Nitric oxide and pH modulation in gynaecological cancer

Sanhueza, Carlos, Araos, Joaquın, Naranjo, Luciano, Barros, Eric, Subiabre, Mario, Toledo, Fernando, Gutierrez, Jaime, Chiarello, Delia I., Pardo, Fabian, Leiva, Andrea and Sobrevia, Luis (2016) Nitric oxide and pH modulation in gynaecological cancer. Journal of Cellular and Molecular Medicine, 20 12: 2223-2230. doi:10.1111/jcmm.12921

Author Sanhueza, Carlos
Araos, Joaquın
Naranjo, Luciano
Barros, Eric
Subiabre, Mario
Toledo, Fernando
Gutierrez, Jaime
Chiarello, Delia I.
Pardo, Fabian
Leiva, Andrea
Sobrevia, Luis
Title Nitric oxide and pH modulation in gynaecological cancer
Journal name Journal of Cellular and Molecular Medicine   Check publisher's open access policy
ISSN 1582-1838
Publication date 2016-12-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1111/jcmm.12921
Open Access Status DOI
Volume 20
Issue 12
Start page 2223
End page 2230
Total pages 8
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2017
Language eng
Formatted abstract
Nitric oxide plays several roles in cellular physiology, including control of the vascular tone and defence against pathogen infection. Neuronal, inducible and endothelial nitric oxide synthase (NOS) isoforms synthesize nitric oxide. Cells generate acid and base equivalents, whose physiological intracellular concentrations are kept due to membrane transport systems, including Na+/H+ exchangers and Na+/HCO3 transporters, thus maintaining a physiological pH at the intracellular (~7.0) and extracellular (~7.4) medium. In several pathologies, including cancer, cells are exposed to an extracellular acidic microenvironment, and the role for these membrane transport mechanisms in this phenomenon is likely. As altered NOS expression and activity is seen in cancer cells and because this gas promotes a glycolytic phenotype leading to extracellular acidosis in gynaecological cancer cells, a pro-inflammatory microenvironment increasing inducible NOS expression in this cell type is feasible. However, whether abnormal control of intracellular and extracellular pH by cancer cells regards with their ability to synthesize or respond to nitric oxide is unknown. We, here, discuss a potential link between pH alterations, pH controlling membrane transport systems and NOS function. We propose a potential association between inducible NOS induction and Na+/H+ exchanger expression and activity in human ovary cancer. A potentiation between nitric oxide generation and the maintenance of a low extracellular pH (i.e. acidic) is proposed to establish a sequence of events in ovarian cancer cells, thus preserving a pro-proliferative acidic tumour extracellular microenvironment. We suggest that pharmacological therapeutic targeting of Na+/H+ exchangers and inducible NOS may have benefits in human epithelial ovarian cancer.
Keyword NHE
Nitric oxide
Ovarian cancer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
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