Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin

Semin Cancer Biol. 2005 Aug;15(4):277-89. doi: 10.1016/j.semcancer.2005.04.004.


Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid l-arginine. iNOS-derived NO plays an important role in numerous physiological (e.g. blood pressure regulation, wound repair and host defence mechanisms) and pathophysiological (inflammation, infection, neoplastic diseases, liver cirrhosis, diabetes) conditions. iNOS is the synthase isoform most commonly associated with malignant disease. Nevertheless, the role of iNOS during tumor development is highly complex, and incompletely understood. Both promoting and deterring actions have been described, presumably depending upon the local concentration of iNOS within the tumor microenvironment. In particular, pivotal effects such as malingnant transformation, angiogenesis, and metastasis are modulated by iNOS. On the other hand, NO derived from macrophages has a potentially cytotoxic/cytostatic effect upon tumor cells. Hence, therapeutical interference with iNOS activity is of considerable interest, especially in tumors where metastatic activity, host defence mechanisms and the level of differentiation seem to be correlated to iNOS expression. This review will aim to summarize the dual actions of iNOS as simultaneous tumor promoter and suppressor.

Publication types

  • Review

MeSH terms

  • Gene Expression Regulation, Enzymologic
  • Humans
  • Neoplasms / enzymology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / physiology*
  • Nitric Oxide Synthase Type II


  • Nitric Oxide
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II