title: Nitric oxide and cancer: the emerging role of S-nitrosylation.
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.
authors.affiliation: Oncology Department and Research Unit, Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Reina Sofía, Universidad de Córdoba, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Aranda
authors.forename: C
authors.initials: C
authors.lastname: López-Pedrera
authors.forename: J R
authors.initials: JR
authors.lastname: De La Haba-Rodriguez
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez-Ariza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D017209:Apoptosis; D003545:Cysteine / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D003545:Cysteine