The role of nitric oxide in cancer: Master regulator or not?

Faizan H. Khan, Eoin Dervan, Dibyangana D. Bhattacharyya, Jake D. McAuliffe, Katrina M. Miranda, Sharon A. Glynn

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

Nitric oxide (NO) is a key player in both the development and suppression of tumourigenesis depending on the source and concentration of NO. In this review, we discuss the mechanisms by which NO induces DNA damage, influences the DNA damage repair response, and subsequently modulates cell cycle arrest. In some circumstances, NO induces cell cycle arrest and apoptosis protecting against tumourigenesis. NO in other scenarios can cause a delay in cell cycle progression, allowing for aberrant DNA repair that promotes the accumulation of mutations and tumour heterogeneity. Within the tumour microenvironment, low to moderate levels of NO derived from tumour and endothelial cells can activate angiogenesis and epithelial-to-mesenchymal transition, promoting an aggressive phenotype. In contrast, high levels of NO derived from inducible nitric oxide synthase (iNOS) expressing M1 and Th1 polarised macrophages and lymphocytes may exert an anti-tumour effect protecting against cancer. It is important to note that the existing evidence on immunomodulation is mainly based on murine iNOS studies which produce higher fluxes of NO than human iNOS. Finally, we discuss different strategies to target NO related pathways therapeutically. Collectively, we present a picture of NO as a master regulator of cancer development and progression.

Original languageEnglish (US)
Article number9393
Pages (from-to)1-30
Number of pages30
JournalInternational journal of molecular sciences
Volume21
Issue number24
DOIs
StatePublished - Dec 2 2020

Keywords

  • Angiogenesis
  • Apoptosis
  • Cell cycle
  • DNA damage repair
  • Epithelial to mesenchymal transition
  • Immunomodulation
  • Nitric oxide
  • Nitric oxide synthase
  • Therapeutic target
  • Tumourigenesis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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