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首页> 外文期刊>Anti-cancer drugs >Genistein-induced apoptosis of human breast cancer MCF-7 cells involves calpain-caspase and apoptosis signaling kinase 1-p38 mitogen-activated protein kinase activation cascades.
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Genistein-induced apoptosis of human breast cancer MCF-7 cells involves calpain-caspase and apoptosis signaling kinase 1-p38 mitogen-activated protein kinase activation cascades.

机译:金雀异黄素诱导的人乳腺癌MCF-7细胞凋亡涉及钙蛋白酶半胱天冬酶和凋亡信号激酶1-p38丝裂原活化蛋白激酶活化级联反应。

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摘要

The molecular mechanisms of genistein-induced apoptosis of human breast cancer MCF-7 cells were investigated. Genistein showed 50% cell growth inhibition at IC50=27.5+/-0.8 micromol/l in 24 h incubation under 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay conditions. Genistein is known to express both cell growth activity at nanomolar concentrations and anti-cell growth activity at micromolar concentrations. It was found that genistein at 100 micromol/l concentration effectively induced apoptosis of MCF-7 cells in 24 h. Genistein-induced apoptosis involved activation of calpain, caspase 7 and poly(ADP ribose) polymerase. Dantrolene, an inhibitor of Ca release from the endoplasmic reticulum, inhibited genistein-induced activation of calpain and caspase 7, in addition to effectively negating genistein-induced apoptosis. MCF-7 cells treated with genistein also showed increased phosphorylation of p38 mitogen-activated protein kinase, whereas no effect was observed for extracellular signal-regulating kinase 1/2. Phosphorylation of apoptosis signaling kinase 1, an upstream regulator of p38 mitogen-activated protein kinase, was also increased by genistein treatment. Genistein-induced phosphorylation of apoptosis signaling kinase 1 and p38 mitogen-activated protein kinase was diminished by the presence of dantrolene. These results suggest that genistein-induced apoptosis in MCF-7 cells is mediated through calpain-caspase 7 and apoptosis signaling kinase 1-p38 mitogen-activated protein kinase activation cascades that involve Ca release from the endoplasmic reticulum.
机译:研究了染料木黄酮诱导人乳腺癌MCF-7细胞凋亡的分子机制。 Genistein在3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑测定条件下孵育24小时后,在IC50 = 27.5 +/- 0.8 micromol / l下显示50%的细胞生长抑制。已知染料木黄酮在纳摩尔浓度下既表达细胞生长活性,又在微摩尔浓度下表达抗细胞生长活性。发现金雀异黄素浓度为100 micromol / l可以在24小时内有效诱导MCF-7细胞凋亡。金雀异黄素诱导的细胞凋亡涉及钙蛋白酶,胱天蛋白酶7和聚ADP核糖聚合酶的激活。 Dantrolene,一种从内质网释放Ca的抑制剂,除了有效地抑制了染料木素诱导的细胞凋亡外,还抑制了染料木素诱导的钙蛋白酶和caspase 7的活化。金雀异黄素处理过的MCF-7细胞也显示出p38丝裂原活化蛋白激酶的磷酸化增加,而细胞外信号调节激酶1/2则未见效果。金雀异黄素的处理也增加了凋亡信号激酶1(p38丝裂原活化蛋白激酶的上游调节剂)的磷酸化。金雀异黄素诱导的细胞凋亡信号激酶1和p38丝裂原活化蛋白激酶的磷酸化由于丹特罗的存在而减少。这些结果表明,染料木素诱导的MCF-7细胞凋亡是通过钙蛋白酶-半胱氨酸蛋白酶7和凋亡信号激酶1-p38丝裂原激活的蛋白激酶激活级联介导的,其中Ca从内质网释放。

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