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Targeting Mitochondrial Ion Channels for Cancer Therapy
Redox Biology ( IF 10.7 ) Pub Date : 2020-12-24 , DOI: 10.1016/j.redox.2020.101846
Ildiko Szabo 1 , Mario Zoratti 2 , Lucia Biasutto 3
Affiliation  

Pharmacological targeting of mitochondrial ion channels is emerging as a promising approach to eliminate cancer cells; as most of these channels are differentially expressed and/or regulated in cancer cells in comparison to healthy ones, this strategy may selectively eliminate the former. Perturbation of ion fluxes across the outer and inner membranes is linked to alterations of redox state, membrane potential and bioenergetic efficiency. This leads to indirect modulation of oxidative phosphorylation, which is/may be fundamental for both cancer and cancer stem cell survival. Furthermore, given the crucial contribution of mitochondria to intrinsic apoptosis, modulation of their ion channels leading to cytochrome c release may be of great advantage in case of resistance to drugs triggering apoptotic events upstream of the mitochondrial phase. In the present review, we give an overview of the known mitochondrial ion channels and of their modulators capable of killing cancer cells. In addition, we discuss state-of-the-art strategies using mitochondriotropic drugs or peptide-based approaches allowing a more efficient and selective targeting of mitochondrial ion channel-linked events.



中文翻译:


靶向线粒体离子通道进行癌症治疗



线粒体离子通道的药理学靶向正在成为消除癌细胞的一种有前途的方法;由于与健康细胞相比,大多数这些通道在癌细胞中表达和/或调节存在差异,因此该策略可以选择性地消除前者。穿过外膜和内膜的离子通量的扰动与氧化还原状态、膜电位和生物能效率的改变有关。这导致氧化磷酸化的间接调节,这对于癌症和癌症干细胞的生存是/可能是基础的。此外,鉴于线粒体对内在细胞凋亡的重要贡献,在对触发线粒体相上游细胞凋亡事件的药物产生耐药性的情况下,调节其离子通道导致细胞色素c释放可能具有很大的优势。在本综述中,我们概述了已知的线粒体离子通道及其能够杀死癌细胞的调节剂。此外,我们讨论了使用线粒体药物或基于肽的方法的最先进策略,可以更有效和选择性地靶向线粒体离子通道相关事件。

更新日期:2020-12-25
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