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首页> 外文期刊>Life sciences >Gossypol induces apoptosis in human PC-3 prostate cancer cells by modulating caspase-dependent and caspase-independent cell death pathways
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Gossypol induces apoptosis in human PC-3 prostate cancer cells by modulating caspase-dependent and caspase-independent cell death pathways

机译：棉酚通过调节caspase依赖性和caspase依赖性细胞死亡途径诱导人PC-3前列腺癌细胞凋亡

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The rate of gaossypol-induced apoptosis does not correlate very well with the same dose of gossypol-induced cell growth inhibition, indicating an anti-proliferative effect of gossypol. Using a co-immunoprecipitation assay, it was observed that the level of Bcl-X-L protein bound to Bax was clearly lower than that of Bcl-2 protein at 5 mu M of gossypol treatment, and the level of Bim protein bound to Bcl-X-L was lowered at 20 PM of gossypol treatment for 24 h, implicating that gossypol inhibits the heterodimerization of Bcl-X-L with Bax and Bim. Gossypol-induced apoptosis is partly suppressed by as low as 0.5 mu M, but not abolished by as high as 50 mu M of a broad range caspase inhibitor, Z-VAD-FMK, suggesting that gossypol-induced apoptosis is both caspase-dependent and -independent. Furthermore, the release of apoptosis inducing factor (AIF), which triggers caspase-independent apoptosis, from mitochondria to cytosol was observed in PC-3 cells exposed to gossypol treatment. In conclusion, aossypol inhibits the proliferation and induces apoptosis in PC-3 cells. Gossypol-induced apoptosis is, at least, through inhibiting the heterodimerization of BCI-X-L/Bcl-2 with pro-apoptosis molecules, followed by a caspase-dependent and -independent process which involves the release of AIF from the mitochondria to cytosol. (c) 2006 Elsevier Inc. All rights reserved.
机译：棉酚诱导的细胞凋亡率与相同剂量的棉酚诱导的细胞生长抑制没有很好的相关性，表明棉酚具有抗增殖作用。使用免疫共沉淀测定法观察到，在棉酚处理5μM时，与Bax结合的Bcl-XL蛋白水平明显低于Bcl-2蛋白，并且与Bcl-XL结合的Bim蛋白水平在棉酚治疗20 PM时24h降低24h，表明棉酚抑制Bcl-XL与Bax和Bim的异源二聚化。棉酚诱导的细胞凋亡被低至0.5μM的部分抑制，但高达50μM的宽范围胱天蛋白酶抑制剂Z-VAD-FMK却没有被消除，这表明棉酚诱导的细胞凋亡既依赖于caspase，又依赖于胱天蛋白酶。 -独立。此外，在棉酚处理的PC-3细胞中观察到了凋亡诱导因子（AIF）从线粒体到胞质溶胶的释放，该因子触发caspase依赖性凋亡。总之，奥斯泊酚抑制PC-3细胞的增殖并诱导其凋亡。棉酚诱导的细胞凋亡至少是通过抑制促凋亡分子抑制BCI-X-L / Bcl-2的异二聚化，然后是半胱天冬酶依赖性和非依赖性过程，该过程涉及AIF从线粒体释放到细胞质。 （c）2006 Elsevier Inc.保留所有权利。

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