Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells

The potential antitumor effects of sempervirine (SPV), an alkaloid compound derived from the traditional Chinese medicine Gelsemium elegans Benth., on different malignant tumors were described in detail. The impact of SPV on glioma cells and the basic atomic components remain uncertain. This study a...

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Autores principales: Gaopan Li, Yuhuan Zhong, Wenyi Wang, Xiaokang Jia, Huaichang Zhu, Wenwen Jiang, Yu Song, Wen Xu, Shuisheng Wu
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/cdb13bfbd7df4104b69455752577b71b
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spelling oai:doaj.org-article:cdb13bfbd7df4104b69455752577b71b2021-12-01T19:20:43ZSempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells1663-981210.3389/fphar.2021.770667https://doaj.org/article/cdb13bfbd7df4104b69455752577b71b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.770667/fullhttps://doaj.org/toc/1663-9812The potential antitumor effects of sempervirine (SPV), an alkaloid compound derived from the traditional Chinese medicine Gelsemium elegans Benth., on different malignant tumors were described in detail. The impact of SPV on glioma cells and the basic atomic components remain uncertain. This study aimed to investigate the activity of SPV in vitro and in vivo. The effect of SPV on the growth of human glioma cells was determined to explore three aspects, namely, cell cycle, cell apoptosis, and autophagy. In this study, glioma cells, U251 and U87 cells, and one animal model were used. Cells were treated with SPV (0, 1, 4, and 8 μM) for 48 h. The cell viability, cell cycle, apoptosis rate and autophagic flux were examined. Cell cycle, apoptotic, autophagy, and Akt/mTOR signal pathway-related proteins, such as CDK1, Cyclin B1, Beclin-1, p62, LC3, AKT, and mTOR were investigated by Western blot approach. As a result, cells induced by SPV led to G2/M phase arrest and apoptosis. SPV also promoted the effect of autophagic flux and accumulation of LC3B. SPV reduced the expression of p62 protein and induced the autophagic death of glioma cells. Furthermore, SPV downregulated the expressions of AKT and mTOR phosphorylated proteins in the mTOR signaling pathway, thereby affecting the onset of apoptosis and autophagy in U251 cells. In conclusion, SPV induced cellular G2/M phase arrest and blockade of the Akt/mTOR signaling pathway, thereby triggering apoptosis and cellular autophagy. The in vivo and in vitro studies confirmed that SPV inhibits the growth of glioma cancer.Gaopan LiYuhuan ZhongYuhuan ZhongWenyi WangXiaokang JiaXiaokang JiaHuaichang ZhuWenwen JiangYu SongWen XuWen XuShuisheng WuShuisheng WuFrontiers Media S.A.articlesempervirineapoptosisauto-phagosomegliomacell cycleTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic sempervirine
apoptosis
auto-phagosome
glioma
cell cycle
Therapeutics. Pharmacology
RM1-950
spellingShingle sempervirine
apoptosis
auto-phagosome
glioma
cell cycle
Therapeutics. Pharmacology
RM1-950
Gaopan Li
Yuhuan Zhong
Yuhuan Zhong
Wenyi Wang
Xiaokang Jia
Xiaokang Jia
Huaichang Zhu
Wenwen Jiang
Yu Song
Wen Xu
Wen Xu
Shuisheng Wu
Shuisheng Wu
Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells
description The potential antitumor effects of sempervirine (SPV), an alkaloid compound derived from the traditional Chinese medicine Gelsemium elegans Benth., on different malignant tumors were described in detail. The impact of SPV on glioma cells and the basic atomic components remain uncertain. This study aimed to investigate the activity of SPV in vitro and in vivo. The effect of SPV on the growth of human glioma cells was determined to explore three aspects, namely, cell cycle, cell apoptosis, and autophagy. In this study, glioma cells, U251 and U87 cells, and one animal model were used. Cells were treated with SPV (0, 1, 4, and 8 μM) for 48 h. The cell viability, cell cycle, apoptosis rate and autophagic flux were examined. Cell cycle, apoptotic, autophagy, and Akt/mTOR signal pathway-related proteins, such as CDK1, Cyclin B1, Beclin-1, p62, LC3, AKT, and mTOR were investigated by Western blot approach. As a result, cells induced by SPV led to G2/M phase arrest and apoptosis. SPV also promoted the effect of autophagic flux and accumulation of LC3B. SPV reduced the expression of p62 protein and induced the autophagic death of glioma cells. Furthermore, SPV downregulated the expressions of AKT and mTOR phosphorylated proteins in the mTOR signaling pathway, thereby affecting the onset of apoptosis and autophagy in U251 cells. In conclusion, SPV induced cellular G2/M phase arrest and blockade of the Akt/mTOR signaling pathway, thereby triggering apoptosis and cellular autophagy. The in vivo and in vitro studies confirmed that SPV inhibits the growth of glioma cancer.
format article
author Gaopan Li
Yuhuan Zhong
Yuhuan Zhong
Wenyi Wang
Xiaokang Jia
Xiaokang Jia
Huaichang Zhu
Wenwen Jiang
Yu Song
Wen Xu
Wen Xu
Shuisheng Wu
Shuisheng Wu
author_facet Gaopan Li
Yuhuan Zhong
Yuhuan Zhong
Wenyi Wang
Xiaokang Jia
Xiaokang Jia
Huaichang Zhu
Wenwen Jiang
Yu Song
Wen Xu
Wen Xu
Shuisheng Wu
Shuisheng Wu
author_sort Gaopan Li
title Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells
title_short Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells
title_full Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells
title_fullStr Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells
title_full_unstemmed Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells
title_sort sempervirine mediates autophagy and apoptosis via the akt/mtor signaling pathways in glioma cells
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/cdb13bfbd7df4104b69455752577b71b
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