Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy

• Published in: International journal of molecular sciences 2020-10, Vol.21 (21), p.7941
• Main Authors: Dong, Lanfeng, Gopalan, Vinod, Holland, Olivia, Neuzil, Jiri
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; anti-cancer strategy; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Binding sites; Bioenergetics; Biosynthesis; Cancer; Cancer therapies; Cell death; Citric Acid Cycle - drug effects; Clinical Trials as Topic; Dehydrogenases; Disease Progression; Drug delivery; Drug resistance; Drug Resistance, Neoplasm - drug effects; Electron transport; Electron transport chain; Electron Transport Chain Complex Proteins - drug effects; Electron Transport Chain Complex Proteins - metabolism; Gene Expression Regulation, Neoplastic - drug effects; Homeostasis; Humans; Metabolism; Metabolites; mitocans; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial DNA; mitochondrial targeting; Molecular Targeted Therapy; Neoplasms - drug therapy; Neoplasms - metabolism; Organelles; Oxidation-Reduction - drug effects; Respiration; Review; Signal transduction; Signal Transduction - drug effects; Tricarboxylic acid cycle; Tumorigenesis; Tumors; Vitamin E
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21217941

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.