Unifying mechanism for anticancer agents involving electron transfer and oxidative stress: Clinical implications

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), aromatic nitro compounds (or reduced hydroxylamine and nitroso derivatives), 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. It is important to recognize that drug action is often multipronged. The various modes of action are summarized. Most research has been devoted to development of new and improved chemotherapeutic agents. The need for more attention to measures for cancer prevention is addressed. One of the most promising involves use of antioxidants. (c) 2007 Elsevier Ltd. All rights reserved.