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Autophagy involvement in olanzapine-mediated cytotoxic effects in human glioma cells.
- Source :
-
Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2014; Vol. 15 (19), pp. 8107-13. - Publication Year :
- 2014
-
Abstract
- The aim of this study was to investigate the effects of olanzapine on growth inhibition as well as autophagy in glioma cells in vitro and in vivo. The proliferation of both LN229 and T98 glioma cells, measured by MTT assay, was suppressed in a concentration-dependent and time-dependent manner. Moreover, apoptosis of both cells was significantly increased with the treatment of olanzapine as evidenced by increased Bcl-2 expression, Hoechst 33258 staining and annexinV-FITC/PI staining. Olanzapine treatment also enhanced activation of autophagy with increased expression of LC3-II, expression of protein p62, a substrate of autophagy, being decreased. The growth inhibition by olanzapine in both glioma cell lines could be blocked by co-treatment with 3-MA, an autophagy inhibitor. Furthermore, olanzapine effectively blocked the growth of subcutaneous xenografts of LN229 glioma cells in vivo. The increased level of protein LC3-II and decreased level of p62 followed by a decreased level of Bcl-2, suggesting that autophagy may contribute to apoptosis. In addition, reduced proliferation of glioma cells was shown by a decrease of Ki-67 staining and increased caspase-3 staining indicative of apoptosis in mouse xenografts. These results indicated that olanzapine inhibited the growth of glioma cells accompanied by induction of autophagy and apoptosis both in vitro and in vivo. Olanzapine-induced autophagy plays a tumor-suppressing role in glioma cells.
- Subjects :
- Animals
Biomarkers, Tumor metabolism
Blotting, Western
Brain Neoplasms metabolism
Brain Neoplasms pathology
Brain Neoplasms prevention & control
Cell Proliferation drug effects
Flow Cytometry
Glioma metabolism
Glioma prevention & control
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Olanzapine
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Apoptosis drug effects
Autophagy drug effects
Benzodiazepines pharmacology
Glioma pathology
Selective Serotonin Reuptake Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2476-762X
- Volume :
- 15
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Asian Pacific journal of cancer prevention : APJCP
- Publication Type :
- Academic Journal
- Accession number :
- 25338992
- Full Text :
- https://doi.org/10.7314/apjcp.2014.15.19.8107