Quercetin Increases the Efficacy of Glioblastoma Treatment Compared to Standard Chemoradiotherapy by the Suppression of PI-3-Kinase-Akt Pathway

Abstract

The goal of the present study was to compare the efficacy of treatment with irradiation (IR), temozolomide, and quercetin, alone, or in combinations, on 2 glioblastoma cell lines, DBTRG-05 and U-251. Cell viability assay, flow cytometry analysis, colony formation assay, and Western blot analysis were used to compare the effects of treatment on the 2 cell lines. The greatest reduction in cell viability and colony formation was observed when cells were treated with a combination of the agents including quercetin. The treatment of cells with the combination of IR and quercetin was equal to the efficiency of the combination of IR and temozolomide in decreasing cell viability as well as colony formation. Quercetin alone, or in combination with IR, increased the cleavage of caspase-3 and PARP-1 showing an activated apoptosis and significantly reduced the level of phospho-Akt. Moreover, these treatments increased the levels of phospho-ERK, phospho-JNK, phospho-p38, and phospho-RAF1. Our data indicate that the supplementation of standard therapy with quercetin increases efficacy of treatment of experimental glioblastoma through synergism in the induction of apoptosis via the cleavage of caspase-3 and PARP-1 and by the suppression of the actitivation of Akt pathway.

ACKNOWLEDGMENTS

This work was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences and Research Grants from AOK-KA-10-04-2011, AOKKA-34039-1004/2010, AOKKA-34039/KA-OTKA/11-04, AOK-KA 34039/10-24, 34039/KA-OTKA/2011/11-17, OTKA-K-73738, SROP-4.2.2/B-10/1-2010-0029 (Supporting Scientific Training of Talented Youth at the University of Pécs) and SROP-4.2.1.B-10/2/KONV-2010-0002, Developing the South-Transdanubian Regional University Competitiveness. Eva Pozsgai and Szabolcs Bellyei contributed equally to this work.