK
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D013268:Stimulation, Chemical; D015533:Transcriptional Activation / Q000187:drug effects; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein
D016588:Anticarcinogenic Agents; C494772:BAK1 protein, human; C494811:BCL2L1 protein, human; D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; D004958:Estradiol; D019833:Genistein; D008156:Luciferases