The Role of Nitric Oxide in Cancer: Master Regulator or NOt?
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 arre...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9393 |
| _version_ | 1797545184495403008 |
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| author | Faizan H. Khan Eoin Dervan Dibyangana D. Bhattacharyya Jake D. McAuliffe Katrina M. Miranda Sharon A. Glynn |
| author_facet | Faizan H. Khan Eoin Dervan Dibyangana D. Bhattacharyya Jake D. McAuliffe Katrina M. Miranda Sharon A. Glynn |
| author_sort | Faizan H. Khan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:11:51Z |
| format | Article |
| id | doaj.art-8c6ff8912c394550a68ceb7b35f126ba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:11:51Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8c6ff8912c394550a68ceb7b35f126ba2023-11-21T00:09:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124939310.3390/ijms21249393The Role of Nitric Oxide in Cancer: Master Regulator or NOt?Faizan H. Khan0Eoin Dervan1Dibyangana D. Bhattacharyya2Jake D. McAuliffe3Katrina M. Miranda4Sharon A. Glynn5Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway (NUIG), H91 YR71 Galway, IrelandDiscipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway (NUIG), H91 YR71 Galway, IrelandDiscipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway (NUIG), H91 YR71 Galway, IrelandDiscipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway (NUIG), H91 YR71 Galway, IrelandDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USADiscipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway (NUIG), H91 YR71 Galway, IrelandNitric 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.https://www.mdpi.com/1422-0067/21/24/9393nitric oxidenitric oxide synthasetumourigenesisDNA damage repairangiogenesisepithelial to mesenchymal transition |
| spellingShingle | Faizan H. Khan Eoin Dervan Dibyangana D. Bhattacharyya Jake D. McAuliffe Katrina M. Miranda Sharon A. Glynn The Role of Nitric Oxide in Cancer: Master Regulator or NOt? International Journal of Molecular Sciences nitric oxide nitric oxide synthase tumourigenesis DNA damage repair angiogenesis epithelial to mesenchymal transition |
| title | The Role of Nitric Oxide in Cancer: Master Regulator or NOt? |
| title_full | The Role of Nitric Oxide in Cancer: Master Regulator or NOt? |
| title_fullStr | The Role of Nitric Oxide in Cancer: Master Regulator or NOt? |
| title_full_unstemmed | The Role of Nitric Oxide in Cancer: Master Regulator or NOt? |
| title_short | The Role of Nitric Oxide in Cancer: Master Regulator or NOt? |
| title_sort | role of nitric oxide in cancer master regulator or not |
| topic | nitric oxide nitric oxide synthase tumourigenesis DNA damage repair angiogenesis epithelial to mesenchymal transition |
| url | https://www.mdpi.com/1422-0067/21/24/9393 |
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