Glioblastoma cell-derived exosomes induce cell death and oxidative stress in primary cultures of olfactory neurons. Role of redox stress

Abstract

BackgroundGlioblastoma multiforme, described as glioblastoma, is a malignancy originating from glial progenitors in the central nervous system and is the most malignant subtype of brain tumors which attracted researcher's attention due to their high recurrence and mortality despite optimal treatments. In the study, we aimed to research whether glioblastoma-originated exosomes play a role in olfactory nerve cell toxicity.Methods and resultsFor this aim, exosomes obtained from U373 and T98G cells were applied to olfactory nerve cell culture at distinct doses. Then, glutathione (GSH), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT), total oxidant status (TOS) and Immunofluorescence analyzes were performed. We found that both glioblastoma-derived exosomes decreased cell viability in olfactory neurons with increasing doses. According to the obtained data, the olfactory neuron vitality rate was 71% in T98G-exosome, but the decrease in U373-exosome was more obvious (48%). In particular, the 100 mu g/ml dose exacerbated oxidative stress by increasing TOS. It also increased cellular apoptosis compared to the control group due to LDH leakage. However, the results of GSH and TAS showed that antioxidant levels were significantly reduced.ConclusionIn the microenvironment of olfactory neurons, GBM-derived exosomes increased oxidative stress-induced toxicity by reducing TAC and GSH levels. Therefore, glioblastoma cells by induction of exosome-based stress support malignant growth.