Nitric oxide and cancer

Yim, Chang Yeol

Abstract

Nitric oxide (NO) is emerging as a potential anti-cancer agent to overcome tumor cell resistance to conventional therapeutic agents. NO is a short-life molecule produced from L-arginine by the nitric oxide synthase (NOS). There are three isoforms of the enzyme: neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or NOS3). Each of these isoforms may be expressed in a variety of cell types. The actions of NO are highly variable in oncology revealing both sides of the spectrum as an anti-neoplastic versus a pro-neoplastic agent. The final activity of NO is dependent on its working microenvironment, including the type of cell exposed to NO, the redox state of the reaction, as well as the final intracellular concentration and the duration of exposure to NO. NO donors mimic continuous production of NO in a wide range of time intervals (seconds to days). Thus, multiple biological and (pro- versus anti-) neoplastic responses are elicited from NO donors depending on the half-life and the type of cell exposed to the compound. This paper is a review of the current knowledge of various roles of NO in cancer.