{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:15:32Z","timestamp":1790079332580,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hypoxia (HPX) is a significant pathological factor that contributes to mitochondrial dysfunction, oxidative stress, inflammation, and calcium dysregulation in laryngeal squamous cell carcinoma (LSCC). The redox\u2010sensitive TRPM2 channel is crucial for mediating HPX\u2010induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    excess and subsequent cell death. This study investigated whether sinapic acid (SPA), a natural phenolic compound with known antioxidant and anti\u2010inflammatory properties, can protect Hep\u20102 cells from HPX\u2010induced injury by modulating TRPM2 activity. Hep\u20102 cells were exposed to CoCl\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced HPX and treated with SPA (10\u2013150\u2009\u03bcM). Cell viability, oxidative stress parameters (malondialdehyde [MDA], glutathione [GSH], and reactive oxygen species [ROS]), intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels, mitochondrial membrane potential, and pro\u2010inflammatory cytokines (IL\u20101\u03b2 and TNF\u2010\u03b1), TRPM2 expression, and PI\u2010positive cell death were evaluated. HPX markedly decreased cell viability and increased oxidative and inflammatory responses, mitochondrial depolarization, and TRPM2\u2010dependent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx. SPA significantly restored GSH levels, reduced MDA and ROS accumulation, suppressed cytokine production, and stabilized mitochondrial membrane potential. Moreover, SPA attenuated TRPM2 upregulation and effectively lowered Ca\n                    <jats:sup>2+<\/jats:sup>\n                    overload. Co\u2010treatment with the widely used TRPM2 channel inhibitor 2\u2010APB further enhanced SPA's protective effects and produced the greatest reduction in cell death. These findings demonstrate that SPA mitigates HPX\u2010induced cytotoxicity through antioxidative, anti\u2010inflammatory, and TRPM2\u2010modulating mechanisms, highlighting its potential therapeutic relevance in LSCC.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70977","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T12:28:27Z","timestamp":1782390507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sinapic Acid Reduces Hypoxia\u2010Induced Cell Damage in Hep\u20102 Cells by Regulating TRPM2 Channel Activation"],"prefix":"10.1002","volume":"40","author":[{"given":"Halil \u0130brahim","family":"Alt\u0131ner","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine Bilecik Seyh Edebali University  Bilecik T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tar\u0131k","family":"Ya\u011fc\u0131","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Faculty of Medicine Bilecik Seyh Edebali University  Bilecik T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramazan","family":"\u00c7\u0131nar","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine Bilecik Seyh Edebali University  Bilecik T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6585-4010","authenticated-orcid":false,"given":"Kenan","family":"Y\u0131ld\u0131zhan","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine Van Yuzuncu Yil University  Van 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