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The transient receptor potential (TRP) melastatin 2 (TRPM2) stimulator action of BoNT was reported in glioblastoma cells, but not in colorectal cancer (HT29) cells. By activating TRPM2, we evaluated the impacts of BoNT and oxaliplatin (OXA) incubations on oxidant and apoptotic values within the HT29 cells. Control, BoNT (5\u2009IU for 24\u2009h), OXA (50\u2009\u03bcM for 24\u2009h) and their combinations were induced. We found that TRPM2 protein is upregulated and mediates enhanced BoNT and OXA\u2010induced Ca<jats:sup>2+<\/jats:sup> entry in cells as compared to control cells. The increase of free reactive oxygen species (ROS), but the decrease of glutathione is the main ROS responsible for TRPM2 activation on H29 exposure to oxidative stress. BoNT and OXA\u2010mediated Ca<jats:sup>2+<\/jats:sup> entry through TRPM2 stimulation in response to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> results in mitochondrial Ca<jats:sup>2+<\/jats:sup> overload, followed by mitochondrial membrane depolarization, apoptosis and caspase\u20103\/\u20108\/\u20109, although they were diminished in the TRPM2 antagonist groups (<jats:italic>N<\/jats:italic>\u2010(<jats:italic>p<\/jats:italic>\u2010amylcinnamoyl)anthranilic acid and carvacrol). In conclusion, by increasing the susceptibility of HT29 tumour cells to oxidative stress and apoptosis, the combined administration of BoNT and OXA via the targeting of TRPM2 may offer a different approach to kill the tumour cells.<\/jats:p>","DOI":"10.1111\/1440-1681.13844","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:05:20Z","timestamp":1707869120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synergic actions of botulinum neurotoxin A and oxaliplatin on colorectal tumour cell death through the upregulation of <scp>TRPM2<\/scp> channel\u2010mediated oxidative stress"],"prefix":"10.1111","volume":"51","author":[{"given":"S\u0131d\u0131ka","family":"Demir","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, School of Medicine Necmettin Erbakan University  Konya 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