Journal of Bioenergetics and Biomembranes

, Volume 39, Issue 1, pp 65–72 | Cite as

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

  • Jiri Neuzil
  • Jeffrey C. Dyason
  • Ruth Freeman
  • Lan-Feng Dong
  • Lubomir Prochazka
  • Xiu-Fang Wang
  • Immo Scheffler
  • Stephen J. Ralph
Mini Review

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

Mitocans Mitochondria Complex II Coenzyme Q Vitamin E analogues Superoxide Apoptosis Cancer 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Jiri Neuzil
    • 1
    • 2
    • 7
  • Jeffrey C. Dyason
    • 3
  • Ruth Freeman
    • 1
  • Lan-Feng Dong
    • 1
  • Lubomir Prochazka
    • 4
  • Xiu-Fang Wang
    • 1
  • Immo Scheffler
    • 5
  • Stephen J. Ralph
    • 6
  1. 1.Apoptosis Research Group, School of Medical ScienceGriffith UniversitySouthportAustralia
  2. 2.Molecular Therapy Group, Institute of Molecular GeneticsAcademy of Sciences of the Czech RepublicPragueCzech Republic
  3. 3.Institute for GlycomicsGriffith UniversitySouthportAustralia
  4. 4.Veterinary Research InstituteBrnoCzech Republic
  5. 5.Division of Biology, Molecular Biology SectionUniversity of CaliforniaSan DiegoUSA
  6. 6.Genomic Research CentreGriffith UniversitySouthportAustralia
  7. 7.Apoptosis Research Group, Heart Foundation Research Centre, Griffith Institute for Health and Medical Research, School of Medical ScienceGriffith University Gold Coast CampusSouthportAustralia

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