Anticancer Drugs Targeting the Mitochondrial Electron Transport Chain
Publication: Antioxidants & Redox Signaling
Volume 15, Issue Number 12
Abstract
Significance: Mitochondria are emerging as highly intriguing organelles showing promise but that are yet to be fully exploited as targets for anticancer drugs. Recent Advances: A group of compounds that induce mitochondrial destabilization, thereby affecting the physiology of cancer cells, has been defined and termed ‘mitocans.' Based on their mode of action of targeting in and around mitochondria, we have placed these agents into several groups including hexokinase inhibitors, compounds targeting Bcl-2 family proteins, thiol redox inhibitors, VDAC/ANT targeting drugs, electron transport chain-targeting drugs, lipophilic cations targeting the inner membrane, agents affecting the tricarboxylic acid cycle, drugs targeting mtDNA, and agents targeting other presently unknown sites. Critical Issues: Mitocans have a potential to prove highly efficient in suppressing various malignant diseases in a selective manner. They include compounds that are currently in clinical trial and offer substantial promise to become clinically applied drugs. Here we update and redefine the individual classes of mitocans, providing examples of the various members of these groups with a particular focus on agents targeting the electron transport chain, and indicate their potential application in clinical practice. Future Directions: Even though reactive oxygen species induction is important for the anticancer activity of many mitocans, the precise sequence of events preceding and following this pivotal event are not yet fully clarified, and warrant further investigation. This is imperative for effective deployment of these compounds in the clinic. Antioxid. Redox Signal. 15, 2951–2974.
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Published In
Antioxidants & Redox Signaling
Volume 15 • Issue Number 12 • December 15, 2011
Pages: 2951 - 2974
PubMed: 21777145
Copyright
Copyright 2011, Mary Ann Liebert, Inc.
History
Published in print: December 15, 2011
Published online: 31 October 2011
Published ahead of print: 1 September 2011
Published ahead of production: 21 July 2011
Accepted: 21 July 2011
Revision received: 1 July 2011
Received: 13 March 2011
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