A new xanthatin analogue 1 beta-hydroxyl-5 alpha-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma

doi:10.1016/j.biochi.2018.06.018

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	A new xanthatin analogue 1 beta-hydroxyl-5 alpha-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma
	Fang, Xin-Yi 3; Zhang, Hai 2; Zhao, Lin 3; Tan, Shuai 3; Ren, Qing-Cuo 2; Wang, Lun 1; Shen, Xiao-Fei 3
刊名	BIOCHIMIE
	2018-09-01
卷号	152 期号:2018 页码:43-52
关键词	1 beta-hydroxyl-5 alpha-chloro-8-epi-xanthatin Hepatocellular carcinoma Apoptosis Reactive oxygen species Glutathione MAPKs and JAK2/STAT3 cascades
ISSN号	0300-9084
DOI	10.1016/j.biochi.2018.06.018
产权排序	3
文献子类	Article
英文摘要	1 beta-hydroxyl-5 alpha-chloro-8-epi-xanthatin (XTT), a sesquiterpene lactone isolated from Xanthium sibiricum, possessed potent cytotoxicity on cancer cells in vitro. The objective of this study was to investigate the anti-tumor effect and underlying mechanisms of XTT on human hepatocellular carcinoma (HCC). Firstly, XTT inhibited the cell growth and induced apoptosis in human HCC cells, which was associated with the induction of Bax and cleaved-caspase-3, inhibition of Bcl-2 and survivin expression. Importantly, XTT induced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), and depletion of glutathione (GSH) in HCC cells through covalently modification of GSH. Furthermore, XTT caused obvious activation of extracellular regulated protein kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) and inactivation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) in HCC cells. ROS scavenger N-acetyl cysteine abrogated the effects of XTT on ERK/p38 MAPK activation and JAK2/STAT3 inhibition, and rescued HCC cells from XTT-induced apoptosis. Additionally, inhibitors of ERK/p38 MAPKs or activator of JAK2/STAT3 partially abolished XTT-mediated effect. In summary, XTT inhibited cell growth and induced apoptosis in HCC cells through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition by GSH depletion. These findings also show the therapeutic potential of XTT in HCC. (C) 2018 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
学科主题	Biochemistry ; Biophysics
URL标识	查看原文
WOS关键词	CANCER-CELLS ; PATHWAYS ; STAT3 ; MECHANISMS ; AUTOPHAGY ; STRESS ; DEATH
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000443637700005
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/30161]
专题	国家天然药物工程技术研究中心
作者单位	1.Chinese Acad Sci, Chengdu Inst Biol, Chengdu, Sichuan, Peoples R China 2.Chengdu Univ Tradit Chinese Med, Chengdu, Sichuan, Peoples R China; 3.Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China;
推荐引用方式 GB/T 7714	Fang, Xin-Yi,Zhang, Hai,Zhao, Lin,et al. A new xanthatin analogue 1 beta-hydroxyl-5 alpha-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma[J]. BIOCHIMIE,2018,152(2018):43-52.
APA	Fang, Xin-Yi.,Zhang, Hai.,Zhao, Lin.,Tan, Shuai.,Ren, Qing-Cuo.,...&Shen, Xiao-Fei.(2018).A new xanthatin analogue 1 beta-hydroxyl-5 alpha-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma.BIOCHIMIE,152(2018),43-52.
MLA	Fang, Xin-Yi,et al."A new xanthatin analogue 1 beta-hydroxyl-5 alpha-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma".BIOCHIMIE 152.2018(2018):43-52.