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The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells
dc.contributor.author | García Chaves, María Ángel | |
dc.contributor.author | Carrasco Pardo, Esther | |
dc.contributor.author | Aguilera Gómez, Margarita | |
dc.contributor.author | Álvarez, Pablo | |
dc.contributor.author | Rivas, Carmen | |
dc.contributor.author | Campos Rosa, Joaquín María | |
dc.contributor.author | Prados Salazar, José Carlos | |
dc.contributor.author | Calleja Hernández, Miguel Ángel | |
dc.contributor.author | Esteban Rodríguez, Mariano | |
dc.contributor.author | Marchal Corrales, Juan Antonio | |
dc.contributor.author | Aránega Jiménez, Antonia | |
dc.date.accessioned | 2014-03-26T13:35:31Z | |
dc.date.available | 2014-03-26T13:35:31Z | |
dc.date.issued | 2011 | |
dc.identifier.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] | es_ES |
dc.identifier.issn | 1932-6203 | |
dc.identifier.other | doi: 10.1371/journal.pone.0023887 | |
dc.identifier.uri | http://hdl.handle.net/10481/31134 | |
dc.description.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. | es_ES |
dc.description.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). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library of Science (PLOS) | es_ES |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | es_ES |
dc.subject | Apoptosis | es_ES |
dc.subject | Breast cancer | es_ES |
dc.subject | Cancer treatment | es_ES |
dc.subject | Colon | es_ES |
dc.subject | Colorectal cancer | es_ES |
dc.subject | Flow cytometry | es_ES |
dc.subject | Phosphorylation | es_ES |
dc.subject | SW480 cells | es_ES |
dc.title | The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells | es_ES |
dc.type | journal article | es_ES |
dc.rights.accessRights | open access | es_ES |