Publication: The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53-Independent Manner in Colon and Breast Cancer Cells
dc.contributor.author | Garcia, María Angel | |
dc.contributor.author | Carrasco, Esther | |
dc.contributor.author | Aguilera, Margarita | |
dc.contributor.author | Alvarez, Pablo | |
dc.contributor.author | Rivas, Carmen | |
dc.contributor.author | Campos, Joaquín Maria | |
dc.contributor.author | Prados, José Carlos | |
dc.contributor.author | Calleja, Miguel Angel | |
dc.contributor.author | Esteban, Mariano | |
dc.contributor.author | Marchal, Juan Antonio | |
dc.contributor.author | Aranega, Antonia | |
dc.contributor.authoraffiliation | [García,MA] Unidad de Investigación, Hospital Universitario Virgen de las Nieves, Granada, Spain.[Aguilera,M] Unidad de Farmacogenética, Hospital Universitario Virgen de las Nieves, Granada, Spain.[García,MA; Carrasco,E; Alvarez,P; Prados,JC; Marchal,JA; Aránega,A] Instituto de Biopatología y Medicina Regenerativa (IBIMER), Universidad de Granada,Granada, Spain. [Rivas,C] Centro Nacional de Biotecnología, CSIC, Madrid,Spain. [Campos,JM] Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Granada, Spain. | es |
dc.contributor.funder | 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). No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript | |
dc.date.accessioned | 2012-06-12T08:02:59Z | |
dc.date.available | 2012-06-12T08:02:59Z | |
dc.date.issued | 2011-08-24 | |
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/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. | es |
dc.description.version | Yes | es |
dc.identifier.citation | 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 | es |
dc.identifier.doi | 10.1371/journal.pone.0023887 | |
dc.identifier.essn | 1932-6203 | |
dc.identifier.pmid | 21887339 | |
dc.identifier.uri | http://hdl.handle.net/10668/406 | |
dc.journal.title | PLoS One | |
dc.language.iso | en | |
dc.publisher | Public Library of Science | es |
dc.relation.publisherversion | http://dx.plos.org/10.1371/journal.pone.0023887 | es |
dc.rights.accessRights | open access | |
dc.subject | Antimetabolitos Antineoplásicos | es |
dc.subject | Neoplasias de la Mama | es |
dc.subject | Línea Celular Tumoral | es |
dc.subject | Neoplasias del Colon | es |
dc.subject | Femenino | es |
dc.subject | Fluorouracil | es |
dc.subject | Humanos | es |
dc.subject | Fosforilación | es |
dc.subject | eIF-2 Quinasa | es |
dc.subject.mesh | Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antimetabolites::Antimetabolites, Antineoplastic | es |
dc.subject.mesh | Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms | es |
dc.subject.mesh | Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor | es |
dc.subject.mesh | Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colonic Neoplasms | es |
dc.subject.mesh | Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil | es |
dc.subject.mesh | Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans | es |
dc.subject.mesh | Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation | es |
dc.subject.mesh | Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::eIF-2 Kinase | es |
dc.title | The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53-Independent Manner in Colon and Breast Cancer Cells | es |
dc.type | research article | |
dc.type.hasVersion | VoR | |
dspace.entity.type | Publication |
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