Recent Developments in the Mechanism of Anticancer Agents Based on Electron Transfer, Reactive Oxygen Species and Oxidative Stress

Peter      Kovacic; Ratnasamy      Somanathan

Abstract

Extensive evidence supports involvement of electron transfer (ET), reactive oxygen species (ROS) and oxidative stress (OS) in the mechanism of many anticancer drugs. The common ET functionalities, usually present in the drug metabolites, are quinones (or precursors), metal complexes (or complexors), hydroxylamine and nitroso from ArNO2 or ArNH2, and conjugated imines (or iminium species). The ET agents function catalytically in redox cycling with formation of ROS from oxygen. Electrochemical data add support to the mechanistic viewpoint. The generated metabolites generally possess reduction potentials amenable to ET in vivo, thus giving rise to ROS. The resulting OS is a participant in destruction of the cancer cell. The action has been termed phagomimetic based on similarity to phagocytosis. It is important to recognize that drug action is often multipronged. The various modes of action are summarized.

Keywords: Anticancer, electron transfer, reactive oxygen species, oxidative stress, ArNO2 or ArNH2, physiological responsive range, exogenous AOs, chemotherapy, mutagenic effects, transformation