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Title: The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53-Independent Manner in Colon and Breast Cancer Cells
Authors: Garcia, María Angel
Carrasco, Esther
Aguilera, Margarita
Alvarez, Pablo
Rivas, Carmen
Campos, Joaquín Maria
Prados, José Carlos
Calleja, Miguel Angel
Esteban, Mariano
Marchal, Juan Antonio
Aranega, Antonia
metadata.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.
Keywords: Antimetabolitos Antineoplásicos;Neoplasias de la Mama;Línea Celular Tumoral;Neoplasias del Colon;Femenino;Fluorouracil;Humanos;Fosforilación;eIF-2 Quinasa
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antimetabolites::Antimetabolites, Antineoplastic
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colonic Neoplasms
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation
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
Issue Date: 24-Aug-2011
Publisher: Public Library of Science
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
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.
metadata.dc.identifier.doi: 10.1371/journal.pone.0023887
ISSN: 1932-6203 (Online)
Appears in Collections:01- Artículos - Hospital Virgen de las Nieves

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