期刊
REDOX BIOLOGY
卷 42, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2020.101846
关键词
Mitochondria; Ion channels; Cancer; Drug targeting; Channel interactions
资金
- Italian Association for Cancer Research [20286]
- Italian Association for Multiple Sclerosis FISM/AISM [284/18/F14]
- CNR InterOmics project (GLIOMICS)
Targeting mitochondrial ion channels with drugs to eliminate cancer cells is a promising approach due to differential expression and/or regulation of these channels in cancer cells compared to healthy cells. Modulation of ion channels can indirectly affect oxidative phosphorylation, which may be crucial for cancer and cancer stem cell survival. Additionally, modulation of mitochondrial ion channels leading to cytochrome c release may be advantageous in overcoming drug resistance.
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.
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