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

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资源类型：
Pubmed体系：
作者：
Xin-Yi Fang[a] ; Hai Zhang[b] ; Lin Zhao[a] ; Shuai Tan[a] ; Qing-Cuo Ren[b] ; Lun Wang[c] ; Xiao-Fei Shen[a] ;
机构： [a]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 [b]Chengdu University of Traditional Chinese Medicine, Chengdu, China [c]Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China
出处：
DOI： 10.1016/j.biochi.2018.06.018
ISSN：

关键词： 1b-hydroxyl-5a-chloro-8-epi-xanthatin Hepatocellular carcinoma Apoptosis Reactive oxygen species Glutathione MAPKs and JAK2/STAT3 cascades

摘要：
1β-hydroxyl-5α-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. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

基金：
This work was supported by grant from the Health and Family Planning Commission of Sichuan Province (17PJ485) and Science and Technology Program for Public Wellbeing of Chengdu (No. 2016-HM01-00457-SF).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类 | 3 区 生物
小类 | 3 区 生化与分子生物学
最新[2023]版：
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学
第一作者：
第一作者机构： [a]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
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Xin-Yi Fang,Hai Zhang,Lin Zhao,et al.A new xanthatin analogue 1β-hydroxyl-5α-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma.[J].Biochimie.2018,152:43-52.doi:10.1016/j.biochi.2018.06.018.
APA：
Xin-Yi Fang,Hai Zhang,Lin Zhao,Shuai Tan,Qing-Cuo Ren...&Xiao-Fei Shen.(2018).A new xanthatin analogue 1β-hydroxyl-5α-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma..Biochimie,152,
MLA：
Xin-Yi Fang,et al."A new xanthatin analogue 1β-hydroxyl-5α-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

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