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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

文献类型：期刊论文

作者Fang, Xin-Yi3; Zhang, Hai2; Zhao, Lin3; Tan, Shuai3; Ren, Qing-Cuo2; Wang, Lun1; Shen, Xiao-Fei3
刊名BIOCHIMIE
出版日期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
DOI10.1016/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
WOS记录号WOS:000443637700005
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
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_天然产物研究
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.

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来源：成都生物研究所

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