Proapoptotic and proautophagy effect of H1-receptor antagonist desloratadine in human glioblastoma cell lines.

Glioblastomas are aggressive and usually incurable high-grade gliomas without adequate treatment. In this study, we aimed to investigate the potential of desloratadine to induce apoptosis/autophagy as genetically regulated processes that can seal cancer cell fates. All experiments were performed on U251 human glioblastoma cell line and primary human glioblastoma cell culture. Cytotoxic effect of desloratadine was investigated using MTT and CV assays, while oxidative stress, apoptosis, and autophagy were detected by flow cytometry and immunoblot. Desloratadine treatment decreased cell viability of U251 human glioblastoma cell line and primary human glioblastoma cell culture (IC50 value 50 µM) by an increase of intracellular reactive oxygen species and caspase activity. Also, desloratadine decreased the expression of main autophagy repressor mTOR and its upstream activator Akt and increased the expression of AMPK. Desloratadine exerted dual cytotoxic effect inducing both apoptosis- and mTOR/AMPK-dependent cytotoxic autophagy in glioblastoma cells and primary glioblastoma cell culture.