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Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP
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 apo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892302/ https://www.ncbi.nlm.nih.gov/pubmed/29780826 http://dx.doi.org/10.1155/2018/6165192 |
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author | Bai, Zhuan-Li Tay, Vincent Guo, Shu-Zhong Ren, Juan Shu, Mao-Guo |
author_facet | Bai, Zhuan-Li Tay, Vincent Guo, Shu-Zhong Ren, Juan Shu, Mao-Guo |
author_sort | Bai, Zhuan-Li |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5892302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-58923022018-05-20 Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP Bai, Zhuan-Li Tay, Vincent Guo, Shu-Zhong Ren, Juan Shu, Mao-Guo Biomed Res Int Research Article 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. Hindawi 2018-03-26 /pmc/articles/PMC5892302/ /pubmed/29780826 http://dx.doi.org/10.1155/2018/6165192 Text en Copyright © 2018 Zhuan-Li Bai et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Bai, Zhuan-Li Tay, Vincent Guo, Shu-Zhong Ren, Juan Shu, Mao-Guo Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP |
title | Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP |
title_full | Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP |
title_fullStr | Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP |
title_full_unstemmed | Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP |
title_short | Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP |
title_sort | silibinin induced human glioblastoma cell apoptosis concomitant with autophagy through simultaneous inhibition of mtor and yap |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892302/ https://www.ncbi.nlm.nih.gov/pubmed/29780826 http://dx.doi.org/10.1155/2018/6165192 |
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