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

Autor:	Yajie Xiong, Yifan Zhao, Yan Wang, Xiao Shen, Rui‐Si Liu, Ying Zhu, Zhongqin Liang
Rok vydání:	2019
Předmět:	0301 basic medicine Olanzapine autophagy Cell Survival olanzapine Antineoplastic Agents Inhibitory postsynaptic potential 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Annexin Cell Line Tumor Physiology (medical) Glioma medicine Humans Pharmacology (medical) Pharmacology Dose-Response Relationship Drug Chemistry NF‐κB Autophagy NF-kappa B NF-κB Original Articles medicine.disease Blot Psychiatry and Mental health 030104 developmental biology Cancer research Original Article Tumor necrosis factor alpha MGMT Selective Serotonin Reuptake Inhibitors 030217 neurology & neurosurgery medicine.drug
Zdroj:	CNS Neuroscience & Therapeutics
ISSN:	1755-5949 1755-5930
DOI:	10.1111/cns.13127
Popis:	Summary 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f30f8ef1eb37239de1ad0b1fe2bef303 https://doi.org/10.1111/cns.13127 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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