Li Zhong, Li Jing, Mo Baoqing, Hu Chunyan, Liu Huaqing, Qi Hong, Wang Xinru, Xu Jida
The Key Laboratory of Reproductive Medicine of Jiangsu Province, Institute of Toxicology, Nanjing Medical University, No. 140 Hanzhong Road, Jiangsu, Nanjing 210029, China.
Toxicol In Vitro. 2008 Oct;22(7):1749-53. doi: 10.1016/j.tiv.2008.08.001. Epub 2008 Aug 12.
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.
染料木黄酮是大豆中含有的一种异黄酮，具有抗癌作用。多项研究表明，染料木黄酮可抑制人乳腺癌细胞的增殖并引发细胞凋亡。在本研究中，我们评估了MEK-ERK级联反应在染料木黄酮介导的MDA-MB-231细胞凋亡调控中的作用。结果表明，染料木黄酮以浓度依赖性方式抑制MEK5、总ERK5和磷酸化ERK5的蛋白水平，这些作用与抑制细胞生长和诱导细胞凋亡一致。将这些细胞暴露于染料木黄酮会导致NF-κB/p65蛋白水平和NF-κB的DNA结合活性呈浓度依赖性降低。染料木黄酮下调Bcl-2并上调Bax。Bcl-2启动子中存在NF-κB结合位点，这表明染料木黄酮可能通过下调NF-κB来抑制Bcl-2的表达。将MDA-MB-231细胞暴露于染料木黄酮会导致caspase-3的裂解并以浓度依赖性方式诱导caspase-3活性。染料木黄酮通过MEK5/ERK5途径抑制NF-κB活性；它还抑制细胞生长并诱导细胞凋亡。总之，抑制MEK5/ERK5/NF-κB途径可能是染料木黄酮抑制细胞生长和诱导细胞凋亡的重要机制。
