Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP
| Autor: | Shu-Zhong Guo, Juan Ren, Vincent Shian-Chao Tay, Maoguo Shu, Zhuan-Li Bai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Article Subject lcsh:Medicine Silibinin Caspase 3 Apoptosis General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Cell Line Tumor Flavonolignan Autophagy Humans PI3K/AKT/mTOR pathway Adaptor Proteins Signal Transducing General Immunology and Microbiology TOR Serine-Threonine Kinases lcsh:R YAP-Signaling Proteins General Medicine Phosphoproteins 030104 developmental biology chemistry Cell culture 030220 oncology & carcinogenesis Silybin Cancer research Glioblastoma Silymarin Transcription Factors Research Article |
| Zdroj: | BioMed Research International BioMed Research International, Vol 2018 (2018) |
| ISSN: | 2314-6133 |
| DOI: | 10.1155/2018/6165192 |
| Popis: | Silibinin, also known as silybin, is the major flavonolignan isolated from Silybum marianum. Although previous reports demonstrated that silibinin exhibits significant tumor suppressor activities in various cancers by promoting cell apoptosis, it was also shown to trigger autophagy to counteract apoptosis induced by exogenous stresses in several types of cells. However, there is no report to address the role of silibinin induced autophagy in human A172 and SR glioblastoma cells. Our study showed that silibinin treatment not only inhibited the metabolic activities of glioblastoma cells but also promoted their apoptosis through the regulation of caspase 3 and PARP-1 in concentration- and time-dependent manners. Meanwhile, silibinin induced autophagy through upregulation of microtubule-associated protein a light chain 3- (LC3-) II. And autophagy inhibition with chloroquine, a lysosomotropic agent, significantly enhanced silibinin induced glioblastoma cell apoptosis. Moreover, silibinin dose-dependently downregulated the phosphorylation levels of mTOR at Ser-2448, p70S6K at Thr-389, and 4E-BP1 at Thr-37/46. Furthermore, the expression of YAP, the downstream effector of Hippo signal pathway, was also suppressed by silibinin. These results suggested that silibinin induced glioblastoma cell apoptosis concomitant with autophagy which might be due to simultaneous inhibition of mTOR and YAP and silibinin induced autophagy exerted a protective role against cell apoptosis in both A172 and SR cells. |
| Databáze: | OpenAIRE |
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