Nitric Oxide and Cancer: The Emerging Role of S-Nitrosylation

Nitric oxide (NO center dot) is a short-lived, endogenously produced gas that is highly diffusible across cell membranes and acts as a signaling molecule in the body. The redox state and chemistry of NO center dot facilitate its interaction with various proteins thus regulating various intracellular and intercellular events. One of the key mechanisms by which NO center dot regulates the function of various target proteins is through the coupling of a nitroso moiety from NO-derived metabolites to a reactive cysteine leading to the formation of a S-nitrosothiol (SNO), a process commonly known as S-nitrosylation. S-nitrosylation signaling events within the cell have led to the discovery of many other physiological functions of NO center dot in many other types of cells including cancer cells. Only recently are the diverse roles of S-nitrosylation in cancer beginning to be understood. In the present review we discuss the recent evidence for the diverse roles of NO center dot/SNO-related mechanisms in cancer biology and therapy, including the participation of NO center dot in the pathogenesis of cancer, its duality in protecting against or inducing cancer cell death and the contribution of NO center dot to metastatic processes. In addition, NO center dot can be therapeutically used in the reversal of tumor cell resistance to cytotoxic drugs and as a sensitizing agent to chemo-and radiotherapy. Finally, recent studies providing evidence for NO-related mechanisms of epigenetic gene expression regulation will also be discussed. Undoubtedly, new exciting results will contribute to this rapidly expanding area of cancer research.