Induction of apoptosis in breast cancer cells MDA-MB-231 by genistein.
Breast cancer is the most common cancer among American women, whereas Asian women, who consume a traditional diet high in soy products, have a relatively low incidence. Genistein is a prominent isoflavonoid in soy products and has been proposed as the agent responsible for lowering the rate of breast cancer in Asian women. We investigated the effects of genistein on cell growth and apoptosis-related gene expression in breast cancer cells MDA-MB-231. We found up-regulation of Bax and p21WAF1 expressions and down-regulation of Bcl-2 and p53 expression in genistein-treated cells. Furthermore, DNA ladder formation, CPP32 activation, and PARP cleavage were observed after treatment with genistein, indicating apoptotic cell deaths. Flow cytometry with 7-amino actinomycin D staining showed that the number of apoptotic cells increased with longer treatment of genistein. From these results, we conclude that genistein inhibits the growth of MDA-MB-231 breast cancer cells, regulates the expression of apoptosis-related genes, and induces apoptosis through a p53-independent pathway. The up-regulation of Bax and p21WAF1 may be the molecular mechanisms by which genistein induces apoptosis, however, further definitive studies are needed. These results suggest that genistein may be a potentially effective chemopreventive or therapeutic agent against breast cancer.
Li
Y
Y
Department of Pathology, Karmanos Cancer Institute at Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Upadhyay
S
S
Bhuiyan
M
M
Sarkar
F H
FH
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D016158:Genes, p53; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019833:Genistein