Abrogation of the p38 MAPK α signaling pathway does not promote radioresistance but its activity is required for 5-Fluorouracil-associated radiosensitivity

• Published in: Cancer letters Vol. 335; no. 1; pp. 66 - 74
• Main Authors: de la Cruz-Morcillo, Miguel A, García-Cano, Jesús, Arias-González, Laura, García-Gil, Elena, Artacho-Cordón, Francisco, Ríos-Arrabal, Sandra, Valero, María L, Cimas, Francisco J, Serrano-Oviedo, Leticia, Villas, María V, Romero-Fernández, Jesús, Núñez, María I, Sánchez-Prieto, Ricardo
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 10.07.2013
• Subjects: 5-Fluorouracil; Antimetabolites, Antineoplastic - pharmacology; Cell Survival - drug effects; Cell Survival - radiation effects; DNA damage; Fluorouracil - pharmacology; Gene Expression; HCT116 Cells; Hematology, Oncology and Palliative Medicine; HT29 Cells; Humans; ionizing radiation; lung neoplasms; MAP Kinase Signaling System; mitogen-activated protein kinase; Mitogen-Activated Protein Kinase 14 - genetics; Mitogen-Activated Protein Kinase 14 - metabolism; p38 MAPK; radiation resistance; Radiation Tolerance - drug effects; Radioresistance; SB203580; signal transduction; viability; Radioresistance; 5-Fluorouracil; SB203580; p38 MAPK
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2013.01.050

The p38 Mitogen Activated Protein Kinase (MAPK) signaling pathway has become a major player in the response to DNA-damage. A growing body of evidences has been relating this signaling pathway to the cellular response to ionizing radiation (IR), suggesting a role in radioresistance. Here, we study the implication of this signaling pathway in the response to IR in terms of radioresistance. To this end we used 10 different cell lines derived from several types of tumors (colorectal, non-small cell lung cancer -NSCLC-, renal and glioblastoma). Although p38 MAPK is transiently activated by IR, our data, obtained by genetic and chemical approaches, showed that this signaling pathway is not implicated in cellular viability after IR exposure. Indeed, down-modulation of this signaling pathway promotes a mild radiosensitivity depending on the cell line. However, it is remarkable that lack of p38 MAPK α abrogates the radiosensitizing effect of 5-Fluorouracil (5-FU) in HCT116 cell line, supporting the role of this MAPK in the radiosensitizing action of 5-FU.