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dc.contributor.authorEritja Sánchez, Núria
dc.contributor.authorBergadà Bertran, Laura
dc.contributor.authorSorolla Bardají, Anabel
dc.contributor.authorYeramian Hakim, Andree
dc.contributor.authorMirantes, Cristina
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorDolcet Roca, Xavier
dc.date.accessioned2018-09-27T15:09:03Z
dc.date.available2018-09-27T15:09:03Z
dc.date.issued2013
dc.identifier.issn1574-7891
dc.identifier.urihttp://hdl.handle.net/10459.1/64790
dc.description.abstractHistone 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.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.molonc.2013.03.003ca_ES
dc.relation.ispartofMolecular oncology, 2013, núm. 7, p. 763-775ca_ES
dc.rights(c) Elsevier, 2013ca_ES
dc.rights(c) Federation of European Biochemical Societiesca_ES
dc.subjectVorinostatca_ES
dc.subjectCàncer endometrialca_ES
dc.subjectCaspase-8ca_ES
dc.titleCombination of Vorinostat and caspase-8 inhibition exhibitshigh anti-tumoral activity on endometrial cancer cellsca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.identifier.idgrec019390
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.1016/j.molonc.2013.03.003


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