{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T15:47:41Z","timestamp":1765295261941,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:00:00Z","timestamp":1634428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Melatonin is a hormone that is primarily produced in the pineal gland and is involved in wide range of biological functions. However, the impact of melatonin on chemotherapy\u2010induced cell death remains to be elucidated in oral squamous cell carcinoma (OSCC) cells. The objective of this study was to clarify the role of melatonin in cisplatin\u2010induced cytotoxicity in CD44<jats:sup>high<\/jats:sup> OSCC cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CD44<jats:sup>high<\/jats:sup> OSCC cells were cultured on fibronectin\u2010coated hydrogel. A lactate dehydrogenase cytotoxicity assay was performed to evaluate cisplatin\u2010induced cell death. The effect of melatonin on cisplatin\u2010induced cell death and Derlin\u20101 (DERL1) endoplasmic reticulum membrane protein expression was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CD44<jats:sup>high<\/jats:sup> OSCC cells exhibited mesenchymal\u2010like features when cultured on fibronectin\u2010coated hydrogel. Mesenchymal\u2010like CD44<jats:sup>high<\/jats:sup> OSCC cells demonstrated strong resistance to cisplatin\u2010induced cell death compared with epithelial\u2010like CD44<jats:sup>high<\/jats:sup> OSCC cells. <jats:italic>DERL1<\/jats:italic>\u00a0mRNA and DERL1 protein expression levels were significantly higher in mesenchymal\u2010like CD44<jats:sup>high<\/jats:sup> cells compared with epithelial\u2010like CD44<jats:sup>high<\/jats:sup> cells. Cisplatin\u2010induced cell death was significantly enhanced after <jats:italic>DERL1<\/jats:italic>\u00a0siRNA knockdown, suggesting that DERL1 is involved in resistance to cisplatin\u2010induced cell death. Melatonin significantly inhibited DERL1 expression and enhanced cisplatin\u2010induced cell death in mesenchymal\u2010like CD44<jats:sup>high<\/jats:sup> cells. <jats:italic>miR<\/jats:italic>\u2010<jats:italic>181c<\/jats:italic>\u2010<jats:italic>5p<\/jats:italic> expression was significantly upregulated in the presence of melatonin. Furthermore, melatonin\u2010inhibited DERL1 expression was significantly recovered by <jats:italic>miR<\/jats:italic>\u2010<jats:italic>181c<\/jats:italic>\u2010<jats:italic>5p<\/jats:italic> inhibitor. In addition, melatoninenhanced cisplatin\u2010induced cell death was attenuated by <jats:italic>miR<\/jats:italic>\u2010<jats:italic>181c<\/jats:italic>\u2010<jats:italic>5p<\/jats:italic> inhibitor. These results suggest that melatonin\u2010induced <jats:italic>miR<\/jats:italic>\u2010<jats:italic>181c<\/jats:italic>\u2010<jats:italic>5p<\/jats:italic> enhances cisplatin\u2010induced cell death through inhibition of DERL1 in mesenchymal\u2010like CD44<jats:sup>high<\/jats:sup> cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Melatonin plays a vital role in promoting cisplatin\u2010induced cytotoxicity in mesenchymal\u2010like CD44<jats:sup>high<\/jats:sup> OSCC cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.13242","type":"journal-article","created":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T20:19:51Z","timestamp":1632341991000},"page":"281-289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Melatonin enhances cisplatin\u2010induced cell death through inhibition of DERL1 in mesenchymal\u2010like CD44<sup>high<\/sup> OSCC 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