ArticleMolecular cancer research : MCR2015
The Role of Nitric Oxide Synthase Uncoupling in Tumor Progression.
Article in Molecular cancer research : MCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
- Targeting endoplasmic reticulum stress and nitroso-redox imbalance in neuroendocrine prostate cancer: the therapeutic role of nitric oxide.Cell death discovery · 2025Article
- Immunogenic shift of arginine metabolism triggers systemic metabolic and immunological reprogramming to suppress HER2 + breast cancer.Cancer & metabolism · 2025Article
- Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism.Life science alliance · 2024Article
- In Vitro Cytotoxic Potential and In Vivo Antitumor Effects of NOS/PDK-Inhibitor T1084.International journal of molecular sciences · 2024Article
- Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism.bioRxiv : the preprint server for biology · 2023Article
- Biopterin metabolism and nitric oxide recoupling in cancer.Frontiers in oncology · 2023Review
- Uncoupled nitric oxide synthase activity promotes colorectal cancer progression.Frontiers in oncology · 2023Article
- S-nitrosylation of CSF1 receptor increases the efficacy of CSF1R blockage against prostate cancer.Cell death & disease · 2022Article
- Disruption of Redox Homeostasis by Alterations in Nitric Oxide Synthase Activity and Tetrahydrobiopterin along with Melanoma Progression.International journal of molecular sciences · 2022Article
- Combination of NOS- and PDK-Inhibitory Activity: Possible Way to Enhance Antitumor Effects.International journal of molecular sciences · 2022Article
- mGWAS identification of six novel single nucleotide polymorphism loci with strong correlation to gastric cancer.Cancer & metabolism · 2021Article
- Metastatic Melanoma Progression Is Associated with Endothelial Nitric Oxide Synthase Uncoupling Induced by Loss of eNOS:BH4 Stoichiometry.International journal of molecular sciences · 2021Article
- 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 · 2021Review
- Article
- Mitigation of Radiation-Induced Lung and Heart Injuries in Mice by Oral Sepiapterin after Irradiation.Radiation research · 2021Article
- S-Nitrosylation in Tumor Microenvironment.International journal of molecular sciences · 2021Review
- The Critical Role of Tetrahydrobiopterin (BH4) Metabolism in Modulating Radiosensitivity: BH4/NOS Axis as an Angel or a Devil.Frontiers in oncology · 2021Review
- Nebivolol combined with tetrahydrobiopterin affects diastolic function in spontaneously hypertensive rats via the nitric oxide/cyclic guanosine monophosphate signalling pathway.BMC pharmacology & toxicology · 2020Article
- Endothelial-Tumor Cell Interaction in Brain and CNS Malignancies.International journal of molecular sciences · 2020Review
- Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledHere, evidence suggests that nitric oxide synthases (NOS) of tumor cells, in contrast with normal tissues, synthesize predominantly superoxide and peroxynitrite. Based on high-performance liquid chromatography analysis, the underlying mechanism for this uncoupling is a reduced tetrahydrobiopterin:dihydrobiopterin ratio (BH4:BH2) found in breast, colorectal, epidermoid, and head and neck tumors compared with normal tissues. Increasing BH4:BH2 and reconstitution of coupled NOS activity in breast cancer cells with the BH4 salvage pathway precursor, sepiapterin, causes significant shifts in downstream signaling, including increased cGMP-dependent protein kinase (PKG) activity, decreased β-catenin expression, and TCF4 promoter activity, and reduced NF-κB promoter activity. Sepiapterin inhibited breast tumor cell growth in vitro and in vivo as measured by a clonogenic assay, Ki67 staining, and 2[18F]fluoro-2-deoxy-D-glucose-deoxyglucose positron emission tomography (FDG-PET). In summary, using diverse tumor types, it is demonstrated that the BH4:BH2 ratio is lower in tumor tissues and, as a consequence, NOS activity generates more peroxynitrite and superoxide anion than nitric oxide, resulting in important tumor growth-promoting and antiapoptotic signaling properties. IMPLICATIONS: The synthetic BH4, Kuvan, is used to elevate BH4:BH2 in some phenylketonuria patients and to treat diseases associated with endothelial dysfunction, suggesting a novel, testable approach for correcting an abnormality of tumor metabolism to control tumor growth.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.