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The role of nitric oxide in cancer
Weiming Xu1, Li Zhi Liu, Marilena Loizidou
1Wolfson Institute for Biomedical Research, Cruciform Building, Gower Street, UCL, London WC1 E 6A U, UK. w.xu@ucl.ac.uk
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), endothelia (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.
Insights
Nitric oxide (NO) plays a dual role in cancer, potentially inhibiting or promoting tumor growth depending on its levels. Understanding NO
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Nitric oxide (NO) is a key signaling molecule involved in vital physiological processes.
- The nitric oxide synthase (NOS) family includes inducible (iNOS), endothelial (eNOS), and neuronal (nNOS) isoforms.
- NOS activity is implicated in cancer development, affecting tumor grade and proliferation.
Purpose of the Study:
- To elucidate the complex and often contradictory roles of nitric oxide (NO) in cancer etiology.
- To investigate how different levels of NOS activity influence tumor progression and characteristics.
- To explore the molecular mechanisms by which NO impacts cancer cells, including DNA repair and angiogenesis.
Main Methods:
- Review of existing scientific literature on nitric oxide synthases and cancer.
- Analysis of studies reporting NOS activity in various tumor types and its correlation with clinical parameters.
- Examination of molecular pathways affected by NO, such as VEGF, p53, PARP, and DNA-PK.
Main Results:
- High NOS expression, particularly from activated macrophages, can be cytotoxic to tumor cells.
- Low-level NOS activity may paradoxically promote tumor growth and angiogenesis.
- NO influences cancer by potentially selecting for mutant p53 cells and modulating DNA repair mechanisms.
Conclusions:
- Nitric oxide exhibits pleiotropic effects in cancer, acting as both a tumor suppressor and promoter.
- Understanding the precise molecular roles of NO in cancer is crucial for developing targeted therapies.
- Further research into NO's dual function can lead to novel diagnostic and therapeutic strategies for cancer treatment.