Journal of Bioenergetics and Biomembranes

, Volume 39, Issue 1, pp 65–72

Mitocans as anti-cancer agents targeting mitochondria: lessons from studies with vitamin E analogues, inhibitors of complex II

Authors

    • Apoptosis Research Group, School of Medical ScienceGriffith University
    • Molecular Therapy Group, Institute of Molecular GeneticsAcademy of Sciences of the Czech Republic
    • Apoptosis Research Group, Heart Foundation Research Centre, Griffith Institute for Health and Medical Research, School of Medical ScienceGriffith University Gold Coast Campus
  • Jeffrey C. Dyason
    • Institute for GlycomicsGriffith University
  • Ruth Freeman
    • Apoptosis Research Group, School of Medical ScienceGriffith University
  • Lan-Feng Dong
    • Apoptosis Research Group, School of Medical ScienceGriffith University
  • Lubomir Prochazka
    • Veterinary Research Institute
  • Xiu-Fang Wang
    • Apoptosis Research Group, School of Medical ScienceGriffith University
  • Immo Scheffler
    • Division of Biology, Molecular Biology SectionUniversity of California
  • Stephen J. Ralph
    • Genomic Research CentreGriffith University
Mini Review

DOI: 10.1007/s10863-006-9060-z

Cite this article as:
Neuzil, J., Dyason, J.C., Freeman, R. et al. J Bioenerg Biomembr (2007) 39: 65. doi:10.1007/s10863-006-9060-z

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.

Keywords

MitocansMitochondriaComplex IICoenzyme QVitamin E analoguesSuperoxideApoptosisCancer

Copyright information

© Springer Science+Business Media, LLC 2007