biostudies-literatureUnknown27(4)Debsharma SScience and Engineering Research BoardGastric 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 toiScience109384https://www.ebi.ac.uk/biostudies/studies/S-EPMC10972828biostudies-literatureNSAID targets SIRT3 to trigger mitochondrial dysfunction and gastric cancer cell death.PMC10972828Saha DPal UDas TBindu SBanerjee CDe RDebsharma SMazumder SGhosh ZPramanik SChandra Maiti NBandyopadhyay UNag SfalseNSAID targets SIRT3 to trigger mitochondrial dysfunction and gastric cancer cell death.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 to2024-01-01T00:00:00Z2024 Apr2026-07-16T04:12:58.502Z2025-04-05T23:18:04.874ZS-EPMC109728283855098110.1016/j.isci.2024.109384