Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy
Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy
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DOI：
10.4161/cc.4.10.2061
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发表时间：
2005-10-01
期刊：
影响因子：
4.3
通讯作者：
Horwitz, SB
中科院分区：
文献类型：
--
作者：
Ikui, AE;Yang, CPH;Horwitz, SB
紫杉醇被广泛用于治疗人类癌症。其在细胞中的作用机制取决于药物浓度。在低浓度的紫杉醇（5 - 10 nM）下，细胞在没有有丝分裂停滞的情况下表现出异常的有丝分裂，包括非整倍性。在较高浓度的紫杉醇（> 20 nM）下，细胞周期在中期被纺锤体检查点激活阻断。在这里，我们证明，低浓度的紫杉醇导致有丝分裂延迟，并导致在退出有丝分裂后的非整倍体细胞群体。低浓度的紫杉醇在有丝分裂后解离p55 CDC-Mad 2或p55 CDC-BubR 1复合物，而高浓度的紫杉醇维持蛋白复合物的形成，导致有丝分裂阻滞。低浓度紫杉醇诱导的细胞凋亡和非整倍体可能是由于纺锤体检查点缺陷引起的染色体错误分离。
Taxol is widely used for the treatment of human cancer. Its mechanism of action in cells is dependent on drug concentration. At low concentrations of Taxol ( 5 - 10 nM), cells exhibit aberrant mitosis, including aneuploidy, in the absence of mitotic arrest. At higher concentrations of Taxol (> 20 nM), the cell cycle is blocked at metaphase by spindle checkpoint activation. Here we demonstrate that low concentrations of Taxol cause mitotic delay, and result in an aneuploid population of cells after exit from mitosis. Low concentrations of Taxol dissociated p55CDC-Mad2 or p55CDC-BubR1 complexes after mitosis, whereas high concentrations of Taxol sustained the protein complex formation leading to mitotic block. The induction of apoptosis and aneuploidy by low concentrations of Taxol may result from chromosome missegregation caused by spindle checkpoint defects.