S-Nitrosothiol Metabolism In Cancer And Therapeutic Implications

The complex chemistry and biochemistry of nitric oxide (NO) and their relation to both physiological and pathological processes is one of the main reasons of the considerable difficulties in understanding the precise roles of this small molecule in cancer biology. One of the modifications mediated by NO is the coupling of a nitroso group moiety to a reactive thiol group in specific cysteine residues in peptides or proteins resulting in S-nitrosothiol (SNO) formation, a process commonly known as S-nitrosylation. In many cases, an altered production of NO and/or impaired SNO homeostasis promotes an aberrant S-nitrosylation of proteins. Importantly, this alteration in SNO homeostasis and S-nitrosylation of proteins plays an important role in a broad range of diseases, including cancer. Recent research in cell metabolism of SNOs has led to the identification and characterization of enzyme-mediated processes (nitrosylases and denitrosylases) that are implicated in targeted S-nitrosylation or denitrosylation of proteins in physiological settings. In this chapter, we will review these studies that may help to unravel the complex interrelationships between NO and the molecular pathways in the initiation and progression of tumors and their response to therapy.