caa a22 4500 463208072 CHVBK 20180405153131.0 cr unu---uuuuu 170326e20070201xx s 000 0 eng 10.1007/s10863-006-9060-z doi (NATIONALLICENCE)springer-10.1007/s10863-006-9060-z Mitocans as anti-cancer agents targeting mitochondria: lessons from studies with vitamin E analogues, inhibitors of complex II [Elektronische Daten] [Jiri Neuzil, Jeffrey Dyason, Ruth Freeman, Lan-Feng Dong, Lubomir Prochazka, Xiu-Fang Wang, Immo Scheffler, Stephen Ralph] 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. Springer Science+Business Media, LLC, 2007 Mitocans nationallicence Mitochondria nationallicence Complex II nationallicence Coenzyme Q nationallicence Vitamin E analogues nationallicence Superoxide nationallicence Apoptosis nationallicence Cancer nationallicence Neuzil Jiri Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia aut Dyason Jeffrey Institute for Glycomics, Griffith University, Southport, Qld, Australia aut Freeman Ruth Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia aut Dong Lan-Feng Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia aut Prochazka Lubomir Veterinary Research Institute, Brno, Czech Republic aut Wang Xiu-Fang Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia aut Scheffler Immo Division of Biology, Molecular Biology Section, University of California, San Diego, CA, USA aut Ralph Stephen Genomic Research Centre, Griffith University, Southport, Qld, Australia aut Journal of Bioenergetics and Biomembranes Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 39/1(2007-02-01), 65-72 0145-479X 39:1<65 2007 39 10863 https://doi.org/10.1007/s10863-006-9060-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10863-006-9060-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Neuzil Jiri Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia aut NATIONALLICENCE 700 1- Dyason Jeffrey Institute for Glycomics, Griffith University, Southport, Qld, Australia aut NATIONALLICENCE 700 1- Freeman Ruth Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia aut NATIONALLICENCE 700 1- Dong Lan-Feng Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia aut NATIONALLICENCE 700 1- Prochazka Lubomir Veterinary Research Institute, Brno, Czech Republic aut NATIONALLICENCE 700 1- Wang Xiu-Fang Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia aut NATIONALLICENCE 700 1- Scheffler Immo Division of Biology, Molecular Biology Section, University of California, San Diego, CA, USA aut NATIONALLICENCE 700 1- Ralph Stephen Genomic Research Centre, Griffith University, Southport, Qld, Australia aut NATIONALLICENCE 773 0- Journal of Bioenergetics and Biomembranes Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 39/1(2007-02-01), 65-72 0145-479X 39:1<65 2007 39 10863 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer