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Role of senescence and mitotic catastrophe in cancer therapy

机译:衰老和有丝分裂灾难在癌症治疗中的作用

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Senescence and mitotic catastrophe (MC) are two distinct crucial non-apoptotic mechanisms, often triggered in cancer cells and tissues in response to anti-cancer drugs. Chemotherapeuticals and myriad other factors induce cell eradication via these routes. While senescence drives the cells to a state of quiescence, MC drives the cells towards death during the course of mitosis. The senescent phenotype distinguishes tumor cells that survived drug exposure but lost the ability to form colonies from those that recover and proliferate after treatment. Although senescent cells do not proliferate, they are metabolically active and may secrete proteins with potential tumor-promoting activities. The other anti-proliferative response of tumor cells is MC that is a form of cell death that results from abnormal mitosis and leads to the formation of interphase cells with multiple micronuclei. Different classes of cytotoxic agents induce MC, but the pathways of abnormal mitosis differ depending on the nature of the inducer and the status of cell-cycle checkpoints. In this review, we compare the two pathways and mention that they are activated to curb the growth of tumors. Altogether, we have highlighted the possibilities of the use of senescence targeting drugs, mitotic kinases and anti-mitotic agents in fabricating novel strategies in cancer control.
机译:衰老和有丝分裂灾难(MC)是两种截然不同的关键非凋亡机制,通常是在抗癌药的响应下在癌细胞和组织中触发的。化学疗法和许多其他因素通过这些途径诱导细胞根除。衰老使细胞进入静止状态,而MC使细胞在有丝分裂过程中死亡。衰老表型将幸免于药物暴露但失去形成集落的能力的肿瘤细胞与那些在治疗后恢复并增殖的肿瘤细胞区分开来。尽管衰老细胞不增殖,但它们具有代谢活性,并可能分泌具有潜在促肿瘤活性的蛋白质。肿瘤细胞的另一种抗增殖反应是MC,它是细胞死亡的一种形式,是由于异常的有丝分裂导致的,并导致形成具有多个微核的相间细胞。不同种类的细胞毒性剂诱导MC,但异常的有丝分裂途径取决于诱导剂的性质和细胞周期检查点的状态。在这篇综述中,我们比较了这两种途径,并提到它们被激活以抑制肿瘤的生长。总之,我们已经强调了在设计新的癌症控制策略中使用衰老靶向药物,有丝分裂激酶和抗有丝分裂剂的可能性。

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