北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学药学院  > 天然药物学系  > 期刊论文
学科主题: 药学
题名:
A sesquiterpene lactone antrocin from Antrodia camphorata negatively modulates JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis in lung cancer cells
作者: Yeh, Chi-Tai1,2,3; Huang, Wen-Chien4,5; Rao, Yerra Koteswara6; Ye, Min7; Lee, Wei-Hwa8; Wang, Liang-Shun1,9; Tzeng, David T. W.10; Wu, Chih-Hsiung2; Shieh, Yi-Shing11; Huang, Chi-Ying F.12; Chen, Yu-Jen13; Hsiao, Michael14; Wu, Alexander T. H.15,16; Yang, Zhen17; Tzeng, Yew-Min6
刊名: CARCINOGENESIS
发表日期: 2013-12-01
DOI: 10.1093/carcin/bgt255
卷: 34, 期:12, 页:2918-2928
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: POTENT ANTITUMOR-ACTIVITY ; STAT3 EXPRESSION ; IN-VITRO ; PATHWAY ; ACTIVATION ; ANGIOGENESIS ; PROGRESSION ; INHIBITORS ; CARCINOMA ; GROWTH
英文摘要:

Lung cancer is the leading cause of cancer deaths worldwide and current therapies fail to treat this disease in majority of cases. Antrodia camphorata is a medicinal mushroom being widely used as food dietary supplement for cancer prevention. The sesquiterpene lactone antrocin is the most potent among >100 secondary metabolites isolated from A. camphorata. However, the molecular mechanisms of antrocin-mediated anticancer effects remain unclear. In this study, we found that antrocin inhibited cell proliferation in two non-small-cell lung cancer cells, namely H441 (wild-type epidermal growth factor receptor, IC50 = 0.75 mu M) and H1975 (gefitnib-resistant mutant T790M, IC50 = 0.83 mu M). Antrocin dose dependently suppressed colony formation and induced apoptosis as evidenced by activated caspase-3 and increased Bax/Bcl2 ratio. Gene profiling studies indicated that antrocin downregulated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. We further demonstrated that antrocin suppressed both constitutively activated and interleukin 6-induced STAT3 phosphorylation and its subsequent nuclear translocation. Such inhibition is found to be achieved through the suppression of JAK2 and interaction between STAT3 and extracellular signal-regulated kinase. Additionally, antrocin increased microRNA let-7c expression and suppressed STAT signaling. The combination of antrocin and JAK2/STAT3 gene silencing significantly increased apoptosis in H441 cells. Such dual interruption of JAK2 and STAT3 pathways also induced downregulation of antiapoptotic protein mcl-1 and increased caspase-3 expression. In vivo intraperitoneal administration of antrocin significantly suppressed the growth of lung cancer tumor xenografts. Our results indicate that antrocin may be a potential therapeutic agent for human lung cancer cells through constitutive inhibition of JAK2/STAT3 pathway.

语种: 英语
所属项目编号: 100-2113-M-324-001-MY3 ; 101-2811-M-324-001 ; 99-2628-B-038-101-MY3 ; 100-2313-B-038-001-MY3 ; 101-2325-B-038-005 ; 102TMU-SHH-02 ; 100-2325-B-010-009 ; 101CGH-TMU-06 ; 100TMU-TMUH-09 ; 101TMU-SHH-05 ; 91013004
项目资助者: National Science Council of Taiwan ; National Research Program for Biopharmaceuticals of Taiwan ; Natural Science Foundation of China
WOS记录号: WOS:000328278900026
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52251
Appears in Collections:北京大学药学院_天然药物学系_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Mackay Mem Hosp, Dept Thorac Surg, Taipei 10449, Taiwan
2.Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan
3.Taipei Med Univ, Grad Inst Clin Med, Taipei 11031, Taiwan
4.Natl Def Med Ctr, Grad Inst Med Sci, Taipei 11490, Taiwan
5.Taipei Med Univ, Dept Surg, Shuang Ho Hosp, Taipei 23561, Taiwan
6.Natl Yang Ming Univ, Inst Tradit Med, Sch Med, Taipei 11221, Taiwan
7.Chaoyang Univ Technol, Inst Biochem Sci & Technol, Taichung 41349, Taiwan
8.Peking Univ, Dept Nat Med, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
9.Taipei Med Univ, Dept Pathol, Shuang Ho Hosp, Taipei 23561, Taiwan
10.Taipei Med Univ, Shuang Ho Hosp, Div Thorac Surg, Dept Surg, Taipei 23561, Taiwan
11.Natl Chung Hsing Univ, Inst Genom & Bioinformat, Taichung 40227, Taiwan
12.Triserv Gen Hosp, Dept Oral Diag, Natl Def Med Ctr, Taipei 11490, Taiwan
13.Natl Yang Ming Univ, Inst Biopharmaceut Sci, Taipei 11221, Taiwan
14.Natl Yang Ming Univ, Sch Med, Inst Tradit Med, Taipei 11221, Taiwan
15.Taipei Med Univ, Ph D Program Translat Med, Coll Med Sci & Technol, Taipei 11031, Taiwan
16.Taipei Med Univ Hosp, Translat Res Lab, Ctr Canc, Taipei 11031, Taiwan
17.Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China

Recommended Citation:
Yeh, Chi-Tai,Huang, Wen-Chien,Rao, Yerra Koteswara,et al. A sesquiterpene lactone antrocin from Antrodia camphorata negatively modulates JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis in lung cancer cells[J]. CARCINOGENESIS,2013,34(12):2918-2928.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Yeh, Chi-Tai]'s Articles
[Huang, Wen-Chien]'s Articles
[Rao, Yerra Koteswara]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Yeh, Chi-Tai]‘s Articles
[Huang, Wen-Chien]‘s Articles
[Rao, Yerra Koteswara]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace