Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway

Abstract Background Gastric cancer is a common gastrointestinal cancer and currently has the third-highest mortality rate. Research shows that the natural compound narciclasine has a variety of biological activities. The present study aimed to investigate the effect of narciclasine on gastric cancer...

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Autores principales:	Yunfeng Yuan, Xue He, Xiang Li, Yan Liu, Yueliang Tang, Huiming Deng, Xinyuan Shi
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Narciclasine Gastric cancer Autophagy Apoptosis Akt/mTOR pathway Therapeutics. Pharmacology RM1-950 Toxicology. Poisons RA1190-1270
Acceso en línea:	https://doaj.org/article/bab1342bc1fa4187a1cb4462135cc6dc
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spelling	oai:doaj.org-article:bab1342bc1fa4187a1cb4462135cc6dc2021-11-14T12:16:59ZNarciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway10.1186/s40360-021-00537-32050-6511https://doaj.org/article/bab1342bc1fa4187a1cb4462135cc6dc2021-11-01T00:00:00Zhttps://doi.org/10.1186/s40360-021-00537-3https://doaj.org/toc/2050-6511Abstract Background Gastric cancer is a common gastrointestinal cancer and currently has the third-highest mortality rate. Research shows that the natural compound narciclasine has a variety of biological activities. The present study aimed to investigate the effect of narciclasine on gastric cancer cells and its molecular mechanisms and determine whether this compound could be a novel therapy for gastric cancer. Methods MTT and clone assays were employed to detect the proliferation of gastric cancer cells. The cell apoptosis was detected by flow cytometry. The formation of autophagosomes and autophagosomal lysosomes was observed by transmission electron microscopy and laser confocal scanning microscopy. Western blotting was used to detect the expression of apoptosis, autophagy and Akt/mTOR pathway-related proteins. Results In this study, we found that narciclasine could inhibit the proliferation of gastric cancer cells and promote apoptosis in gastric cancer cells. Further experiments showed that narciclasine promoted the levels of autophagy proteins LC3-II, Atg-5 and Beclin-1, reduced the expression of the autophagy transporter p62, and increased autophagic flux. By using the autophagy inhibitors 3-MA and CQ, it was shown that narciclasine could induce autophagy-mediated apoptosis in gastric cancer cells. Finally, we found that narciclasine had no significant effects on the total content of Akt and mTOR in gastric cancer cells, and it involved autophagy in gastric cancer cells by reducing the phosphorylation level of p-Akt and p-mTOR. Conclusions Narciclasine can induce autophagy-dependent apoptosis in gastric cancer cells by inhibiting the phosphorylation level of Akt/mTOR and thus reduce the proliferation of gastric cancer cells.Yunfeng YuanXue HeXiang LiYan LiuYueliang TangHuiming DengXinyuan ShiBMCarticleNarciclasineGastric cancerAutophagyApoptosisAkt/mTOR pathwayTherapeutics. PharmacologyRM1-950Toxicology. PoisonsRA1190-1270ENBMC Pharmacology and Toxicology, Vol 22, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Narciclasine Gastric cancer Autophagy Apoptosis Akt/mTOR pathway Therapeutics. Pharmacology RM1-950 Toxicology. Poisons RA1190-1270
spellingShingle	Narciclasine Gastric cancer Autophagy Apoptosis Akt/mTOR pathway Therapeutics. Pharmacology RM1-950 Toxicology. Poisons RA1190-1270 Yunfeng Yuan Xue He Xiang Li Yan Liu Yueliang Tang Huiming Deng Xinyuan Shi Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway
description	Abstract Background Gastric cancer is a common gastrointestinal cancer and currently has the third-highest mortality rate. Research shows that the natural compound narciclasine has a variety of biological activities. The present study aimed to investigate the effect of narciclasine on gastric cancer cells and its molecular mechanisms and determine whether this compound could be a novel therapy for gastric cancer. Methods MTT and clone assays were employed to detect the proliferation of gastric cancer cells. The cell apoptosis was detected by flow cytometry. The formation of autophagosomes and autophagosomal lysosomes was observed by transmission electron microscopy and laser confocal scanning microscopy. Western blotting was used to detect the expression of apoptosis, autophagy and Akt/mTOR pathway-related proteins. Results In this study, we found that narciclasine could inhibit the proliferation of gastric cancer cells and promote apoptosis in gastric cancer cells. Further experiments showed that narciclasine promoted the levels of autophagy proteins LC3-II, Atg-5 and Beclin-1, reduced the expression of the autophagy transporter p62, and increased autophagic flux. By using the autophagy inhibitors 3-MA and CQ, it was shown that narciclasine could induce autophagy-mediated apoptosis in gastric cancer cells. Finally, we found that narciclasine had no significant effects on the total content of Akt and mTOR in gastric cancer cells, and it involved autophagy in gastric cancer cells by reducing the phosphorylation level of p-Akt and p-mTOR. Conclusions Narciclasine can induce autophagy-dependent apoptosis in gastric cancer cells by inhibiting the phosphorylation level of Akt/mTOR and thus reduce the proliferation of gastric cancer cells.
format	article
author	Yunfeng Yuan Xue He Xiang Li Yan Liu Yueliang Tang Huiming Deng Xinyuan Shi
author_facet	Yunfeng Yuan Xue He Xiang Li Yan Liu Yueliang Tang Huiming Deng Xinyuan Shi
author_sort	Yunfeng Yuan
title	Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway
title_short	Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway
title_full	Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway
title_fullStr	Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway
title_full_unstemmed	Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway
title_sort	narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the akt/mtor signaling pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/bab1342bc1fa4187a1cb4462135cc6dc
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Narciclasine induces autophagy-mediated apoptosis in gastric cancer cells through the Akt/mTOR signaling pathway

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