Definition: Inducible nitric oxide synthetase (iNOS) is an enzyme responsible for the production of the free radical nitric oxide.
Among the three isoforms of NOS that are present in various human tissues, eNOS and nNOS are calcium dependent endogenous enzymes and produce significantly low levels of NO compared to the calcium independent inducible form iNOS.
Nitric oxide (NO) is a small endogenous ubiquitously present signaling molecule with a diverse array of physiological activities that include regulation of blood flow, immunity, inflammation, and cell survival. It has been implicated in the maintenance of malignant phenotype of many cancer types.
NO is synthesized from L-Arginine by nitric oxide synthases (NOS).
Pathology
Elevated iNOS expression/activity has been reported in cancers of colon, oral, esophagus and lung.
In vitro studies using iNOS inhibitors, s-methylisothiourea (SMT) and aminoguanidine (AMG), have demonstrated that inhibition of NO production induced apoptotic pathways mediated via caspase-1/3, and PARP cleavage.
Furthermore poor survival rates have been reported in patients expressing high levels of iNOS protein. Currently available iNOS inhibitors are non-specific and lack potency.
Recent studies have implicated iNOS as an important therapeutic target to prevent melanoma.