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dc.creatorBaldan, Federica
dc.creatorAllegri, Lorenzo
dc.creatorLazarević, Miloš
dc.creatorCatia, Mio
dc.creatorMilošević, Maja
dc.creatorDamante, Giuseppe
dc.creatorMilašin, Jelena
dc.date.accessioned2020-07-02T13:26:18Z
dc.date.available2020-07-02T13:26:18Z
dc.date.issued2019
dc.identifier.issn0904-2512
dc.identifier.urihttps://smile.stomf.bg.ac.rs/handle/123456789/2457
dc.description.abstractBackground Despite improvements in oral squamous cell carcinoma (OSCC) management, survival rates remain relatively low and novel anti-neoplastic agents are needed. Bromodomain and extra-terminal (BET) inhibitors proved to be promising agents for cancer treatment. We investigated the effects of three BET inhibitors (JQ1, IBET-151, IBET-762) on SCC-25 cell line and primary oral cancer cell culture. Methods Cell viability was evaluated by MTT. Protein levels of MCM5 and cleaved-PARP were estimated by Western blot. Clonogenic and migratory abilities were determined by colony forming and scratch assays. BET inhibitors effects on mRNA levels of E-Cadherin, Vimentin, SNAI1, SNAI2, CLU, SERPINI1, MCM5, c-Myc, E2F, IL7R, and PPARg were analyzed by qPCR. Results BET inhibitors significantly reduced oral cancer cell viability. JQ1 showed the greatest effect reducing cell viability to 10%, both in SCC-25 and primary OSCC cultures (P lt 0.001), compared to control cells. Cells treated with BET inhibitors displayed a reduction to 50% in colony forming capacity compared to control cells (P lt 0.0001) and the colonies were smaller; they also had a 50%-60% reduction in migratory capacity (P lt 0.05) compared to untreated cells. BET inhibitors had a significant impact on genes related to epithelial to mesenchymal transition and other cancer cell markers, notably on MCM5, a gene related to cell cycle control. Conclusions BET inhibitors induce both OSCC cell death and reduction of tumor aggressiveness. Molecular mechanisms of BET inhibition involve among others, MCM5 downregulation. Importantly, this study demonstrates for the first time the anti-tumoral effect of IBET-151 and IBET-762 in oral cancer.en
dc.publisherWiley, Hoboken
dc.relationMinistero degli Affari Esteri of Italy [PGR02954]
dc.relationAssociazione Italiana per la Ricerca sul CancroAssociazione Italiana per la Ricerca sul Cancro (AIRC) [19481]
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175075/RS//
dc.rightsrestrictedAccess
dc.sourceJournal of Oral Pathology & Medicine
dc.subjectBET inhibitorsen
dc.subjectMCM5en
dc.subjectoral canceren
dc.subjectOSCCen
dc.subjectSCC-25en
dc.titleBiological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cellsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractДаманте, Гиусеппе; Aллегри, Лорензо; Цатиа, Мио; Балдан, Федерица; Милашин, Јелена; Лазаревић, Милош; Милошевић, Маја;
dc.citation.volume48
dc.citation.issue3
dc.citation.spage214
dc.citation.epage221
dc.citation.other48(3): 214-221
dc.citation.rankM21
dc.identifier.wos000460347600005
dc.identifier.doi10.1111/jop.12824
dc.identifier.pmid30618144
dc.identifier.scopus2-s2.0-85060654363
dc.type.versionpublishedVersion


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