Induction of mitosis-mediated apoptosis by sodium arsenite in HeLaS3 cells
Induction of mitosis-mediated apoptosis by sodium arsenite in HeLaS3 cells
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DOI：
10.1016/s0006-2952(00)00397-x
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发表时间：
2000-09-15
影响因子：
5.8
通讯作者：
Lee, TC
中科院分区：
文献类型：
--
作者：
Huang, SC;Huang, CYF;Lee, TC
砷已被有效地用作治疗急性早幼粒细胞白血病患者的化疗药物。大量研究表明砷会诱导多种细胞类型的凋亡。在本研究中，我们发现，经过亚砷酸盐处理的 HeLa S3 细胞有 35% 的有丝分裂被抑制。从亚砷酸盐处理释放后，超过80%的亚砷酸盐停滞的有丝分裂细胞随后经历了凋亡，如不合时宜的核膜重构、DNA梯的出现、染色质浓缩以及caspase 3和9的激活所表明的。在探索这些细胞如何进入凋亡机制时，我们发现有丝分裂指数和凋亡频率之间存在负相关。 Percoll 密度梯度分级和流式细胞术分析表明，亚砷酸盐诱导的有丝分裂介导的细胞凋亡伴随着细胞周期蛋白 B 降解延迟和有丝分裂退出改变。此外，用星形孢菌素或 2-氨基嘌呤处理亚砷酸盐抑制的有丝分裂细胞会导致细胞周期蛋白 B 快速降解，使这些细胞进入间期而不进行细胞分裂，并消除细胞凋亡。这些结果表明细胞凋亡发生在异常退出有丝分裂的亚砷酸盐抑制的有丝分裂细胞中。 (C) 2000 爱思唯尔科学公司。
Arsenic has been used effectively as a chemotherapeutic drug for the treatment of acute promyelocytic leukemia patients. Numerous studies have demonstrated that arsenic induces apoptosis in various cell types. In the present study, we showed that similar to 35% of arsenite-treated HeLa S3 cells arrested in mitosis. After release from arsenite treatment, more than 80% of arsenite-arrested mitotic cells subsequently underwent apoptosis, as indicated by anachronistic nuclear envelope reformation, DNA ladder occurrence, chromatin condensation, and activation of caspases 3 and 9. In exploring how these cells entered apoptosis mechanistically, we found an inverse correlation between mitotic indexes and apoptotic frequencies. As shown by using Percoll density gradient fractionation and flow cytometric analysis, the mitosis-mediated apoptosis induced by arsenite was accompanied by delayed cyclin B degradation and altered mitotic exit. Furthermore, treatment of arsenite-arrested mitotic cells with staurosporine or 2-aminopurine resulted in a rapid degradation of cyclin B, moved these cells forward to interphase without cell division, and abrogated apoptosis. These results suggest that apoptosis occurs in arsenite-arrested mitotic cells that exit mitosis abnormally. (C) 2000 Elsevier Science Inc.