title: Genistein induces cell apoptosis in MDA-MB-231 breast cancer cells via the mitogen-activated protein kinase pathway.
abstract: Genistein, an isoflavonoid present in soybeans, exhibits anti-carcinogenic effects. Several studies have shown that genistein inhibits cell proliferation and triggers apoptosis in human breast cancer cells. In this study, we assessed the role of the MEK-ERK cascade in the regulation of genistein-mediated cell apoptosis in MDA-MB-231 cells. The results indicate that genistein, in a concentration-dependent manner, suppresses the protein levels of MEK5, total ERK5, and phospho-ERK5, effects that are consistent with inhibition of cell growth and induction of apoptosis. Exposure of these cells to genistein results in a concentration-dependent decrease in NF-kappaB/p65 protein levels and DNA-binding activity of NF-kappaB. Genistein down-regulates Bcl-2 and up-regulates Bax. NF-kappaB binding sites are present in the promoter of Bcl-2, suggesting that genistein might inhibit the expression of Bcl-2 through down-regulation of NF-kappaB. Exposure of MDA-MB-231 cells to genistein results in cleavage of caspase-3 and induction of caspase-3 activity in a concentration-dependent manner. Genistein inhibits NF-kappaB activity via the MEK5/ERK5 pathway; it also inhibits cell growth and induces apoptosis. In conclusion, inhibition of the MEK5/ERK5/NF-kappaB pathway may be an important mechanism by which genistein suppresses cell growth and induces apoptosis.
authors.affiliation: The Key Laboratory of Reproductive Medicine of Jiangsu Province, Institute of Toxicology, Nanjing Medical University, No. 140 Hanzhong Road, Jiangsu, Nanjing 210029, China. uiuclz@126.com
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Baoqing
authors.initials: B
authors.lastname: Mo
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hu
authors.forename: Huaqing
authors.initials: H
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Qi
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Jida
authors.initials: J
authors.lastname: Xu