Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells.
Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells.
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DOI：
10.1038/srep18046
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发表时间：
2015-12-11
影响因子：
4.6
通讯作者：
Palti Y
中科院分区：
文献类型：
--
作者：
Giladi M;Schneiderman RS;Voloshin T;Porat Y;Munster M;Blat R;Sherbo S;Bomzon Z;Urman N;Itzhaki A;Cahal S;Shteingauz A;Chaudhry A;Kirson ED;Weinberg U;Palti Y
肿瘤治疗电场（TTFields）是低强度、中频、交变电场。TTFields是一种独特的抗有丝分裂治疗方式，以连续、无创的方式输送至肿瘤区域。先前假设，通过在有丝分裂期间对高极性细胞内元件施加定向力，TTFields可破坏纺锤体微管的正常组装。然而，将TTFields与微管效应直接联系起来的证据有限。在这里，我们报告了TTFields降低了聚合微管蛋白和总微管蛋白之间的比率，并阻止了正确的有丝分裂纺锤体组装。TTFields诱导的异常有丝分裂事件导致子细胞的异常染色体分离、细胞多核化和半胱天冬酶依赖性凋亡。TTFields对细胞活力和克隆形成存活率的影响主要取决于细胞分裂速率。我们表明，通过延长暴露于TTFields的持续时间，缓慢分裂的细胞受到的影响程度与快速分裂的细胞相似。
Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields. TTFields are a unique anti-mitotic treatment modality delivered in a continuous, noninvasive manner to the region of a tumor. It was previously postulated that by exerting directional forces on highly polar intracellular elements during mitosis, TTFields could disrupt the normal assembly of spindle microtubules. However there is limited evidence directly linking TTFields to an effect on microtubules. Here we report that TTFields decrease the ratio between polymerized and total tubulin, and prevent proper mitotic spindle assembly. The aberrant mitotic events induced by TTFields lead to abnormal chromosome segregation, cellular multinucleation, and caspase dependent apoptosis of daughter cells. The effect of TTFields on cell viability and clonogenic survival substantially depends upon the cell division rate. We show that by extending the duration of exposure to TTFields, slowly dividing cells can be affected to a similar extent as rapidly dividing cells.