Mechanisms of anti-cancer agents: Emphasis on oxidative stress and electron transfer

A large body of evidence has accumulated indicating involvement of oxidativ e stress (OS) in the mode of action of various bioactive substances, includ ing those of the immune system. The data for anticancer drugs (main and mis cellaneous) are summarized herein. Although diverse origins pertain, reacti ve oxygen species (ROS) are frequently generated by redox cycling via elect ron transfer (ET) groups, such as quinones (or phenolic precursors), metal complexes (or complexors), aromatic nitro compounds (or reduced products) a nd conjugated imines (or iminium species). We believe it is not coincidenta l that these functionalities are frequently found in anticancer agents or t heir metabolites. Generally, the ET moieties display reduction potentials i n the physiologically active range. Often ROS are also implicated in more t raditional rationales, namely, enzyme inhibition, membrane or DNA insult, a nd interference with DNA or protein synthesis. A multi-faceted approach to mechanism appears to be the most logical. Significantly, the unifying theme of ET-OS also applies to other drug categories, as well as to toxins, carc inogens, hormones, and enzymes. Since this theoretical framework aids in ou r understanding of drug action, it can serve as a useful tool in the design of more active and safer pharmaceuticals.