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dc.contributor.author | Hugo Villar, Victor | |
dc.contributor.author | Vögler, Oliver | |
dc.contributor.author | Barcelo, Francisca | |
dc.contributor.author | Martin-Broto, Javier | |
dc.contributor.author | Martinez-Serra, Jordi | |
dc.contributor.author | Ruiz-Gutierrez, Valentina | |
dc.contributor.author | Alemany, Regina | |
dc.date.accessioned | 2024-07-09T09:13:16Z | |
dc.date.available | 2024-07-09T09:13:16Z | |
dc.date.issued | 2016-05-24 | |
dc.identifier.citation | Hugo Villar V, Vögler Bernhard O, Barcelo F, Martin-Broto J, Martinez Serra JJ, Ruiz-Gutierrez V, et al. Down-Regulation of AKT Signalling by Ursolic Acid Induces Intrinsic Apoptosis and Sensitization to Doxorubicin in Soft Tissue Sarcoma. PLoS One. 2016 May 24;11(5):e0155946. | en |
dc.identifier.issn | 1932-6203 | |
dc.identifier.other | http://hdl.handle.net/20.500.13003/10359 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20265 | |
dc.description.abstract | Several important biological activities have been attributed to the pentacyclic triterpene ursolic acid (UA), being its antitumoral effect extensively studied in human adenocarcinomas. In this work, we focused on the efficacy and molecular mechanisms involved in the antitumoral effects of UA, as single agent or combined with doxorubicin (DXR), in human soft tissue sarcoma cells. UA (5-50 mu M) strongly inhibited (up to 80%) the viability of STS cells at 24 h and its proliferation in soft agar, with higher concentrations increasing apoptotic death up to 30%. UA treatment (6-9 h) strongly blocked the survival AKT/GSK3 beta/beta-catenin signalling pathway, which led to a concomitant reduction of the anti-apoptotic proteins c-Myc and p21, altogether resulting in the activation of intrinsic apoptosis. Interestingly, UA at low concentrations (10-15 mu M) enhanced the antitumoral effects of DXR by up to 2-fold, while in parallel inhibiting DXR-induced AKT activation and p21 expression, two proteins implicated in antitumoral drug resistance and cell survival. In conclusion, UA is able to induce intrinsic apoptosis in human STS cells and also to sensitize these cells to DXR by blocking the AKT signalling pathway. Therefore, UA may have beneficial effects, if used as nutraceutical adjuvant during standard chemotherapy treatment of STS. | en |
dc.description.sponsorship | Research was supported by the Institute of Health Carlos III through the subprogramme CIBERobn (Centro de Investigacion Biomedica en Red de la Fisiopatologia de la Obesidad y Nutricion). VHV was supported by a predoctoral fellowship from 'Govern de les Illes Balears, Conselleria d'Educacio, Cultura i Universitats' under a program of joint financing with the European Social Fund. | es_ES |
dc.language.iso | eng | en |
dc.publisher | Public Library of Science (PLOS) | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Doxorubicin | * |
dc.subject.mesh | Drug Synergism | * |
dc.subject.mesh | Humans | * |
dc.subject.mesh | Sarcoma | * |
dc.subject.mesh | Antineoplastic Combined Chemotherapy Protocols | * |
dc.subject.mesh | Cell Line, Tumor | * |
dc.subject.mesh | Cell Proliferation | * |
dc.subject.mesh | Cell Survival | * |
dc.subject.mesh | Down-Regulation | * |
dc.subject.mesh | Triterpenes | * |
dc.subject.mesh | Apoptosis | * |
dc.subject.mesh | Proto-Oncogene Proteins c-akt | * |
dc.subject.mesh | Signal Transduction | * |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | * |
dc.title | Down-Regulation of AKT Signalling by Ursolic Acid Induces Intrinsic Apoptosis and Sensitization to Doxorubicin in Soft Tissue Sarcoma | en |
dc.type | research article | en |
dc.rights.license | Attribution 4.0 International | * |
dc.identifier.pubmedID | 27219337 | es_ES |
dc.format.volume | 11 | es_ES |
dc.format.number | 5 | es_ES |
dc.format.page | e0155946 | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0155946 | |
dc.relation.publisherversion | https://dx.doi.org/10.1371/journal.pone.0155946 | en |
dc.identifier.journal | PloS One | es_ES |
dc.rights.accessRights | open access | en |
dc.subject.decs | Transducción de Señal | * |
dc.subject.decs | Línea Celular Tumoral | * |
dc.subject.decs | Regulación Neoplásica de la Expresión Génica | * |
dc.subject.decs | Proliferación Celular | * |
dc.subject.decs | Regulación hacia Abajo | * |
dc.subject.decs | Triterpenos | * |
dc.subject.decs | Apoptosis | * |
dc.subject.decs | Supervivencia Celular | * |
dc.subject.decs | Sarcoma | * |
dc.subject.decs | Humanos | * |
dc.subject.decs | Sinergismo Farmacológico | * |
dc.subject.decs | Protocolos de Quimioterapia Combinada Antineoplásica | * |
dc.subject.decs | Doxorrubicina | * |
dc.subject.decs | Proteínas Proto-Oncogénicas c-akt | * |
dc.identifier.scopus | 2-s2.0-84971572080 | |
dc.identifier.wos | 376880700030 | |
dc.identifier.pui | L610516018 |
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