The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells.
The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells.
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发表时间：
2002-11
影响因子：
5.7
通讯作者：
J. Sasaki;R. Ramesh;S. Chada;Y. Gomyo;J. Roth;T. Mukhopadhyay
中科院分区：
文献类型：
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作者：
J. Sasaki;R. Ramesh;S. Chada;Y. Gomyo;J. Roth;T. Mukhopadhyay
微管在细胞分裂中具有关键作用，因此已经开发了各种微管抑制剂作为抗癌药物。在这项研究中，我们评估甲苯咪唑（MZ），微管破坏驱虫剂，表现出在体外和体内有效的抗肿瘤特性。用MZ处理肺癌细胞系引起有丝分裂停滞，随后是具有半胱天冬酶激活和细胞色素c释放特征的凋亡细胞死亡。MZ诱导有丝分裂癌细胞中异常纺锤体形成，并增强微管蛋白的解聚，但MZ的解聚效力低于诺考达唑。小鼠经口给予MZ在皮下给药中引起强烈的抗肿瘤作用。与紫杉醇治疗的小鼠相比，在实验诱导的肺转移中，模型和减少的肺集落没有任何毒性。我们推测肿瘤细胞可能在一个有丝分裂检查点功能上有缺陷，并且对纺锤体抑制剂MZ敏感。异常纺锤体形成可能是决定细胞是否发生凋亡的关键因素，而强微管抑制剂即使在正常细胞中也会引起毒性。
Microtubules have a critical role in cell division, and consequently various microtubule inhibitors have been developed as anticancer drugs. In this study, we assess mebendazole (MZ), a microtubule-disrupting anthelmintic that exhibits a potent antitumor property both in vitro and in vivo. Treatment of lung cancer cell lines with MZ caused mitotic arrest, followed by apoptotic cell death with the feature of caspase activation and cytochrome c release. MZ induces abnormal spindle formation in mitotic cancer cells and enhances the depolymerization of tubulin, but the efficacy of depolymerization by MZ is lower than that by nocodazole. Oral administration of MZ in mice elicited a strong antitumor effect in a s.c. model and reduced lung colonies in experimentally induced lung metastasis without any toxicity when compared with paclitaxel-treated mice. We speculate that tumor cells may be defective in one mitotic checkpoint function and sensitive to the spindle inhibitor MZ. Abnormal spindle formation may be the key factor determining whether a cell undergoes apoptosis, whereas strong microtubule inhibitors elicit toxicity even in normal cells.