{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:48:26Z","timestamp":1790023706430,"version":"4.0.1"},"reference-count":55,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Institutes of T\u00fcrkiye","award":["12082"],"award-info":[{"award-number":["12082"]}]},{"award":["12082"],"award-info":[{"award-number":["12082"]}],"id":[{"id":"https:\/\/ror.org\/01d6ka036","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colon cancer remains a leading cause of cancer-related deaths, and drug repurposing offers a promising strategy to identify new therapies. Hydroquinidine (HQ), a class I antiarrhythmic agent, has recently been suggested to possess anticancer properties; however, its preclinical safety and efficacy in colorectal cancer are not well defined. The safety of HQ was evaluated in Wistar rats following OECD guidelines. Rats received daily intraperitoneal doses (2.5\u201325 mg\/kg) for 90 days, with hematological, biochemical, and histopathological assessments performed. HQ was well tolerated up to 12.5 mg\/kg, whereas 25 mg\/kg caused signs of hepatotoxicity without lethality. A 1,2-dimethylhydrazine-induced colorectal cancer model was then used to assess HQ at safe doses (6.25 and 12.5 mg\/kg) compared with cisplatin. Tissue histopathology and selected molecular markers associated with inflammation, apoptosis, epithelial\u2013mesenchymal transition, and PI3K\/AKT\/mTOR pathway activity were analyzed. In the DMH-induced colon cancer model, HQ improved colonic tissue architecture and was associated with lower histopathological scores compared with untreated tumor controls. HQ also modulated tumor-associated markers by reducing IL-6 immunoreactivity, increasing caspase-3 expression, enhancing E-cadherin immunoreactivity, and decreasing vimentin expression. Moreover, HQ was associated with reduced immunoreactivity of mTOR pathway-related markers, suggesting attenuation of pathway activation in this experimental context. Overall, HQ showed an acceptable safety profile at the selected doses and exerted favorable histopathological and molecular modulatory effects, supporting further investigation as a potential repurposing candidate.<\/jats:p>","DOI":"10.3390\/ijms27135672","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hydroquinidine Modulates Histopathological, Inflammatory, Apoptotic, EMT-Related, and PI3K\/AKT\/mTOR-Associated Markers in a DMH-Induced Rat Model of Colon Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"\u0130lknur","family":"Keskin","sequence":"first","affiliation":[{"name":"Histology and Embryology Department, School of Medicine, \u0130stanbul Medipol University, \u0130stanbul 34810, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beg\u00fcm","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Program of Histology and Embryology, Institute of Health Sciences, \u0130stanbul Medipol University, \u0130stanbul 34810, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"B\u00fclb\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Milas Veterinary Medicine, Mu\u011fla S\u0131tk\u0131 Kocman University, Mu\u011fla 48200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"\u00c7ak\u0131r","sequence":"additional","affiliation":[{"name":"Veterinary Physiology Program, Institute of Health Sciences, Mu\u011fla S\u0131tk\u0131 Kocman University, Mu\u011fla 48200, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervenur","family":"Yavuz","sequence":"additional","affiliation":[{"name":"Molecular Biology and Genetics Program, Institute of Natural Sciences, Mu\u011fla S\u0131tk\u0131 Kocman University, Mu\u011fla 48000, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1526-2065","authenticated-orcid":false,"given":"Muhammet Volkan","family":"B\u00fclb\u00fcl","sequence":"additional","affiliation":[{"name":"Histology and Embryology Department, School of Medicine, A\u011fr\u0131 \u0130brahim \u00c7e\u00e7en University, A\u011fr\u0131 04000, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Turan","family":"Demircan","sequence":"additional","affiliation":[{"name":"Medical Biology Department, School of Medicine, \u0130zmir Bakircay University, \u0130zmir 35665, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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