English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/134615
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

Endoplasmic reticulum targeting in Ewing's sarcoma by the alkylphospholipid analog edelfosine

AutorBonilla, Ximena; Dakir, El Habib; Mollinedo, Faustino ; Gajate, Consuelo
Palabras claveEther phospholipid
Edelfosine
Xenograft animal model
Apoptosis
Endoplasmic reticulum
Ewing’s sarcoma
Fecha de publicación2015
EditorImpact Journals
CitaciónOncotarget 6(16): 14596-14613 (2015)
ResumenEwing’s sarcoma (ES) is the second most common bone cancer in children and young people. Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) is the prototype of a family of synthetic antitumor compounds, collectively known as alkylphospholipid analogs (APLs). We have found that APLs ranked edelfosine>perifosine>erucylphosphocholine>miltefosine for their capacity to promote apoptosis in ES cells. Edelfosine accumulated in the endoplasmic reticulum (ER) and triggered an ER stress response that eventually led to caspase-dependent apoptosis in ES cells. This apoptotic response involved mitochondrial-mediated processes, with cytochrome c release, caspase-9 activation and generation of reactive oxygen species. Edelfosine-induced apoptosis was also dependent on sustained c-Jun NH2-terminal kinase activation. Oral administration of edelfosine showed a potent in vivo antitumor activity in an ES xenograft animal model. Histochemical staining gave evidence for ER stress response and apoptosis in the ES tumors isolated from edelfosine-treated mice. Edelfosine showed a preferential action on ES tumor cells as compared to non-transformed osteoblasts, and appeared to be well suited for combination therapy regimens. These results demonstrate in vitro and in vivo antitumor activity of edelfosine against ES cells that is mediated by caspase activation and ER stress, and provide the proof of concept for a putative edelfosine- and ER stress-mediated approach forES treatment.
DescripciónThis is an open-access article distributed under the terms of the Creative Commons Attribution License.
Versión del editorhttp://dx.doi.org/10.18632/oncotarget.4053
URIhttp://hdl.handle.net/10261/134615
DOI10.18632/oncotarget.4053
Identificadoresdoi: 10.18632/oncotarget.4053
e-issn: 1949-2553
Aparece en las colecciones: (IBMCC) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
alkylphospholipid.pdf6,86 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.