ArticleiScience2024
NSAID targets SIRT3 to trigger mitochondrial dysfunction and gastric cancer cell death.
Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- New Functions of Mitochondrial Dysfunction in Gastric Cancer: From Molecular Processes to Potential Treatments.International journal of molecular sciences · 2026Review
- Metabolic Signaling Meets Epigenetic Regulation: How Protein Lactylation Remodels the Tumor Immune Microenvironment in Gastric Cancer.Current issues in molecular biology · 2026Review
- Proteomic and Metabolomic Profiling Reveal Mitochondrial Transplantation-Mediated Reprogramming in Gastric Cancer Cells.The Kaohsiung journal of medical sciences · 2026Article
- SIRT3 activation protects from nabumetone-induced mitochondrial toxicity in adult human cardiomyocytes.Cellular and molecular life sciences : CMLS · 2026Article
- Review
- Relevance and application of sirtuin 3-activated mitophagy in gastric cancer treatment.World journal of clinical oncology · 2025Review
- Multi-omics Analysis Implicates Mitochondrial Complex Assembly Protein COX18 in Mitochondrial Signaling and Tumorigenesis across Cancers.Cell biochemistry and biophysics · 2025Article
- Total Astragalus saponins promote ferroptosis in gastric cancer cells by upregulating SIRT3.Translational cancer research · 2025Article
- Implication of protein post translational modifications in gastric cancer.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer (GC) is a deadly malignancy that demands effective therapeutic intervention capitalizing unique drug target/s. Here, we report that indomethacin, a cyclooxygenase non-selective non-steroidal anti-inflammatory drug, arrests GC cell growth by targeting mitochondrial deacetylase Sirtuin 3 (SIRT3). Interaction study revealed that indomethacin competitively inhibited SIRT3 by binding to nicotinamide adenine dinucleotide (NAD)-binding site. The Cancer Genome Atlas data meta-analysis indicated poor prognosis associated with high SIRT3 expression in GC. Further, transcriptome sequencing data of human gastric adenocarcinoma cells revealed that indomethacin treatment severely downregulated SIRT3. Indomethacin-induced SIRT3 downregulation augmented SOD2 and OGG1 acetylation, leading to mitochondrial redox dyshomeostasis, mtDNA damage, respiratory chain failure, bioenergetic crisis, mitochondrial fragmentation, and apoptosis via blocking the AMPK/PGC1α/SIRT3 axis. Indomethacin also downregulated SIRT3 regulators ERRα and PGC1α. Further, SIRT3 knockdown aggravated indomethacin-induced mitochondrial dysfunction as well as blocked cell-cycle progression to increase cell death. Thus, we reveal how indomethacin induces GC cell death by disrupting SIRT3 signaling.
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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.