...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Post-slippage multinucleation renders cytotoxic variation in anti-mitotic drugs that target the microtubules or mitotic spindle
【24h】

Post-slippage multinucleation renders cytotoxic variation in anti-mitotic drugs that target the microtubules or mitotic spindle

机译：后滑动型多核酸蛋白毒性药物的细胞毒性变异呈靶向微管或有丝分裂主轴的抗筛选药物

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

One common cancer chemotherapeutic strategy is to perturb cell division with anti-mitotic drugs. Paclitaxel, the classic microtubule-targeting anti-mitotic drug, so far still outperforms the newer, more spindle-specific anti-mitotics in the clinic, but the underlying cellular mechanism is poorly understood. In this study we identified post-slippage multinucleation, which triggered extensive DNA damage and apoptosis after drug-induced mitotic slippage, contributes to the extra cytotoxicity of paclitaxel in comparison to the spindle-targeting drug, Kinesin-5 inhibitor. Based on quantitative single-cell microscopy assays, we showed that attenuation of the degree of post-slippage multinucleation significantly reduced DNA damage and apoptosis in response to paclitaxel, and that post-slippage apoptosis was likely mediated by the p53-dependent DNA damage response pathway. Paclitaxel appeared to act as a double-edge sword, capable of killing proliferating cancer cells both during mitotic arrest and after mitotic slippage by inducing DNA damage. Our results thus suggest that to predict drug response to paclitaxel and anti-mitotics in general, 2 distinct sets of bio-markers, which regulate mitotic and post-slippage cytotoxicity, respectively, may need to be considered. Our findings provide important new insight not only for elucidating the cytotoxic mechanisms of paclitaxel, but also for understanding the variable efficacy of different anti-mitotic chemotherapeutics.
机译：一种常见的癌症化学治疗策略是用抗丝体药物扰乱细胞分裂。紫杉醇，经典的微管靶向抗丝分裂药物，到目前为止仍然优于临床临床的更新，更多的主轴特异性抗病毒理学，但潜在的细胞机制理解得很差。在这项研究中，我们鉴定了术后多核，它在药物诱导的有丝分裂后引发了广泛的DNA损伤和细胞凋亡，促使紫杉醇的额外细胞毒性与主轴靶向药物Kinesin-5抑制剂相比。基于定量的单细胞显微镜测定，我们表明，衰减后的衰减多核的程度显着降低了紫杉醇的DNA损伤和凋亡，并且可通过P53依赖性DNA损伤响应途径介导的滑后凋亡。紫杉醇似乎充当双刃剑，能够通过诱导DNA损伤在有丝分裂骤停和丝分裂后杀死增殖癌细胞。因此，我们的结果表明，为了预测对紫杉醇和抗病学的药物反应，通常可以考虑调节有丝分裂和滑后细胞毒性的不同组的生物标志物。我们的调查结果不仅为阐明了紫杉醇的细胞毒性机制提供了重要的新洞察力，而且还可理解不同抗丝体化学治疗剂的可变疗效。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号