Coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide by inhibiting catalase activity, lactate and glutathione synthesis
2017 - J Frontiñán, R Santiago-Mora, A MartínezGonzález, MV Gómez-Almagro, J Ariza, E Lozano, J Arjona, A Gil, M Pesic, J Peinado, J Villalba, L PérezRomasanta, VM Pérez-García, FJ Alcain, M Duran-Prado
BMC Cancer (2017, submitted)
Resumen
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults. GBM is highly radioresistant due to several reasons including the basal overproduction of mitochondrial radical oxygen species, ROS, and the increase of diverse antioxidant systems. Increased ROS induce a feedback on glycolysis and lactate production, increases catalase and the level of glutathione. Glutathione is involved in resistance to temozolomide, the current standard chemotherapeutical in GBM treatment. Here we describe several effects of the lipophilic antioxidant coenzyme Q10 (CoQ), on radiation-induced apoptosis in human GBM U251 cells. CoQ targets ROS produced in the mitochondria. Our results demonstrate that CoQ decreases O2.- and H2O2, the levels of intracellular lactate and cell viability. It also decreases catalase activity as well as the level of glutathione, both involved in radioresistance. CoQ-treated cells were more sensitive to radiation-induced apoptosis in short and long-term clonogenic assays, synergizing with temozolomide. The results show a strong radiosensitizing effect of CoQ that could prove useful in clinical practice.