Combination of Vorinostat and caspase-8 inhibition exhibitshigh anti-tumoral activity on endometrial cancer cells
| dc.contributor.author | Eritja Sánchez, Núria | |
| dc.contributor.author | Bergadà Bertran, Laura | |
| dc.contributor.author | Sorolla Bardají, Anabel | |
| dc.contributor.author | Yeramian Hakim, Andree | |
| dc.contributor.author | Mirantes, Cristina | |
| dc.contributor.author | Matias-Guiu, Xavier | |
| dc.contributor.author | Dolcet Roca, Xavier | |
| dc.date.accessioned | 2018-09-27T15:09:03Z | |
| dc.date.available | 2018-09-27T15:09:03Z | |
| dc.date.issued | 2013 | |
| dc.description.abstract | Histone deacetylase inhibitors such as Vorinostat display anti-neoplastic activity against avariety of solid tumors. Here, we have investigated the anti-tumoral activity of Vorinostaton endometrial cancer cells. We have found that Vorinostat caused cell growth arrest, lossof clonogenic growth and apoptosis of endometrial cancer cells. Vorinostat-induced theactivation of caspase-8 and -9, the initiators caspases of the extrinsic and the intrinsicapoptotic pathways, respectively. Next, we investigated the role of the extrinsic pathwayin apoptosis triggered by Vorinostat. We found that Vorinostat caused a dramatic decreaseof FLIP mRNA and protein levels. However, overexpression of the long from of FLIP did notblock Vorinostat-induced apoptosis. To further investigate the role of extrinsic apoptoticpathway in Vorinostat-induced apoptosis, we performed an shRNA-mediated knock-down of caspase-8. Surprisingly, downregulation of caspase-8 alone caused a markeddecrease in clonogenic ability and reduced the growth of endometrial cancer xenograftsin vivo, revealing that targeting caspase-8 may be an attractive target for anticancer ther-apy on endometrial tumors. Furthermore, combination of caspase-8 inhibition and Vorino-stat treatment caused an enhancement of apoptotic cell death and a further decrease ofclonogenic growth of endometrial cancer cells. More importantly, combination of Vorino-stat and caspase-8 inhibition caused a nearly complete inhibition of tumor xenograftgrowth. Finally, we demonstrate that cell death triggered by Vorinostat alone or incombination with caspase-8 shRNAs was inhibited by the anti-apoptotic protein Bcl-XL.Our results suggest that combinatory therapies using Vorinostat treatment and caspase-8 inhibition can be an effective treatment for endometrial carcinomas. | ca_ES |
| dc.identifier.doi | https://doi.org/10.1016/j.molonc.2013.03.003 | |
| dc.identifier.idgrec | 019390 | |
| dc.identifier.issn | 1574-7891 | |
| dc.identifier.uri | http://hdl.handle.net/10459.1/64790 | |
| dc.language.iso | eng | ca_ES |
| dc.publisher | Elsevier | ca_ES |
| dc.relation.isformatof | Reproducció del document publicat a https://doi.org/10.1016/j.molonc.2013.03.003 | ca_ES |
| dc.relation.ispartof | Molecular oncology, 2013, núm. 7, p. 763-775 | ca_ES |
| dc.rights | (c) Elsevier, 2013 | ca_ES |
| dc.rights | (c) Federation of European Biochemical Societies | ca_ES |
| dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_ES |
| dc.subject | Vorinostat | ca_ES |
| dc.subject | Càncer endometrial | ca_ES |
| dc.subject | Caspase-8 | ca_ES |
| dc.title | Combination of Vorinostat and caspase-8 inhibition exhibitshigh anti-tumoral activity on endometrial cancer cells | ca_ES |
| dc.type | info:eu-repo/semantics/article | ca_ES |
| dc.type.version | info:eu-repo/semantics/publishedVersion | ca_ES |