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

Autor(es)

Goncalves, Diego Assis ^{[1, 2]} ; Jasiulionis, Miriam Galvonas ^[3] ; Melo, Fabiana Henriques Machado de ^{[4, 5]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Microimuno Parasitol Dept, BR-04023062 Sao Paulo - Brazil

^[2] Univ Fed Juiz de Fora, Dept Parasitol Microbiol & Immunol, BR-36036900 Juiz De Fora - Brazil

^[3] Univ Fed Sao Paulo, Pharmacol Dept, BR-04023062 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508000 Sao Paulo - Brazil

^[5] Inst Med Assistance Publ Servants State IAMSPE, BR-04039000 Sao Paulo - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 17 SEP 2021.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 19/27517-0 - Contribuição da enzima sepiapterina redutase ao longo do desenvolvimento do melanoma
• Beneficiário: Fabiana Henriques Machado de Melo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/12306-1 - Mecanismos epigenéticos como mediadores da transformação maligna de melanócitos associada a condições sustentadas de estresse
• Beneficiário: Miriam Galvonas Jasiulionis
• Modalidade de apoio: Auxílio à Pesquisa - Regular