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Novel Mitochondria-targeted Drugs for Cancer Therapy

Author(s):

Jindriska Leischner Fialova, Martina Raudenska, Milan Jakubek, Zdenek Kejik, Pavel Martasek, Petr Babula, Adam Matkowski, Petr Filipensky and Michal Masarik*   Pages 1 - 17 ( 17 )

Abstract:


The search for mitochondria-targeted drugs has dramatically risen over the last decade. Mitochondria are essential organelles serving not only as a powerhouse of the cell but also as a key player in cell proliferation and cell death. Their central role in the energetic metabolism, calcium homeostasis and apoptosis makes them an intriguing field of interest for cancer pharmacology. In cancer cells, many mitochondrial signaling and metabolic pathways are altered. These changes contribute to cancer development and progression. Due to changes in the mitochondrial metabolism and changes in a membrane potential, cancer cells are more susceptible to mitochondria-targeted therapy and the loss of functional mitochondria leads to arrest of cancer progression and/or a cancer cell death. Identification of mitochondrial changes specific for tumor growth and progression, a rational development of new mitochondria-targeted drugs and research on delivery agents led to the advance of this promising area. This review will highlight the current findings in mitochondrial biology which are important for cancer initiation, progression and resistance and discuss approaches of cancer pharmacology with a special focus to the anti-cancer drugs referred to as ‘mitocans’.

Keywords:

mitochondria, targeting, metabolism, cancer, treatment, inhibitors, hexokinase, tricarboxylic acid cycle, respiratory chain, electron transport chain

Affiliation:

Department of Physiology, Faculty of Medicine, Masaryk University / Kamenice 5, CZ-625 00 Brno, Department of Physiology, Faculty of Medicine, Masaryk University / Kamenice 5, CZ-625 00 Brno, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Kateřinská 32, 121 08 Prague 2, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Kateřinská 32, 121 08 Prague 2, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Kateřinská 32, 121 08 Prague 2, Department of Physiology, Faculty of Medicine, Masaryk University / Kamenice 5, CZ-625 00 Brno, Department of Pharmaceutical Biology and Botany, Wroclaw Medical University, 50556 Borowska 211, Department of Urology, St. Anne’s Faculty Hospital, CZ-65691 Brno, Department of Physiology, Faculty of Medicine, Masaryk University / Kamenice 5, CZ-625 00 Brno



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