{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:11:09Z","timestamp":1768515069946,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["19481"],"award-info":[{"award-number":["19481"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Despite improvements in oral squamous cell carcinoma (<jats:styled-content style=\"fixed-case\">OSCC<\/jats:styled-content>) management, survival rates remain relatively low and novel anti\u2010neoplastic agents are needed. Bromodomain and extra\u2010terminal (<jats:styled-content style=\"fixed-case\">BET<\/jats:styled-content>) inhibitors proved to be promising agents for cancer treatment. We investigated the effects of three <jats:styled-content style=\"fixed-case\">BET<\/jats:styled-content> inhibitors (<jats:styled-content style=\"fixed-case\">JQ<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">IBET<\/jats:styled-content>\u2010151, <jats:styled-content style=\"fixed-case\">IBET<\/jats:styled-content>\u2010762) on <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>\u201025 cell line and primary oral cancer cell culture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cell viability was evaluated by <jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content>. Protein levels of <jats:styled-content style=\"fixed-case\">MCM<\/jats:styled-content>5 and cleaved\u2010<jats:styled-content style=\"fixed-case\">PARP<\/jats:styled-content> were estimated by Western blot. Clonogenic and migratory abilities were determined by colony forming and scratch assays. <jats:styled-content style=\"fixed-case\">BET<\/jats:styled-content> inhibitors effects on <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of E\u2010Cadherin, Vimentin, <jats:styled-content style=\"fixed-case\">SNAI<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">SNAI<\/jats:styled-content>2, <jats:styled-content style=\"fixed-case\">CLU<\/jats:styled-content>, SERPINI1, <jats:styled-content style=\"fixed-case\">MCM<\/jats:styled-content>5, c\u2010Myc, E2F, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>7R, and <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>g were analyzed by <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">BET<\/jats:styled-content> inhibitors significantly reduced oral cancer cell viability. <jats:styled-content style=\"fixed-case\">JQ<\/jats:styled-content>1 showed the greatest effect reducing cell viability to 10%, both in <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>\u201025 and primary <jats:styled-content style=\"fixed-case\">OSCC<\/jats:styled-content> cultures (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), compared to control cells. Cells treated with <jats:styled-content style=\"fixed-case\">BET<\/jats:styled-content> inhibitors displayed a reduction to 50% in colony forming capacity compared to control cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and the colonies were smaller; they also had a 50%\u201060% reduction in migratory capacity (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) compared to untreated cells. <jats:styled-content style=\"fixed-case\">BET<\/jats:styled-content> inhibitors had a significant impact on genes related to epithelial to mesenchymal transition and other cancer cell markers, notably on <jats:styled-content style=\"fixed-case\">MCM<\/jats:styled-content>5, a gene related to cell cycle control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">BET<\/jats:styled-content> inhibitors induce both <jats:styled-content style=\"fixed-case\">OSCC<\/jats:styled-content> cell death and reduction of tumor aggressiveness. Molecular mechanisms of <jats:styled-content style=\"fixed-case\">BET<\/jats:styled-content> inhibition involve among others, <jats:italic><jats:styled-content style=\"fixed-case\">MCM<\/jats:styled-content>5<\/jats:italic> downregulation. Importantly, this study demonstrates for the first time the anti\u2010tumoral effect of <jats:styled-content style=\"fixed-case\">IBET<\/jats:styled-content>\u2010151 and <jats:styled-content style=\"fixed-case\">IBET<\/jats:styled-content>\u2010762 in oral cancer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12824","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T04:19:14Z","timestamp":1547007554000},"page":"214-221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Biological and molecular effects of bromodomain and extra\u2010terminal (<scp>BET<\/scp>) inhibitors <scp>JQ<\/scp>1, <scp>IBET<\/scp>\u2010151, and <scp>IBET<\/scp>\u2010762 in <scp>OSCC<\/scp> cells"],"prefix":"10.1111","volume":"48","author":[{"given":"Federica","family":"Baldan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties University of Roma \u2018Sapienza'  Roma Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Allegri","sequence":"additional","affiliation":[{"name":"Department of Medical Area University of Udine  Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milos","family":"Lazarevic","sequence":"additional","affiliation":[{"name":"Department of Human Genetics School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catia","family":"Mio","sequence":"additional","affiliation":[{"name":"Department of Medical Area University of Udine  Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Milosevic","sequence":"additional","affiliation":[{"name":"Department of Human Genetics School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Damante","sequence":"additional","affiliation":[{"name":"Department of Medical Area University of Udine  Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-7210","authenticated-orcid":false,"given":"Jelena","family":"Milasin","sequence":"additional","affiliation":[{"name":"Department of Human Genetics School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cden.2017.08.002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcms.2014.04.022"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12733"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.18043"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2018-000743"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2018.03.006"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2013.09.007"},{"key":"e_1_2_7_9_1","first-page":"409","article-title":"MiR\u2010137 silencing of BRD4 suppresses oral squamous cell carcinoma cells proliferation, migration and invasion","volume":"10","author":"He T","year":"2017","journal-title":"Int. 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