Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/89451
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Título

Pharmacological inhibition or small interfering RNA targeting acid ceramidase sensitizes hepatoma cells to chemotherapy and reduces tumor growth in vivo

AutorMorales, Albert CSIC ORCID; París, Raquel; Villanueva, Alberto; Llacuna Duran, Laura CSIC; García-Ruiz, Carmen CSIC ORCID ; Fernández-Checa, José C. CSIC ORCID
Palabras claveCeramide
Apoptosis
Sphingosine-1-phosphate
Mitochondria
Cancer therapy
Fecha de publicación2007
EditorNature Publishing Group
CitaciónOncogene 26(6): 905-916 (2007)
ResumenCeramidases (CDases) play a key role in cancer therapy through enhanced conversion of ceramide into sphingosine 1-phosphate (S1P), but their involvement in hepatocarcinogenesis is unknown. Here, we report that daunorubicin (DNR) activated acid CDase post-transcriptionally in established human (HepG2 cells) or mouse (Hepa1c1c7) hepatoma cell lines as well as in primary cells from murine liver tumors, but not in cultured mouse hepatocytes. Acid CDase silencing by small interfering RNA (siRNA) or pharmacological inhibition with N-oleoylethanolamine (NOE) enhanced the ceramide to S1P balance compared to DNR alone, sensitizing hepatoma cells (HepG2, Hep-3B, SK-Hep and Hepa1c1c7) to DNR-induced cell death. DNR plus NOE or acid CDase siRNA-induced cell death was preceded by ultrastructural changes in mitochondria, stimulation of reactive oxygen species generation, release of Smac/DIABLO and cytochrome c and caspase-3 activation. In addition, in vivo siRNA treatment targeting acid CDase reduced tumor growth in liver tumor xenografts of HepG2 cells and enhanced DNR therapy. Thus, acid CDase promotes hepatocarcinogenesis and its antagonism may be a promising strategy in the treatment of liver cancer. © 2007 Nature Publishing Group All rights reserved.
URIhttp://hdl.handle.net/10261/89451
DOI10.1038/sj.onc.1209834
Identificadoresdoi: 10.1038/sj.onc.1209834
issn: 0950-9232
e-issn: 1476-5594
Aparece en las colecciones: (IIBB) Artículos




Ficheros en este ítem:
Fichero Descripción Tamaño Formato
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo

CORE Recommender

SCOPUSTM   
Citations

89
checked on 15-mar-2024

WEB OF SCIENCETM
Citations

86
checked on 28-feb-2024

Page view(s)

335
checked on 19-mar-2024

Download(s)

94
checked on 19-mar-2024

Google ScholarTM

Check

Altmetric

Altmetric


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