{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:52:19Z","timestamp":1772160739128,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mucoepidermoid carcinoma (MEC) is the most prevalent salivary gland malignancy, with a poor prognosis in high\u2010grade tumors at diagnosis. This highlights the need for effective antitumor agents for treating MEC. Therefore, we aimed to investigate the antineoplastic efficacy of pyrimethamine (PYR), a Food and Drug Administration\u2010approved antiparasitic medicine, to repurpose it as an alternative therapeutic option for treating human MEC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The trypan blue exclusion assay, cell counting kit\u20108 assay, and live\/dead assay were performed to assess the antiproliferative efficacy of PYR. PYR\u2010induced apoptosis was confirmed with 4\u2032,6\u2010diamidino\u20102\u2010phenylindole staining, cell cycle analysis, and annexin V\/propidium iodide staining. A western blot assay was conducted to measure changes in cleaved caspase 8 and myeloid cell leukemia\u20101 (Mcl\u20101) expression after PYR treatment. Mcl\u20101 overexpression was used to further confirm the apoptosis\u2010inducing activity of PYR. The hanging drop method was employed to assess the efficacy of PYR in a three\u2010dimensional culture system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PYR\u2010induced apoptotic cell death in the YD\u201015 high\u2010grade MEC cell line by promoting apoptosis, as evidenced by MCl\u20101 proteasomal degradation and increased cleaved caspase 8 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results indicate that PYR can effectively target human MEC by inducing both intrinsic and extrinsic apoptotic pathways.<\/jats:p>\n                  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