Nitric Oxide Molecule and Human Cancers

Nitric Oxide (NO) is a short-lived, endogenously produced free radical that is synthesized by the enzyme nitric oxide synthase conversion during arginine to citrulline and serves as a key signalling molecule in various physiological and pathophysiological processes. On the other hand, excessive and unregulated NO synthesis has been implicated as a causal or contributing factor to pathophysiological conditions including cancer. NO has been suggested to modulate different cancer-related events and several lines of research have indicated that NO may have dual effects in cancer i.e. cytoprotective as well as tumour promoting. NO seems to promote tumour growth and proliferation. In contrast, NO is said to have tumoricidal properties and is being investigated for therapeutic purposes. Peroxynitrite, the product of NO and superoxide is potent oxidising agent which is the main product that mediates tissue and cell injury. Peroxynitrite is highly reactive with bio-molecules like amino acids, nucleic acids, proteins, bases and metal containing compounds. NO has been reported to exert dichotomous effects within the multistage model of cancer. It modulates different cancer-related events including angiogenesis, cell cycle, apoptosis, invasion, and metastasis. Understanding its role in tumour biology will help in developing novel NO used treatment which will provide the useful information in preventing and treating various cancers. The effects of NO in tumour biology are quite broad, spanning its involvement in formation of neoplastic lesions, cellular transformation, regulation and initiation of the metastatic lesion. NO plays an important role in tumour progression by regulation of angiogenesis. Endogenous NO promotes tumour blood flow via dilatation of arteriolar vessels. It decreases leukocyte endothelial adhesive interactions and increases vascular permeability. The understanding of different actions of NO in these cancers at the molecular level and cellular level can help in identification of NO used prognostic and diagnostic markers and also in devising potential strategies for treatment, prevention and control of cancers.