Deciphering The Complex Biological Interactions Of Nitric Oxide In Cancer.
NO•is a free radical and is involved in a number of critical physiological processes including vasodilation, neurotransmission, immune regulation and inflammation. There are convincing evidence suggesting a role of NO•in the development and progression of different cancer types. However, the role of NO•in tumorigenesis is highly complex and both pro- and anti-neoplastic functions have been reported, which largely depends on the amount of NO•, cell types, cellular microenvironment, its interaction with other reactive species and presence of metals. An interesting interaction occurs between NO•and p53 tumor suppressor, in which NO•-induced DNA damage causes the stabilization and accumulation of p53, which in turn, transrepresses inducible nitric oxide synthase (NOS2) in a negative feedback loop. In chronic inflammatory diseases, for example ulcerative colitis, NO•induces p53 stabilization and the initiation of DNA-damage response pathway, and also generation of p53 mutation and subsequent clonal selection of p53 mutant cells. Genetic deletion of NOS2 in p53-deficient mice can either suppress or enhance lymphomagenesis depending on the inflammatory microenvironment. These findings highlight the importance of understanding the complex biological interaction of NO•in the context of the molecular makeup of each individual cancer to design NO•-targeted treatment strategies.
Pancreatic Cancer Unit, Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, USA.
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Perwez Hussain
D000818:Animals; D003226:Congresses as Topic; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D013030:Spain
D009569:Nitric Oxide