The role of nitric oxide in cancer
Top Cited Papers
Open Access
- 1 December 2002
- journal article
- review article
- Published by Springer Science and Business Media LLC in Cell Research
- Vol. 12 (5-6), 311-320
- https://doi.org/10.1038/sj.cr.7290133
Abstract
Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including vasodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases (NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interestingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting the etiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and has been associated with tumour grade, proliferation rate and expression of important signaling components associated with cancer development such as the oestrogen receptor. It appears that high levels of NOS expression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumor cells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxically therefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic properties. Increased NO-generation in a cell may select mutant p53 cells and contribute to tumour angiogenesis by upregulating VEGF. In addition, NO may modulate tumour DNA repair mechanisms by upregulating p53, poly(ADP-ribose) polymerase (PARP) and the DNA-dependent protein kinase (DNA-PK). An understanding at the molecular level of the role of NO in cancer will have profound therapeutic implications for the diagnosis and treatment of disease.Keywords
This publication has 46 references indexed in Scilit:
- Deoxyribonucleic acid damage/repairproteins are elevated in the failing human myocardium due to idiopathic dilated cardiomyopathyJournal of the American College of Cardiology, 2002
- Expression of endothelial and inducible nitric oxide synthase in benign and malignant lesions of the breast and measurement of nitric oxide using electron paramagnetic resonance spectroscopyCancer, 2002
- Microencapsulated iNOS‐expressing cells cause tumor suppression in miceThe FASEB Journal, 2001
- INDUCIBLE NITRIC OXIDE SYNTHASE WITH TRANSITIONAL CELL CARCINOMA OF THE BLADDERJournal of Urology, 1999
- Suppression of Tumorigenicity and Metastasis of Human Renal Carcinoma Cells by Infection with Retroviral Vectors Harboring the Murine Inducible Nitric Oxide Synthase GeneHuman Gene Therapy, 1998
- NITRIC OXIDE AND MACROPHAGE FUNCTIONAnnual Review of Immunology, 1997
- Aberrant expression of nitric oxide synthase in human polyps, neoplastic colonic mucosa and surrounding peritumoral normal mucosaCarcinogenesis: Integrative Cancer Research, 1994
- DNA Deaminating Ability and Genotoxicity of Nitric Oxide and its ProgenitorsScience, 1991
- The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholineNature, 1980
- NITRO-GLYCERINE AS A REMEDY FOR ANGINA PECTORIS.The Lancet, 1879