title: Recent developments in the mechanism of anticancer agents based on electron transfer, reactive oxygen species and oxidative stress.
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.
authors.affiliation: Department of Chemistry & Biochemistry, San Diego State University, San Diego, CA 92182-1030, USA. pkovacic@sundown.sdsu.edu
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacic
authors.forename: Ratnasamy
authors.initials: R
authors.lastname: Somanathan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology; D004579:Electron Transport; D006801:Humans; D006898:Hydroxylamines / Q000737:chemistry / Q000494:pharmacology; D007097:Imines / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009603:Nitroso Compounds / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D006898:Hydroxylamines; D007097:Imines; D009603:Nitroso Compounds; D011809:Quinones; D017382:Reactive Oxygen Species