List of communications


Control of the redox balance in glioblastoma multiforme: impact on tumor metabolism, neovascularization and inflammation

Javier Frontiñán-Rubio 1, Faculty of Medicine, University of Castilla-La Mancha, Ciudad Real, Spain; Raquel Santiago-Mora 1, Faculty of Medicine, University of Castilla-La Mancha, Ciudad Real, Spain; Alicia Martínez-González 2, IMACI, University of Castilla-La Mancha, Ciudad Real, Spain; María Victoria Gómez-Almagro 3; IRICA, University of Castilla-La Mancha, Ciudad Real, Spain; Margarita Villar-Rayo 4; IREC, CSIC-University of Castilla-La Mancha, Ciudad Real, Spain; Gustavo Ferrín-Sánchez 5; IMIBIC-CIBEREHD, Córdoba, Spain; Gabriel Fernández-Calvo 2; IMACI, University of Castilla-La Mancha, Ciudad Real, Spain; Luis Pérez-Romasanta 6; Radiation Oncology Unit, Universitary Hospital of Salamanca, Spain; Juan Ramón Peinado 1; Faculty of Medicine, University of Castilla-La Mancha, Ciudad Real, Spain; Victor Manuel Pérez-García 2; IMACI, University of Castilla-La Mancha, Ciudad Real, Spain; Francisco Javier Alcaín 1; Faculty of Medicine, University of Castilla-La Mancha, Ciudad Real, Spain; Mario Durán-Prado 1; Faculty of Medicine, University of Castilla-La Mancha, Ciudad Real, Spain.


Elevated mitochondrial superoxide radical (O2.-) is linked to the aggressive features of GBM. O2.- dismutates to H2O2, translocates to the cytosol and triggers pathways that favor tumor progression. Increased O2.- and H2O2 levels stabilize HIF1-α, even in normoxia, which promotes the “glycolitic swicht” and initiates neovascularization, which, added to the attraction of inflammatory cells, facilitates tumor growth and invasion. Herein, we show how coenzyme Q10 (CoQ), a lipophilic antioxidant and a component of the mitochondrial electron transport chain, can normalize the level of O2.-, H2O2, HIF1-α and several other key signaling molecules governing GBM progression. To that purpose, using molecular and cell biology approaches as well as “omics”, we have tested the effect of CoQ using human GBM cell lines in vitro, and in vivo, xenografted subcutaneously or ortotopically implantated into the striatum of nu/nu mice. Treatment with CoQ reduced O2.- and H2O2 levels in 50%, accompanied by an increase in complex II-associated respiration. These results are paralleled by a decrease in cell viability and motility, as consequence of the modification of the full proteome and to a decrease in the aerobic glycolisys rate. These results were reproduced in vivo. In subcutaneous xenografts of GBM, CoQ reduced tumor volume by a direct action on tumor cells but also by regulating neovascularization and local inflammation. Indeed, similar results were obtained in ortotophic models, where CoQ not only reduced the volume of primary tumors, also, and dramatically, impeded tumor cells infiltration. As a whole, our results presented herein appoint towards CoQ as a pleiotropic regulator of GBM progression and pave the way for the implementation of further therapeutic modalities to manage this devasting pathology.

Format: Oral communication

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