English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/145655
Título

Down-Regulation of AKT Signalling by Ursolic Acid Induces Intrinsic Apoptosis and Sensitization to Doxorubicin in Soft Tissue Sarcoma

AutorVillar, V.H.; Vögler, O.; Barceló, F.; Martín-Broto, J.; Martínez-Serra, J.; Ruiz-Gutiérrez, Valentina
Fecha de publicación24-may-2016
EditorPublic Library of Science
CitaciónPLoS ONE 11 (5): e0155946 (2016)
ResumenSeveral 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 μM) 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/GSK3β/β-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 μM) 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.
Descripción15 Páginas; 6 Figuras
Versión del editorhttp://dx.doi.org/10.1371/journal.pone.0155946
URIhttp://hdl.handle.net/10261/145655
DOI10.1371/journal.pone.0155946
E-ISSN1932-6203
Aparece en las colecciones: (IG) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
PlosOne_2016_11_5_e.0155946.pdfArtículo principal2,81 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.