Mitocans as anti-cancer agents targeting mitochondria: lessons from studies with vitamin E analogues,inhibitors of complex II |
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Authors: | Jiri Neuzil Jeffrey C. Dyason Ruth Freeman Lan-Feng Dong Lubomir Prochazka Xiu-Fang Wang Immo Scheffler Stephen J. Ralph |
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Affiliation: | (1) Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia;(2) Molecular Therapy Group, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic;(3) Institute for Glycomics, Griffith University, Southport, Qld, Australia;(4) Veterinary Research Institute, Brno, Czech Republic;(5) Division of Biology, Molecular Biology Section, University of California, San Diego, CA, USA;(6) Genomic Research Centre, Griffith University, Southport, Qld, Australia;(7) Apoptosis Research Group, Heart Foundation Research Centre, Griffith Institute for Health and Medical Research, School of Medical Science, Griffith University Gold Coast Campus, Southport, Qld, Australia |
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Abstract: | Recently mitochondria in cancer cells have emerged as the Achilles heel for tumour destruction. Anti-cancer agents specifically targeting cancer cell mitochondria are referred to as ‘mitocans’. These compounds act by destabilising these organelles, unleashing their apoptogenic potential, resulting in the efficient death of malignant cells and suppression of tumour growth. Importantly, at least some mitocans are selective for cancer cells, and these are represented by the group of redox-silent vitamin E analogues, epitomised by α-tocopheryl succinate (α-TOS). This compound has proven itself in pre-clinical models to be an efficient anti-cancer agent, targeting complex II of the respiratory chain to displace ubiquinone binding. We propose that disrupting the electron flow of mitochondrial complex II results in generation of superoxide, triggering mitochondrial destabilisation and initiation of apoptotic pathways. Moreover, α-TOS is selective for cancer cells with their reduced anti-oxidant defenses and lower esterase activity than the normal (non-malignant) counterparts. In this mini-review we discuss the emerging significance of mitocans, as exemplified by α-TOS. Lubomir Prochazka is a visiting student of the Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia. |
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Keywords: | Mitocans Mitochondria Complex II Coenzyme Q Vitamin E analogues Superoxide Apoptosis Cancer |
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