ArticleBritish journal of cancer2019
Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- ACE2 Expression Is Increased in the Lungs of Patients With Comorbidities Associated With Severe COVID-19.The Journal of infectious diseases · 2020Pooled it
- Site-specific programming characterizes dynamic post-translational acetylation of histone H2B lysine 108 in mouse embryonic stem cells.Nature communications · 2026Article
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- Targeted protein degradation: species, diseases and efficient utilization.Journal of translational medicine · 2025Review
- SPB-201 Alleviates Indomethacin-Induced Gastric Damage in Rats through Its Antioxidant, Anti-inflammatory, and Pro-angiogenic Properties.The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2025Article
- The hydroxamate based HDAC inhibitor WMJ-J-09 induces colorectal cancer cell death by targeting tubulin and downregulating survivin.Scientific reports · 2025Article
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- Exploring COX-Independent Pathways: A Novel Approach for Meloxicam and Other NSAIDs in Cancer and Cardiovascular Disease Treatment.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- Comprehensive analysis of the prognostic, immunological, and diagnostic roles of SIRT1 in pan-cancer and its validation in KIRC.Frontiers in immunology · 2024Article
- Fucoxanthin Abrogates Ionizing Radiation-Induced Inflammatory Responses by Modulating Sirtuin 1 in Macrophages.Marine drugs · 2023Article
- SIRT1 is an actionable target to restore p53 function in HPV-associated cancer therapy.British journal of cancer · 2023Article
- Review
- Article
- Development and Challenges of Diclofenac-Based Novel Therapeutics: Targeting Cancer and Complex Diseases.Cancers · 2022Review
- Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations.American journal of human genetics · 2022Article
- Deacetylation of Transcription Factors in Carcinogenesis.International journal of molecular sciences · 2021Review
- Current View on the Mechanisms of Alcohol-Mediated Toxicity.International journal of molecular sciences · 2021Review
- Epigenetic Mechanisms Underlying COVID-19 Pathogenesis.Biomedicines · 2021Review
- Epigenetic alterations and genetic variations of angiotensin-converting enzyme 2 (ACE2) as a functional receptor for SARS-CoV-2: potential clinical implications.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as chemopreventive agents for many tumours; however, the mechanism responsible for their anti-neoplastic activity remains elusive and the side effects due to cyclooxygenase (COX) inhibition prevent this clinical application.
methodsMolecular biology, in silico, cellular and in vivo tools, including innovative in vivo imaging and classical biochemical assays, were applied to identify and characterise the COX-independent anti-cancer mechanism of NSAIDs.
resultsHere, we show that tumour-protective functions of NSAIDs and exisulind (a sulindac metabolite lacking anti-inflammatory activity) occur through a COX-independent mechanism. We demonstrate these NSAIDs counteract carcinogen-induced proliferation by inhibiting the sirtuin 1 (SIRT1) deacetylase activity, augmenting acetylation and activity of the tumour suppressor p53 and increasing the expression of the antiproliferative gene p21. These properties are shared by all NSAIDs except for ketoprofen lacking anti-cancer properties. The clinical interest of the mechanism identified is underlined by our finding that p53 is activated in mastectomy patients undergoing intraoperative ketorolac, a treatment associated with decreased relapse risk and increased survival.
conclusionOur study, for the first-time, links NSAID chemopreventive activity with direct SIRT1 inhibition and activation of the p53/p21 anti-oncogenic pathway, suggesting a novel strategy for the design of tumour-protective drugs.
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