ArticleAntioxidants & redox signaling2013
Targeting nitric oxide signaling with nNOS inhibitors as a novel strategy for the therapy and prevention of human melanoma.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 59 citations in OpenAlex.
- S-nitrosylation topology in melanoma: established mechanisms, unresolved redox-immune links, and a testable framework.Redox biology · 2026Review
- Enhancement of Potency and Selectivity of 2-Aminoquinoline-Based Human Neuronal Nitric Oxide Synthase Inhibitors.Journal of medicinal chemistry · 2026Article
- New Inhibitors of Neuronal Nitric Oxide Synthase for the Treatment of Melanoma.Journal of medicinal chemistry · 2026Article
- Potent, Selective, and Brain Penetrant Ether-Linked 2-Aminopyridine Inhibitors of Human Neuronal Nitric Oxide Synthase with Excellent Oral Bioavailability.Journal of medicinal chemistry · 2026Article
- S-nitrosylation of IRF7 induced by NOS1 expression in melanoma suppresses anti-tumor immunity.Cell death & disease · 2026Article
- Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors.Pharmaceutics · 2025Article
- Crosstalk Between nNOS/NO and COX-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression.Cancers · 2025Article
- Spin Trapping of Nitric Oxide by Hemoglobin and Ferrous Diethyldithiocarbamate in Model Tumors Differing in Vascularization.International journal of molecular sciences · 2024Article
- Stigmasterol Exerts an Anti-Melanoma Property through Down-Regulation of Reactive Oxygen Species and Programmed Cell Death Ligand 1 in Melanoma Cells.Antioxidants (Basel, Switzerland) · 2024Article
- ARL-17477 is a dual inhibitor of NOS1 and the autophagic-lysosomal system that prevents tumor growth in vitro and in vivo.Scientific reports · 2023Article
- Article
- Impairment of SK-MEL-28 Development-A Human Melanoma Cell Line-By theInternational journal of molecular sciences · 2023Article
- Improved synthesis and anticancer activity of a potent neuronal nitric oxide synthase inhibitor.Bioorganic & medicinal chemistry letters · 2023Article
- A Small Peptide Increases Drug Delivery in Human Melanoma Cells.Pharmaceutics · 2022Article
- The Double-Edged Sword of Oxidative Stress in Skin Damage and Melanoma: From Physiopathology to Therapeutical Approaches.Antioxidants (Basel, Switzerland) · 2022Review
- Review
- Active nNOS Is Required for Grp94-Induced Antioxidant Cytoprotection: A Lesson from Myogenic to Cancer Cells.International journal of molecular sciences · 2022Article
- Redox-Related Proteins in Melanoma Progression.Antioxidants (Basel, Switzerland) · 2022Article
- Inhibition of interferon-gamma-stimulated melanoma progression by targeting neuronal nitric oxide synthase (nNOS).Scientific reports · 2022Article
- Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies.Antioxidants (Basel, Switzerland) · 2021Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
aimsOur previous studies have shown that nitric oxide (NO) plays an important role in increasing the invasion and proliferation of human melanoma cells, suggesting that targeting NO signaling may facilitate therapy and prevention. Neuronal nitric oxide synthase (nNOS) is present in melanocytes, a cell type that originates from the neural crest. The aims of this study were to determine the role of nNOS in melanoma progression and the potential antitumor effects of novel synthesized nNOS inhibitors.
resultsIn vitro studies demonstrated abundant expression of nNOS in melanoma compared to melanocytes, which was inducible by ultraviolet radiation and was associated with increased NO generation. nNOS was also detected in melanoma biopsies that increased with disease stage. Knockdown of nNOS in melanoma cells diminished L-arginine-induced NO production; the metastatic capacity was also reduced as well as the levels of MMP-1, Bcl-2, JunD, and APE/Ref-1. Similar inhibition of NO and invasion potential was observed utilizing novel, highly selective nNOS inhibitors. In three-dimensional human skin reconstructs, the nNOS inhibitor cpd8 effectively reversed the melanoma overgrowth stimulated by NO stress. INNOVATION: Our work lays the foundation for development of clinical "drug-like" nNOS inhibitors as a new and promising strategy for the chemoprevention of early melanoma progression and the inhibition of secondary melanoma in high-risk individuals.
conclusionBased on our observations, we propose that nNOS in melanoma results in constitutive overproduction of NO, which stimulates proliferation and increases invasion potential, leading to subsequent development of metastases.
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