Title: Nitric Oxide and Cancer: The Emerging Role of S-Nitrosylation
Volume: 12
Issue: 1
Author(s): E. Aranda, C. Lopez-Pedrera, J. R. De La Haba-Rodriguez and A. Rodriguez-Ariza
Affiliation:
Keywords:
Angiogenesis, apoptosis, cancer, epigenetics, nitric oxide, S-nitrosylation, therapy, atmospheric pollutant, vasodilation, platelet aggregation, neurotransmission, antimicrobial activity, isoforms, atherosclerosis, degenerative neuronal diseases
Abstract: Nitric oxide (NO˙) 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˙ facilitate its interaction with various proteins thus regulating various intracellular and intercellular events. One of the key mechanisms by which NO˙ 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˙ 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˙/SNO-related mechanisms in cancer biology and therapy, including the participation of NO˙ in the pathogenesis of cancer, its duality in protecting against or inducing cancer cell death and the contribution of NO˙ to metastatic processes. In addition, NO˙ 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.
