ArticleCancer research2013
Hepatocarcinogenesis driven by GSNOR deficiency is prevented by iNOS inhibition.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Pharmacologic Inhibition of S-Nitrosoglutathione Reductase Prevents Hyperoxic Alveolar and Airway Disease in Newborn Mice.Biomedicines · 2025Article
- Nitric oxide‑mediated S‑Nitrosylation contributes to signaling transduction in human physiological and pathological status (Review).International journal of molecular medicine · 2025Review
- The evolution of S-nitrosylation detection methodology and the role of protein S-nitrosylation in various cancers.Cancer cell international · 2024Review
- Supersulfide catalysis for nitric oxide and aldehyde metabolism.Science advances · 2023Article
- Tumor-Associated Inflammation: The Tumor-Promoting Immunity in the Early Stages of Tumorigenesis.Journal of immunology research · 2022Review
- Pillars and Gaps of S-Nitrosylation-Dependent Epigenetic Regulation in Physiology and Cancer.Life (Basel, Switzerland) · 2021Review
- ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.Cell reports · 2021Article
- Nitrosative Stress and Human Disease: Therapeutic Potential of Denitrosylation.International journal of molecular sciences · 2021Review
- S-Nitrosylation in Tumor Microenvironment.International journal of molecular sciences · 2021Review
- β-Cyclodextrin modified Pt(II) metallacycle-based supramolecular hyperbranched polymer assemblies for DOX delivery to liver cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Shank3 mutation in a mouse model of autism leads to changes in the S-nitroso-proteome and affects key proteins involved in vesicle release and synaptic function.Molecular psychiatry · 2020Article
- Hepatocellular Protein Arginine Methyltransferase 1 Suppresses Alcohol-Induced Hepatocellular Carcinoma Formation by Inhibition of Inducible Nitric Oxide Synthase.Hepatology communications · 2020Article
- Protein S-Nitrosylation: Determinants of Specificity and Enzymatic Regulation of S-Nitrosothiol-Based Signaling.Antioxidants & redox signaling · 2019Review
- Role, Targets and Regulation of (de)nitrosylation in Malignancy.Frontiers in oncology · 2018Article
- Increased GSNOR Expression during Aging Impairs Cognitive Function and Decreases S-Nitrosation of CaMKIIα.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- The role of S-nitrosoglutathione reductase (GSNOR) in human disease and therapy.Critical reviews in biochemistry and molecular biology · 2017Review
- Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats.Protoplasma · 2017Article
- S-Nitrosation of Conserved Cysteines Modulates Activity and Stability of S-Nitrosoglutathione Reductase (GSNOR).Biochemistry · 2016Article
- Nitric oxide in liver diseases.Trends in pharmacological sciences · 2015Review
- S-Nitrosoglutathione Reductase Deficiency Enhances the Proliferative Expansion of Adult Heart Progenitors and Myocytes Post Myocardial Infarction.Journal of the American Heart Association · 2015Article
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Authors and funding
4 authors.
Funding
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and deadly human cancers and it remains poorly managed. Human HCC development is often associated both with elevated expression of inducible nitric oxide synthase (iNOS) and with genetic deletion of the major denitrosylase S-nitrosoglutathione reductase (GSNOR/ADH5). However, their causal involvement in human HCC is not established. In mice, GSNOR deficiency causes S-nitrosylation and depletion of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (AGT) and increases rates of both spontaneous and DEN carcinogen-induced HCC. Here, we report that administration of 1400W, a potent and highly selective inhibitor of iNOS, blocked AGT depletion and rescued the repair of mutagenic O6-ethyldeoxyguanosines following DEN challenge in livers of GSNOR-deficient (GSNOR(-/-)) mice. Notably, short-term iNOS inhibition following DEN treatment had little effect on carcinogenesis in wild-type mice, but was sufficient to reduce HCC multiplicity, maximal size, and burden in GSNOR(-/-) mice to levels comparable with wild-type controls. Furthermore, increased HCC susceptibility in GSNOR(-/-) mice was not associated with an increase in interleukin 6, tumor necrosis factor-α, oxidative stress, or hepatocellular proliferation. These results suggested that GSNOR deficiency linked to defective DNA damage repair likely acts at the tumor initiation stage to promote HCC carcinogenesis. Together, our findings provide the first proof of principle that HCC development in the context of uncontrolled nitrosative stress can be blocked by pharmacologic inhibition of iNOS, possibly providing an effective therapy for patients with HCC.
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Registered trials
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