RT Journal Article
T1 The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53-Independent Manner in Colon and Breast Cancer Cells
A1 Garcia, María Angel
A1 Carrasco, Esther
A1 Aguilera, Margarita
A1 Alvarez, Pablo
A1 Rivas, Carmen
A1 Campos, Joaquín Maria
A1 Prados, José Carlos
A1 Calleja, Miguel Angel
A1 Esteban, Mariano
A1 Marchal, Juan Antonio
A1 Aranega, Antonia
K1 Antimetabolitos Antineoplásicos
K1 Neoplasias de la Mama
K1 Línea Celular Tumoral
K1 Neoplasias del Colon
K1 Femenino
K1 Fluorouracil
K1 Humanos
K1 Fosforilación
K1 eIF-2 Quinasa
AB 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.
PB Public Library of Science
YR 2011
FD 2011-08-24
LK http://hdl.handle.net/10668/406
UL http://hdl.handle.net/10668/406
LA en
NO García  MA, Carrasco E,  Aguilera M,  Alvarez P,  Rivas C, Campos ,JM et al. The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in ap53-independent manner in colon and breast cancer cells. PLoS One. 2011;6(8):e23887
DS RISalud
RD Sep 1, 2025