线粒体离子通道促进癌细胞化学抵抗
线粒体离子通道是新兴的肿瘤学靶标,因为对这些离子转运蛋白的调节可能会影响线粒体膜电位,氧化磷酸化效率和活性氧的产生。反过来,这些因素会影响细胞色素c的释放,这是线粒体凋亡过程中不返回的点。当前使用的许多化学疗法会诱导程序性细胞死亡,从而导致DNA损伤并随后激活p53依赖性途径,最终导致细胞色素c从线粒体膜间空间释放。如本综述中所概述的那样,正在出现一种观点,即位于该细胞器中的离子通道在几种情况下可通过阻止药物诱导的细胞凋亡来解释癌细胞对经典化疗药物的耐药性。因此,这些通道活性的药理学调节可能有助于对抗不同类型癌细胞的化学耐药性。**
Contribution of Mitochondrial Ion Channels to Chemo-Resistance in Cancer Cells
Mitochondrial ion channels are emerging oncological targets, as modulation of these ion-transporting proteins may impact on mitochondrial membrane potential, efficiency of oxidative phosphorylation and reactive oxygen production. In turn, these factors affect the release of cytochrome c, which is the point of no return during mitochondrial apoptosis. Many of the currently used chemotherapeutics induce programmed cell death causing damage to DNA and subsequent activation of p53-dependent pathways that finally leads to cytochrome c release from the mitochondrial inter-membrane space. The view is emerging, as summarized in the present review, that ion channels located in this organelle may account in several cases for the resistance that cancer cells can develop against classical chemotherapeutics, by preventing drug-induced apoptosis. Thus, pharmacological modulation of these channel activities might be beneficial to fight chemo-resistance of different types of cancer cells.
pmid: 31159324 Cancers (Basel) 影响因子: 6.162 发表日期: 20190531 官网 免费下载
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