Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells
Samo za registrovane korisnike
2019
Autori
Baldan, FedericaAllegri, Lorenzo
Lazarević, Miloš
Catia, Mio
Milošević, Maja
Damante, Giuseppe
Milašin, Jelena
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Background 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 i...nhibitors 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.
Ključne reči:
BET inhibitors / MCM5 / oral cancer / OSCC / SCC-25Izvor:
Journal of Oral Pathology & Medicine, 2019, 48, 3, 214-221Izdavač:
- Wiley, Hoboken
Finansiranje / projekti:
- Ministero degli Affari Esteri of Italy [PGR02954]
- Associazione Italiana per la Ricerca sul CancroAssociazione Italiana per la Ricerca sul Cancro (AIRC) [19481]
- Genetička kontrola i molekularni mehanizmi u malignim, inflamatornim i razvojnim patologijama orofacijalne regije (RS-MESTD-Basic Research (BR or ON)-175075)
DOI: 10.1111/jop.12824
ISSN: 0904-2512
PubMed: 30618144
WoS: 000460347600005
Scopus: 2-s2.0-85060654363
Kolekcije
Institucija/grupa
Stomatološki fakultetTY - JOUR AU - Baldan, Federica AU - Allegri, Lorenzo AU - Lazarević, Miloš AU - Catia, Mio AU - Milošević, Maja AU - Damante, Giuseppe AU - Milašin, Jelena PY - 2019 UR - https://smile.stomf.bg.ac.rs/handle/123456789/2457 AB - Background 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. PB - Wiley, Hoboken T2 - Journal of Oral Pathology & Medicine T1 - Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells VL - 48 IS - 3 SP - 214 EP - 221 DO - 10.1111/jop.12824 ER -
@article{ author = "Baldan, Federica and Allegri, Lorenzo and Lazarević, Miloš and Catia, Mio and Milošević, Maja and Damante, Giuseppe and Milašin, Jelena", year = "2019", abstract = "Background 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.", publisher = "Wiley, Hoboken", journal = "Journal of Oral Pathology & Medicine", title = "Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells", volume = "48", number = "3", pages = "214-221", doi = "10.1111/jop.12824" }
Baldan, F., Allegri, L., Lazarević, M., Catia, M., Milošević, M., Damante, G.,& Milašin, J.. (2019). Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells. in Journal of Oral Pathology & Medicine Wiley, Hoboken., 48(3), 214-221. https://doi.org/10.1111/jop.12824
Baldan F, Allegri L, Lazarević M, Catia M, Milošević M, Damante G, Milašin J. Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells. in Journal of Oral Pathology & Medicine. 2019;48(3):214-221. doi:10.1111/jop.12824 .
Baldan, Federica, Allegri, Lorenzo, Lazarević, Miloš, Catia, Mio, Milošević, Maja, Damante, Giuseppe, Milašin, Jelena, "Biological and molecular effects of bromodomain and extra-terminal (BET) inhibitors JQ1, IBET-151, and IBET-762 in OSCC cells" in Journal of Oral Pathology & Medicine, 48, no. 3 (2019):214-221, https://doi.org/10.1111/jop.12824 . .