Olanzapine induced autophagy through suppression of NF-κB activation in human glioma cells

Abstract

Aims: Our laboratory previously reported that olanzapine treatment inhibited growth of glioma cell lines and hypothesized that autophagy may be involved in the proliferation inhibitory effects of olanzapine. However, the mechanisms of olanzapine-contributed autophagy activation are unclear. Methods: The inhibitory effects of olanzapine on glioma cells were evaluated by CCK8 assay, Hoechst 33258 staining and annexin V-FITC/PI staining. Western blotting, nuclear separation techniques, and immunofluorescence assays were used to investigate the relationship between the inhibition of NF-κB and autophagy activation by olanzapine. Results: In this work, we verified that olanzapine increased autophagic flux and autophagic vesicles. In addition, we confirmed that autophagy was related to NF-κB inhibition in cancer progression, especially with the nuclear translocation of p65. Furthermore, we demonstrated that autophagy induced by olanzapine could be impaired with TNFα cotreatment. We also found that olanzapine had an inhibitory effect on T98 cells with positive MGMT protein expression, which may involve the inhibition of MGMT through effects on NF-κB. Conclusions: Our findings identify a pathway by which olanzapine induces autophagy by depressing NF-κB in a glioma cell line, providing evidence which supports the use of olanzapine as a potential anticancer drug.