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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/31134

Title: The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells
Authors: García Cháves, María Ángeles
Carrasco Pardo, Esther
Aguilera Gómez, Margarita
Álvarez, Pablo
Rivas, Carmen
Campos Rosa, Joaquín M.
Prados Salazar, José Carlos
Calleja Hernández, Miguel Ángel
Esteban Rodríguez, Mariano
Marchal Corrales, Juan Antonio
Aránega Jiménez, Antonia
Issue Date: 2011
Abstract: 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/IFNα 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-2α 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/IFNα 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.
Sponsorship: This work was supported in part by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria projects n°. CP08/0063, PI07/0527 and PI10/02295).
Publisher: Public Library of Science (PLOS)
Keywords: Apoptosis
Breast cancer
Cancer treatment
Colon
Colorectal cancer
Flow cytometry
Phosphorylation
SW480 cells
URI: http://hdl.handle.net/10481/31134
ISSN: 1932-6203
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: García, M.A.; et al. The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells. Plos One, 6(8): e23887 (2011). [http://hdl.handle.net/10481/31134]
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