%0 Journal Article
%A Garcia, María Angel
%A Carrasco, Esther
%A Aguilera, Margarita
%A Alvarez, Pablo
%A Rivas, Carmen
%A Campos, Joaquín Maria
%A Prados, José Carlos
%A Calleja, Miguel Angel
%A Esteban, Mariano
%A Marchal, Juan Antonio
%A Aranega, Antonia
%T The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53-Independent Manner in Colon and Breast Cancer Cells
%D 2011
%U http://hdl.handle.net/10668/406
%X The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR)as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNalpha   treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner,inducing phosphorylation of the protein synthesis translation initiation factor eIF-2alpha and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNalpha combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug.
%K Antimetabolitos Antineoplásicos
%K Neoplasias de la Mama
%K Línea Celular Tumoral
%K Neoplasias del Colon
%K Femenino
%K Fluorouracil
%K Humanos
%K Fosforilación
%K eIF-2 Quinasa
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