dc.contributor |
Universitat de Barcelona |
dc.contributor.author |
Peña Rico, Miguel A. |
dc.contributor.author |
Calvo-Vidal, María Nieves |
dc.contributor.author |
Vilallonga Planells, Ruth |
dc.contributor.author |
Martínez Soler, Fina |
dc.contributor.author |
Giménez Bonafé, Pepita |
dc.contributor.author |
Navarro i Sabaté, Àurea |
dc.contributor.author |
Tortosa i Moreno, Avelina |
dc.contributor.author |
Bartrons Bach, Ramon |
dc.contributor.author |
Manzano Cuesta, Anna |
dc.date |
2012-12-05T10:25:19Z |
dc.date |
2012-12-05T10:25:19Z |
dc.date |
2011-11 |
dc.date |
2012-12-05T10:25:19Z |
dc.identifier.citation |
0167-8140 |
dc.identifier.citation |
600411 |
dc.identifier.uri |
http://hdl.handle.net/2445/33005 |
dc.format |
8 p. |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
Elsevier B.V. |
dc.relation |
Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.radonc.2011.07.002 |
dc.relation |
Radiotherapy and Oncology, 2011, vol. 101, num. 1, p. 132-139 |
dc.relation |
http://dx.doi.org/10.1016/j.radonc.2011.07.002 |
dc.rights |
(c) Elsevier B.V., 2011 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Glioma |
dc.subject |
Proteïnes supressores de tumors |
dc.subject |
Gliomas |
dc.subject |
Tumor suppressor protei |
dc.title |
TP53 induced glycolysis and apoptosis regulator (TIGAR) knockdown results in radiosensitization of glioma cells |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/acceptedVersion |
dc.description.abstract |
Background and purpose: The TP53 induced glycolysis and apoptosis regulator (TIGAR) functions to lower fructose-2,6-bisphosphate (Fru-2,6-P2) levels in cells, consequently decreasing glycolysis and leading to the scavenging of reactive oxygen species (ROS), which correlate with a higher resistance to cell death. The decrease in intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic lesions. Given these good prospects of TIGAR for metabolic regulation and p53-response modulation, we analyzed the effects of TIGAR knockdown in U87MG and T98G glioblastoma-derived cell lines. Methods/results: After TIGAR-knockdown in glioblastoma cell lines, different metabolic parameters were assayed, showing an increase in Fru-2,6-P2, lactate and ROS levels, with a concomitant decrease in reduced glutathione (GSH) levels. In addition, cell growth was inhibited without evidence of apoptotic or autophagic cell death. In contrast, a clear senescent phenotype was observed. We also found that TIGAR protein levels were increased shortly after irradiation. In addition, avoiding radiotherapy-triggered TIGAR induction by gene silencing resulted in the loss of capacity of glioblastoma cells to form colonies in culture and the delay of DNA repair mechanisms, based in c-H2AX foci, leading cells to undergo morphological changes compatible with a senescent phenotype. Thus, the results obtained raised the possibility to consider TIGAR as a therapeutic target to increase radiotherapy effects. Conclusion: TIGAR abrogation provides a novel adjunctive therapeutic strategy against glial tumors by increasing radiation-induced cell impairment, thus allowing the use of lower radiotherapeutic doses. |