Bcl-2 is not reduced in the death of MCF-7 cells at low genistein concentration.
Soy consumption has been associated with a lower incidence of breast cancer in Southeast Asia. Among the phytochemicals in soy, genistein has been suggested to be chemopreventive. Because genistein is an estrogen-receptor (ER) agonist, the chemopreventive mechanism has been attributed to its ability to compete with estrogen for receptor binding. In this study, we used an ER-positive cell line to investigate the effects of different genistein concentrations on the apoptotic response. The threshold concentration at which a significant number of cells underwent apoptosis was titrated to be 25 micromol/L. At or above this concentration, c-jun N-terminus kinase was activated and Bax and Bcl-2 expression were both elevated. The elevated Bcl-2 protein might neutralize the proapoptotic effect of Bax. Therefore, the mechanism of genistein-induced apoptosis at this concentration might rely largely on the stress pathway rather than the pathway mediated by the Bcl-2 family of proteins.
Leung
L K
LK
Food and Nutritional Sciences Programme, Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Wang
T T
TT
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D016758:Genes, jun; D016158:Genes, p53 / Q000187:drug effects; D019833:Genistein / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D013025:Glycine max; D013312:Stress, Physiological / Q000150:complications / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D051028:bcl-2-Associated X Protein; D019833:Genistein; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases