Targeting the Mitochondrial Electron Transport Chain Complexes for the Induction of Apoptosis and Cancer Treatment

Jakub      Rohlena; Lan-feng      Dong; Jiri      Neuzil

Abstract

Treatment of cancer is by no means universally successful and often manifests harmful side effects. The best way to improve the success rate and reduce the side effects would be to develop compounds that are able to kill cancer cells while leaving normal cells unaffected. In this respect, mitocans (an acronym from ‘mitochondria’ and ‘cancer’), a summary term we proposed for compounds that induce cell death by targeting mitochondria, show an encouraging trend. Here we provide an overview of mitocans specific for the mitochondrial electron transport chain. These mitocans are particularly interesting, because a frequent consequence of electron transport chain inhibition is the induction of superoxide formation resulting in the preferential killing of cancer cells, as these tend to be more sensitive than normal cells to sudden increases in oxidative stress. Furthermore, macromolecular complexes of the electron transport chain only rarely mutate in cancer, and represent useful targets for anti-cancer drug development when widely-applicable agents are sought.

Keywords: Cancer; mitochondria, electron transport chain, oxidative stress, cancer, anti-cancer drug development, tricarboxylic acid cycle (TCA), ROS formation, target specific regulatory proteins/pathways, chronic myeloid leukemia