Genistein induces cell apoptosis in MDA-MB-231 breast cancer cells via the mitogen-activated protein kinase pathway
Genistein induces cell apoptosis in MDA-MB-231 breast cancer cells via the mitogen-activated protein kinase pathway
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金雀异黄素通过丝裂原激活蛋白激酶途径诱导 MDA-MB-231 乳腺癌细胞凋亡
DOI：
10.1016/j.tiv.2008.08.001
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发表时间：
2008-10-01
影响因子：
3.2
通讯作者：
Xu, Jida
中科院分区：
文献类型：
--
作者：
Li, Zhong;Li, Jing;Xu, Jida
染料木黄酮是一种存在于大豆中的生物碱，具有抗癌作用。几项研究表明，染料木黄酮抑制细胞增殖，并引发人类乳腺癌细胞凋亡。在这项研究中，我们评估了MEK-ERK级联在染料木素介导的MDA-MB-231细胞凋亡的调节中的作用。结果表明，染料木黄酮，以浓度依赖性的方式，抑制蛋白质水平的MEK 5，总ERK 5，磷酸化ERK 5，效果是一致的细胞生长的抑制和诱导细胞凋亡。这些细胞暴露于染料木黄酮导致NF-κ B/p65蛋白水平和NF-κ B的DNA结合活性的浓度依赖性降低。Genistein下调Bcl-2，上调Bax。Bcl-2基因启动子区存在NF-κ B结合位点，提示Genistein可能通过下调NF-κ B而抑制Bcl-2的表达。MDA-MB-231细胞暴露于染料木黄酮导致半胱天冬酶-3的切割和半胱天冬酶-3活性的诱导，以浓度依赖性的方式。染料木黄酮通过MEK 5/ERK 5途径抑制NF-κ B活性：它还抑制细胞生长并诱导细胞凋亡。总之，抑制MEK 5/ERK 5/NF-κ B通路可能是染料木素抑制细胞生长和诱导凋亡的重要机制。(C)2008爱思唯尔有限公司版权所有。
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-kappa B/p65 protein levels and DNA-binding activity of NF-kappa B. Genistein down-regulates Bcl-2 and up-regulates Bax. NF-kappa B binding sites are present in the promoter of Bcl2, suggesting that genistein might inhibit the expression of Bcl-2 through down-regulation of NF-kappa B. 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-kappa B activity via the MEK5/ERK5 pathway: it also inhibits cell growth and induces apoptosis. In conclusion, inhibition of the MEK5/ERK5/NF-KB pathway may be an important mechanism by which genistein suppresses cell growth and induces apoptosis. (C) 2008 Elsevier Ltd. All rights reserved.