Tetrandrine inhibits glioma stem-like cells by repressing β-catenin expression
| Autor: | Chao-Yue Meng, Yong Zhang, Xiao-Ze Xu, Jianxian Huang, Ji-Wei Ma, Shaoxiang Wang, Xiao Wang, Xueyun Zhong, Yu-Lin Wen, Jiecheng Ye |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Survival Population Apoptosis Pyrimidinones Biology Benzylisoquinolines 03 medical and health sciences chemistry.chemical_compound Cancer stem cell Cell Movement Neurosphere Cell Line Tumor Humans Viability assay education beta Catenin Cell Proliferation bcl-2-Associated X Protein education.field_of_study Glioma Cell cycle Bridged Bicyclo Compounds Heterocyclic Molecular biology Neural stem cell Tetrandrine Gene Expression Regulation Neoplastic 030104 developmental biology Oncology chemistry Cell culture Drug Resistance Neoplasm Cancer research Neoplastic Stem Cells Neoplasm Recurrence Local |
| Zdroj: | International journal of oncology. 50(1) |
| ISSN: | 1791-2423 |
| Popis: | Cancer stem cells (CSCs) in glioma are often responsible for relapse and resistance to therapy. The purpose of the present study was to confirm the self-renewal and migration inhibitory effects of tetrandrine (Tet), which is a compound extracted from the dried root of Stephania tetrandra S. Moore, toward glioma stem-like cells (GSLCs) and to examine the associated molecular mechanisms. Using a neurosphere culture technique, we enriched the GSLC population from the human glioblastoma cell lines U87 and U251. Cells were analyzed using cell counting kit-8 (CCK-8), western blotting, flow cytometry, transwell assay and immunofluorescence staining. GSLCs displayed properties of neural stem cells, including elevated expression of the cancer stem cell marker ALDH1 and β-catenin. We found that Tet treatment decreased sphere formation in GSLCs in a dose-dependent manner using tumor spheroid formation assay. The GSK3β inhibitor BIO maintained sphere formation and migration capacity in GSLCs, whereas the β-catenin/TCF transcription inhibitor ICG-001 decreased sphere formation and the migration capacity of GSLCs. The proportion of apoptotic GSLCs also increased in response to ICG-001 treatment. These results indicate that β-catenin activity is vital in maintaining neural stem cell traits of GSLCs. Tet inhibits cell viability, neurosphere formation and migration of GSLCs in vitro. Importantly, Tet treatment significantly repressed the nuclear translocation and expression of β-catenin and induced apoptosis in GSLCs, as indicated in part by the upregulation of Bax, the cleavage of PARP and the downregulation of Bcl-2. The present study demonstrates that the inhibition of β-catenin in CSCs by Tet could be an effective strategy for the treatment of glioma. |
| Databáze: | OpenAIRE |
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