Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway

Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the Chinese medicinal plant, Sinomenium acutum, showed that it had inhibitory effects on several kinds of cance...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiangjin Zheng, Wan Li, Huanli Xu, Jinyi Liu, Liwen Ren, Yihui Yang, Sha Li, Jinhua Wang, Tengfei Ji, Guanhua Du
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	SW33 GBM G2/M phase Apoptosis Autophagy mTOR Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/8175938ecdce443c9578f9957722b824
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8175938ecdce443c9578f9957722b824
record_format	dspace
spelling	oai:doaj.org-article:8175938ecdce443c9578f9957722b8242021-12-02T05:01:24ZSinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway2211-383510.1016/j.apsb.2021.05.027https://doaj.org/article/8175938ecdce443c9578f9957722b8242021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211383521002069https://doaj.org/toc/2211-3835Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the Chinese medicinal plant, Sinomenium acutum, showed that it had inhibitory effects on several kinds of cancer. Here, we synthesized a sinomenine derivative, sino-wcj-33 (SW33), tested it for antitumor activity on GBM and explored the underlying mechanism. SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells. It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis. Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body. SW33 also induced autophagy through the PI3K/AKT/mTOR and AMPK/mTOR pathways. Thus, SW33 appears to be a promising drug for treating GBM effectively and safely.Xiangjin ZhengWan LiHuanli XuJinyi LiuLiwen RenYihui YangSha LiJinhua WangTengfei JiGuanhua DuElsevierarticleSW33GBMG2/M phaseApoptosisAutophagymTORTherapeutics. PharmacologyRM1-950ENActa Pharmaceutica Sinica B, Vol 11, Iss 11, Pp 3465-3480 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SW33 GBM G2/M phase Apoptosis Autophagy mTOR Therapeutics. Pharmacology RM1-950
spellingShingle	SW33 GBM G2/M phase Apoptosis Autophagy mTOR Therapeutics. Pharmacology RM1-950 Xiangjin Zheng Wan Li Huanli Xu Jinyi Liu Liwen Ren Yihui Yang Sha Li Jinhua Wang Tengfei Ji Guanhua Du Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway
description	Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the Chinese medicinal plant, Sinomenium acutum, showed that it had inhibitory effects on several kinds of cancer. Here, we synthesized a sinomenine derivative, sino-wcj-33 (SW33), tested it for antitumor activity on GBM and explored the underlying mechanism. SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells. It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis. Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body. SW33 also induced autophagy through the PI3K/AKT/mTOR and AMPK/mTOR pathways. Thus, SW33 appears to be a promising drug for treating GBM effectively and safely.
format	article
author	Xiangjin Zheng Wan Li Huanli Xu Jinyi Liu Liwen Ren Yihui Yang Sha Li Jinhua Wang Tengfei Ji Guanhua Du
author_facet	Xiangjin Zheng Wan Li Huanli Xu Jinyi Liu Liwen Ren Yihui Yang Sha Li Jinhua Wang Tengfei Ji Guanhua Du
author_sort	Xiangjin Zheng
title	Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway
title_short	Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway
title_full	Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway
title_fullStr	Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway
title_full_unstemmed	Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway
title_sort	sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by pi3k/akt/mtor and ampk/mtor pathway
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/8175938ecdce443c9578f9957722b824
work_keys_str_mv	AT xiangjinzheng sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway AT wanli sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway AT huanlixu sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway AT jinyiliu sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway AT liwenren sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway AT yihuiyang sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway AT shali sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway AT jinhuawang sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway AT tengfeiji sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway AT guanhuadu sinomenineesterderivativeinhibitsglioblastomabyinducingmitochondriadependentapoptosisandautophagybypi3kaktmtorandampkmtorpathway
_version_	1718400839648804864

Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway

Ejemplares similares