ArticleFrontiers in oncology2023
Uncoupled nitric oxide synthase activity promotes colorectal cancer progression.
Article in Frontiers in oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Nitric oxide-driven Warburg reprogramming at the NOS2-COX2 axis: An integrative engine of cancer hallmarks.Redox biology · 2026Review
- TOP2 and NOS2 Orchestrate the Generation of DNA Breaks to Promote Colitis Cancer Initiation.Cancers · 2026Article
- RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.Frontiers in immunology · 2026Review
- Dietary nitrosyl-heme from processed meats and its association with colorectal cancer risk: findings from the EPIC cohort study.Nutrition journal · 2025Article
- Review
- Dissecting the opposing regulatory functions of endogenous nitric oxide production in colorectal cancer initiation, adaptive immune response alterations, and ferroptosis execution.Oncology reviews · 2025Review
- NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Increased levels of reactive oxygen/nitrogen species are one hallmark of chronic inflammation contributing to the activation of pro-inflammatory/proliferative pathways. In the cancers analyzed, the tetrahydrobiopterin:dihydrobiopterin ratio is lower than that of the corresponding normal tissue, leading to an uncoupled nitric oxide synthase activity and increased generation of reactive oxygen/nitrogen species. Previously, we demonstrated that prophylactic treatment with sepiapterin, a salvage pathway precursor of tetrahydrobiopterin, prevents dextran sodium sulfate-induced colitis in mice and associated azoxymethane-induced colorectal cancer. Herein, we report that increasing the tetrahydrobiopterin:dihydrobiopterin ratio and recoupling nitric oxide synthase with sepiapterin in the colon cancer cell lines, HCT116 and HT29, inhibit their proliferation and enhance cell death, in part, by Akt/GSK-3β-mediated downregulation of β-catenin. Therapeutic oral gavage with sepiapterin of mice bearing azoxymethane/dextran sodium sulfate-induced colorectal cancer decreased metabolic uptake of [
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Registered trials
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.