Evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and extract against C6 glioma cells.

Glioblastoma multiforme is a malignant neoplasm of the brain with poor prognosis. The first-line drug against glioblastoma is the alkylating agent temozolamide (TMZ); unfortunately, treatment resistance and tumor re-incidence are common. In some cases, immunogenic cell death (ICD) inducers can decrease treatment resistance and tumor recurrence by stimulating an antitumor specific immune response. Not all ICD inducers, however, are suitable for glioma patients because of the low permeability of the blood-brain barrier (BBB). Panobinostat (PAN), a histone deacetylase inhibitor and extract can pass through the BBB and have antitumor properties. The aim of this study is to evaluate the cytotoxic potential of TMZ, PAN and extract against the glioma C6 cell line, and its role in the release of damage-associated molecular patterns (DAMPs), which is a hallmark of ICD. Our results indicate that all treatments induce cellular death in a time- and concentration-dependent manner, and that PAN and extract induce apoptosis, whereas TMZ induces apoptosis and necrosis. Also, that some of the treatments and their sequential administration induce the release of DAMPs. Furthermore, in a rat glioma model, we observed that all treatments decreased tumor volume, but the cell death mechanism was not ICD. Our findings indicate that TMZ, PAN, and combination have a cytotoxic effect against glioma cells but do not induce ICD.