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The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin

1
Micro-Imuno-Parasitology Department, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil
2
Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, Juiz de Fora 36036-900, Brazil
3
Pharmacology Department, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil
4
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo 05508-000, Brazil
5
Institute of Medical Assistance to Public Servants of the State (IAMSPE), São Paulo 04039-000, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Tzong-Shyuan Lee
Int. J. Mol. Sci. 2021, 22(17), 9546; https://doi.org/10.3390/ijms22179546
Received: 1 August 2021 / Revised: 22 August 2021 / Accepted: 23 August 2021 / Published: 2 September 2021
(This article belongs to the Special Issue Nitric Oxide Synthases: Regulation and Function 2021)
Cancer development is associated with abnormal proliferation, genetic instability, cell death resistance, metabolic reprogramming, immunity evasion, and metastasis. These alterations are triggered by genetic and epigenetic alterations in genes that control cell homeostasis. Increased reactive oxygen and nitrogen species (ROS, RNS) induced by different enzymes and reactions with distinct molecules contribute to malignant transformation and tumor progression by modifying DNA, proteins, and lipids, altering their activities. Nitric oxide synthase plays a central role in oncogenic signaling modulation and redox landscape. Overexpression of the three NOS isoforms has been found in innumerous types of cancer contributing to tumor growth and development. Although the main function of NOS is the production of nitric oxide (NO), it can be a source of ROS in some pathological conditions. Decreased tetrahydrobiopterin (BH4) cofactor availability is involved in NOS dysfunction, leading to ROS production and reduced levels of NO. The regulation of NOSs by BH4 in cancer is controversial since BH4 has been reported as a pro-tumoral or an antitumoral molecule. Therefore, in this review, the role of BH4 in the control of NOS activity and its involvement in the capabilities acquired along tumor progression of different cancers was described. View Full-Text
Keywords: cancer; nitric oxide synthase; tetrahydrobiopterin; sepiapterin cancer; nitric oxide synthase; tetrahydrobiopterin; sepiapterin
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MDPI and ACS Style

Gonçalves, D.A.; Jasiulionis, M.G.; Melo, F.H.M.d. The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin. Int. J. Mol. Sci. 2021, 22, 9546. https://doi.org/10.3390/ijms22179546

AMA Style

Gonçalves DA, Jasiulionis MG, Melo FHMd. The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin. International Journal of Molecular Sciences. 2021; 22(17):9546. https://doi.org/10.3390/ijms22179546

Chicago/Turabian Style

Gonçalves, Diego A., Miriam G. Jasiulionis, and Fabiana H.M.d. Melo. 2021. "The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin" International Journal of Molecular Sciences 22, no. 17: 9546. https://doi.org/10.3390/ijms22179546

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