Mitotic catastrophe results in cell death by caspase-dependent and caspase-independent mechanisms
Mitotic catastrophe results in cell death by caspase-dependent and caspase-independent mechanisms
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DOI：
10.4161/cc.5.1.2267
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发表时间：
2006-01-01
期刊：
影响因子：
4.3
通讯作者：
Portugal, J
中科院分区：
文献类型：
--
作者：
Mansilla, S;Priebe, W;Portugal, J
MDA-MB-231和MCF-7/VP人乳腺癌细胞暴露于蒽环类药物多柔比星和WP 631诱导多倍体，形成多核细胞和细胞死亡的有丝分裂灾难通过半胱天冬酶依赖性和半胱天冬酶非依赖性机制。在这两种细胞系中，WP 631的抗增殖作用高于阿霉素，并且观察到G（2）/M的暂时停止而没有细胞衰老，而在这些细胞中没有发生p53依赖性凋亡。有丝分裂的灾难与坏死，但也与凋亡样死亡，估计与膜联蛋白-V-荧光素和碘化丙啶的差异细胞染色。观察到药物诱导的c-myc和p21（WAF 1）表达及其各自蛋白水平的变化。它们依赖于细胞系、所用蒽环类药物及其浓度，并且它们与细胞周期从G（2）到有丝分裂的进程一致。caspase-2和caspase-3的显著活化仅在用多柔比星处理的MDA-MB-231细胞中观察到，而用WP 631处理的MDA-MB-231细胞中未观察到，表明caspase可能不是通过有丝分裂灾难发生细胞死亡的强制性因素。在MCF-7/VP细胞中，不表达功能性caspase-3，也诱导有丝分裂灾难。
Exposure of MDA-MB-231 and MCF-7/VP human breast carcinoma cells to the anthracyclines doxorubicin and WP631 induced polyploidy, formation of multinucleated cells and cell death by mitotic catastrophe through caspase-dependent and caspase-independent mechanisms. In both cell lines, the anti-proliferative effect of WP631 was higher than that of doxorubicin and a transient halt in G(2)/M was observed without cell senescence, while p53-dependent apoptosis did not occur in these cells. Mitotic catastrophe was linked to necrosis, but also to apoptosis-like death, estimated by differential cell staining with annexin-V-fluorescein and propidium iodide. Drug-induced changes in the expression of c-myc and p21(WAF1), and in their respective protein levels, were observed. They depended on the cell line, the anthracycline used and its concentration, and they were consistent with the cell cycle progression through G(2) to mitosis. Significant activation of caspase-2 and caspase-3 was only observed in MDA-MB-231 cells treated with doxorubicin but not with WP631, indicating that caspases may be not mandatory for the occurrence of cell death through mitotic catastrophe. In MCF-7/VP cells, which do not express functional caspase-3, mitotic catastrophe was also induced.