Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human melanoma development

Gonçalves, Diego Assis; Xisto, Ricardo; Gonçalves, Jéssica; Silva, Douglas Baceti da; Soares, Jaqueline Pereira Moura; Icimoto, Marcelo Yudi; Sant’Anna, Carla; Gimenez, Marcela; Angelis, Kátia De; Llesuy, Susana; Fernandes, Denise C.; Laurindo, Francisco Rafael Martins; Jasiulionis, Miriam Galvonas; Melo, Fabiana Henriques Machado de

doi:10.1016/j.biocel.2019.105592

Cited by 13 publications

(20 citation statements)

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“…24 Another investigation revealed that IL8 is regulated by nitric oxide in melanoma cells. 25 An imbalanced relationship between nitric oxide and superoxide anion which is resulted from uncoupled nitric oxide synthase and affects human melanoma development is reported by Gonçalves et al 26 The positive regulation of norepinephrine uptake is another term that is attributed to the central nodes. There is evidence that stress hormones can promote the growth of B16-F10 melanoma metastases.…”

Section: Discussionmentioning

confidence: 95%

The Highlighted Role of GAPDH and Nitric-Oxide Synthase Regulator Activity in Proton Beam Irradiated Melanoma BLM Cells

et al. 2019

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Introduction: The human melanoma is a type of invasive tumor the treatment of which is challenging. To better understand the proton irradiation mechanisms as one of the widely applied therapy for this type of cancer, bioinformatics analysis of proteomics outcome could be beneficial. Methods: Protein-protein interaction network analysis of the differentially expressed proteins (DEPs) of melanoma BLM (BRO lung metastasis) cells in the treatment of 3 Gy dosage proton therapy was performed in this study via Cytoscape V.3.7.2. and its integrated plug-ins. Results: Eighteen DEPs were searched for network constructions and limited numbers of query +neighbor proteins were found central. The hub-bottlenecks (i.e. central nodes) were GAPDH, ACTB, ALB, AKT1, TP53, and EGFR. The fist mentioned proteins were from DEPs. The enrichment analysis of these elements identified nitric-oxide synthase regulator activity and the positive regulation of the norepinephrine uptake that may be the key to the mechanisms of proton therapy. Conclusion: In conclusion, the identified central nodes (EGFR, TP53, ALB, AKT1, GAPDH, and ACTB) and the related biological terms are the critical affected genes and biological terms in the irradiated melanoma cells.

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Section: Discussionmentioning

confidence: 95%

The Highlighted Role of GAPDH and Nitric-Oxide Synthase Regulator Activity in Proton Beam Irradiated Melanoma BLM Cells

et al. 2019

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“…Many studies have reported the dual effect of NO in cancer cells [21,26]. In melanoma cells, increased NO concentration causes growth arrest and apoptosis [13,27]. Evodiamine treatment induced p38 and NF-κB activation, which in turn triggers NO-derived iNOS, increasing apoptosis in a p53-dependent manner [28].…”

Section: Nitric Oxide Synthasementioning

confidence: 99%

“…Dysfunctional NOS is a source of superoxide anion (O 2 •− ), which is associated with the development of cardiovascular diseases, diabetes, neurodegenerative disorders, and more recently, its role in cancer has been reported [13,[35][36][37]. The role of ROS in malignant transformation and tumor progression depends on its concentration and cancer stage, contributing to carcinogenesis or tumor cell death [13,16,33].…”

Section: Nitric Oxide Synthasementioning

confidence: 99%

“…Although increased expression of the three NOS isoforms in different cancers has been related in innumerous studies, not all the studies describe NOS activity [13,[38][39][40][41]. High NOS expression is associated with increased cell proliferation, metastasis, and chemotherapy resistance, in some cases being associated with poor prognosis [26,40,42].…”

Section: Nitric Oxide Synthasementioning

confidence: 99%

“…Moreover, nitric oxide (NO) and reactive nitrogen species (RNS) metabolism are also altered in inflammation [11]. High reactive oxygen species (ROS) levels found in tumors are caused by different mechanisms, including increased NADPH oxidase expression and activity, mitochondrial damage, endoplasmic reticulum stress, and nitric oxide synthase dysfunction (NOS) [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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

Gonçalves

Jasiulionis

Melo

2021

IJMS

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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.

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The exploitation of enzyme-based cancer immunotherapy

et al. 2022

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Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human melanoma development

Cited by 13 publications

References 53 publications

The Highlighted Role of GAPDH and Nitric-Oxide Synthase Regulator Activity in Proton Beam Irradiated Melanoma BLM Cells

The Highlighted Role of GAPDH and Nitric-Oxide Synthase Regulator Activity in Proton Beam Irradiated Melanoma BLM Cells

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

The exploitation of enzyme-based cancer immunotherapy

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