Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer

Objective: Costunolide (Cos) is a sesquiterpene lactone extracted from chicory. Although it possesses anti-tumor effects, the underlying molecular mechanism against gastric cancer cells remains unclear. This study aimed to explore the effect and potential mechanism of Cos on gastric cancer.Methods:...

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Autores principales:	Cuixiang Xu, Xiaoyan Huang, Xiaohua Lei, Zhankui Jin, Min Wu, Xiao Liu, Yubin Huang, Xiangrong Zhao, Yue Xiong, Jingying Sun, Xianglong Duan, Jianhua Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	costunolide apoptosis autophagy ROS Akt/GSK3β gastric cancer Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9bde2ec7c0cb479ca087c522191de5d5
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spelling	oai:doaj.org-article:9bde2ec7c0cb479ca087c522191de5d52021-11-12T07:09:28ZCostunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer2296-634X10.3389/fcell.2021.722734https://doaj.org/article/9bde2ec7c0cb479ca087c522191de5d52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.722734/fullhttps://doaj.org/toc/2296-634XObjective: Costunolide (Cos) is a sesquiterpene lactone extracted from chicory. Although it possesses anti-tumor effects, the underlying molecular mechanism against gastric cancer cells remains unclear. This study aimed to explore the effect and potential mechanism of Cos on gastric cancer.Methods: The effect of Cos on HGC-27 and SNU-1 proliferation was detected by CCK-8 and clone formation assay. The changes in cell apoptosis were determined using Hoechst 33258 and tunel staining. The morphology of autophagy was analyzed by autophagosomes with the electron microscope and LC3-immunofluorescence with the confocal microscope. The related protein levels of the cell cycle, apoptosis, autophagy and AKT/GSK3β pathway were determined by Western blot. The anti-tumor activity of Cos was evaluated by subcutaneously xenotransplanting HGC-27 into Balb/c nude mice. The Ki67 and P-AKT levels were examined by immunohistochemistry.Results: Cos significantly inhibited HGC-27 and SNU-1 growth and induced cell cycle arrest in the G2/M phase. Cos activated intrinsic apoptosis and autophagy through promoting cellular reactive oxygen species (ROS) levels and inhibiting the ROS-AKT/GSK3β signaling pathway. Moreover, preincubating gastric carcinoma cells with 3-methyladenine (3-MA), a cell-autophagy inhibitor, significantly alleviated the effects of Cos in inducing cell apoptosis.Conclusion: Cos induced apoptosis of gastric carcinoma cells via promoting ROS and inhibiting AKT/GSK3β pathway and activating pro-death cell autophagy, which may be an effective strategy to treat gastric cancer.Cuixiang XuXiaoyan HuangXiaohua LeiZhankui JinMin WuXiao LiuXiao LiuYubin HuangYubin HuangXiangrong ZhaoYue XiongJingying SunXianglong DuanJianhua WangFrontiers Media S.A.articlecostunolideapoptosisautophagyROSAkt/GSK3βgastric cancerBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	costunolide apoptosis autophagy ROS Akt/GSK3β gastric cancer Biology (General) QH301-705.5
spellingShingle	costunolide apoptosis autophagy ROS Akt/GSK3β gastric cancer Biology (General) QH301-705.5 Cuixiang Xu Xiaoyan Huang Xiaohua Lei Zhankui Jin Min Wu Xiao Liu Xiao Liu Yubin Huang Yubin Huang Xiangrong Zhao Yue Xiong Jingying Sun Xianglong Duan Jianhua Wang Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer
description	Objective: Costunolide (Cos) is a sesquiterpene lactone extracted from chicory. Although it possesses anti-tumor effects, the underlying molecular mechanism against gastric cancer cells remains unclear. This study aimed to explore the effect and potential mechanism of Cos on gastric cancer.Methods: The effect of Cos on HGC-27 and SNU-1 proliferation was detected by CCK-8 and clone formation assay. The changes in cell apoptosis were determined using Hoechst 33258 and tunel staining. The morphology of autophagy was analyzed by autophagosomes with the electron microscope and LC3-immunofluorescence with the confocal microscope. The related protein levels of the cell cycle, apoptosis, autophagy and AKT/GSK3β pathway were determined by Western blot. The anti-tumor activity of Cos was evaluated by subcutaneously xenotransplanting HGC-27 into Balb/c nude mice. The Ki67 and P-AKT levels were examined by immunohistochemistry.Results: Cos significantly inhibited HGC-27 and SNU-1 growth and induced cell cycle arrest in the G2/M phase. Cos activated intrinsic apoptosis and autophagy through promoting cellular reactive oxygen species (ROS) levels and inhibiting the ROS-AKT/GSK3β signaling pathway. Moreover, preincubating gastric carcinoma cells with 3-methyladenine (3-MA), a cell-autophagy inhibitor, significantly alleviated the effects of Cos in inducing cell apoptosis.Conclusion: Cos induced apoptosis of gastric carcinoma cells via promoting ROS and inhibiting AKT/GSK3β pathway and activating pro-death cell autophagy, which may be an effective strategy to treat gastric cancer.
format	article
author	Cuixiang Xu Xiaoyan Huang Xiaohua Lei Zhankui Jin Min Wu Xiao Liu Xiao Liu Yubin Huang Yubin Huang Xiangrong Zhao Yue Xiong Jingying Sun Xianglong Duan Jianhua Wang
author_facet	Cuixiang Xu Xiaoyan Huang Xiaohua Lei Zhankui Jin Min Wu Xiao Liu Xiao Liu Yubin Huang Yubin Huang Xiangrong Zhao Yue Xiong Jingying Sun Xianglong Duan Jianhua Wang
author_sort	Cuixiang Xu
title	Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer
title_short	Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer
title_full	Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer
title_fullStr	Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer
title_full_unstemmed	Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer
title_sort	costunolide-induced apoptosis via promoting the reactive oxygen species and inhibiting akt/gsk3β pathway and activating autophagy in gastric cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/9bde2ec7c0cb479ca087c522191de5d5
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Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer

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