Abstract
Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and cell death. Increasing evidence suggests that mitochondrial metabolism and functions are indispensable in tumorigenesis and cancer progression, rendering mitochondria and mitochondrial functions as plausible targets for anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting of mitochondria and their functions to combat cancer, including targeting mitochondrial metabolism, the electron transport chain and tricarboxylic acid cycle, mitochondrial redox signalling pathways, and ROS homeostasis. We highlight that delivering anti-cancer drugs into mitochondria exhibits enormous potential for future cancer therapeutic strategies, with a great advantage of potentially overcoming drug resistance. Mitocans, exemplified by mitochondrially targeted vitamin E succinate and tamoxifen (MitoTam), selectively target cancer cell mitochondria and efficiently kill multiple types of cancer cells by disrupting mitochondrial function, with MitoTam currently undergoing a clinical trial.
Highlights
Mitochondria are dynamic intracellular organelles with their own DNA
Glycolysis was traditionally considered as the major source of energy in cancer cells, consistent with the so-called “Warburg effect” first suggested almost a century ago, referring to the elevated uptake of glucose that characterizes the majority of cancers, the mitochondrial function known as oxidative phosphorylation (OXPHOS) has been recently recognized to play a key role in oncogenesis [2,3]
The electron transport chain (ETC) function is pivotal for mitochondrial respiration, and that ETC function is necessary for dihydroorotate dehydrogenase (DHODH)
Summary
Mitochondria are dynamic intracellular organelles with their own DNA (mitochondrial DNA, mtDNA). We have recently proposed the term ‘mitocans’, an acronym derived from the terms mitochondria and cancer, a group of compounds with anti-cancer activity exerted via their molecular targets within mitochondria, some mitocans being selective for malignant tissues [10]. This classification has been used by others, as exemplified by a recent paper [11]. Sci. 2020, 21, 7941 targeting mitochondria and their various functions contribute to novel anti-cancer strategies with high therapeutic potential These strategies include agents that target ETC and OXPHOS, glycolysis, the tricarboxylic acid (TCA).
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