The dual role of iNOS in cancer

Redox Biol. 2015 Dec;6:334-343. doi: 10.1016/j.redox.2015.08.009. Epub 2015 Aug 24.


Nitric oxide (NO) is one of the 10 smallest molecules found in nature. It is a simple gaseous free radical whose predominant functions is that of a messenger through cGMP. In mammals, NO is synthesized by the enzyme nitric oxide synthase (NOS) of which there are three isoforms. Neuronal (nNOS, NOS1) and endothelial (eNOS, NOS3) are constitutive calcium-dependent forms of the enzyme that regulate neural and vascular function respectively. The third isoform (iNOS, NOS2), is calcium-independent and is inducible. In many tumors, iNOS expression is high, however, the role of iNOS during tumor development is very complex and quite perplexing, with both promoting and inhibiting actions having been described. This review will aim to summarize the dual actions of iNOS-derived NO showing that the microenvironment of the tumor is a contributing factor to these observations and ultimately to cellular outcomes.

Keywords: Apoptosis; Cancer; Cell situation; Nitric oxide; Stroma; iNOS.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Bystander Effect
  • Cyclic GMP / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Nitric Oxide Synthase Type II / genetics*
  • Nitric Oxide Synthase Type II / metabolism
  • Polymorphism, Genetic
  • Signal Transduction
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics


  • Antineoplastic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • NF-kappa B
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Cyclic GMP