Pharmacological targeting of mitochondria in cancer stem cells: An ancient organelle at the crossroad of novel anti-cancer therapies. (January 2019)

• Record Type: Journal Article
• Authors: Skoda, Jan; Borankova, Karolina; Jansson, Patric J.; Huang, Michael L.-H.; Veselska, Renata; Richardson, Des R.
• Is Part Of: Pharmacological research. Volume 139(2019)
• Page Start: 298
• Page End: 313
• Publication Date: 2019-01
• Subjects: AMPK adenosine monophosphate-activated protein kinase -- α-TOS α-tocopheryl succinate -- BNIP3 B-cell lymphoma 2-interacting protein 3 -- BNIP3L BNIP3-like -- CCCP carbonyl cyanide m-chlorophenylhydrazone -- COX-2 cyclooxygenase-2 -- CPT1 carnitine palmitoyltransferase type 1 -- CSC cancer stem cell -- DRP1 dynamin-related protein 1 -- ERRα estrogen-related receptor α -- ESC embryonic stem cell -- iPSC induced pluripotent stem cell -- LC3 light chain 3 -- Mdivi-1 mitochondrial division inhibitor-1 -- MFF mitochondrial fission factor -- MID49 mitochondrial dynamics protein of 49 kDa -- MID51 mitochondrial dynamics protein of 51 kDa -- MitoVES mitochondrial-targeted derivative of α-TOS -- MOMP mitochondrial outer membrane permeabilization -- OPA1 optic atrophy 1 -- PGC1α peroxisome proliferator-activated receptor gamma coactivator 1-alpha -- PINK1 PTEN-induced putative kinase 1 -- ROS reactive oxygen species -- SC stem cell; Mdivi-1 (CID: 3825829) -- Celecoxib (CID: 2662) -- XCT790 (CID: 6918788) -- Metformin (CID: 4091) -- Bedaquiline (CID: 5388906) -- Doxycycline (CID: 54671203) -- Etomoxir (CID: 9840324) -- Teglicar (CID: 9843897) -- ABT-263 (CID: 24978538) -- ABT-737 (CID: 11228183); Cancer stem cells -- Mitochondria -- Anti-cancer therapeutics -- Mitophagy -- Breast cancer -- Glioblastoma; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2018.11.020
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Mitochondria play vital roles in various cellular processes, ranging from cellular metabolism to signal transduction and cell death regulation. As these properties are critical for cancer growth, the mitochondrion has recently become an attractive target for anti-cancer therapies. In addition, it has come to light that mitochondria are crucially involved in the regulation of stem cell identity, differentiation and fate. A similar role for mitochondria has been also demonstrated in malignant stem-like cells termed cancer stem cells (CSCs), which are implicated in progression and resistance of many tumors. In this review, we summarize different mitochondrial functions reported to promote acquisition and maintenance of CSC phenotype and discuss the rationale for their therapeutic targeting. Particular emphasis is given to therapeutics that act directly through modulation of these mitochondrial functions and have recently emerged as promising anti-CSC drugs in pre-clinical studies. This review highlights the intriguing aspects of mitochondrial biology that may have a crucial role in cancer initiation, progression, and resistance and which might facilitate pharmacological targeting. Indeed, understanding of mitochondrial function in the regulation of CSCs will promote the development of novel CSC-targeted therapeutic strategies, which could significantly improve the long-term survival of cancer patients.