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学科主题药学
A sesquiterpene lactone antrocin from Antrodia camphorata negatively modulates JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis in lung cancer cells
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
2013-12-01
DOI10.1093/carcin/bgt255
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
WOS记录号WOS:000328278900026
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
资助机构National Science Council of Taiwan ; National Research Program for Biopharmaceuticals of Taiwan ; Natural Science Foundation of China
引用统计
被引频次:32[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52251
专题北京大学药学院_天然药物学系
北京大学精神卫生研究所_药房
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
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GB/T 7714
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.
APA Yeh, Chi-Tai.,Huang, Wen-Chien.,Rao, Yerra Koteswara.,Ye, Min.,Lee, Wei-Hwa.,...&Tzeng, Yew-Min.(2013).A sesquiterpene lactone antrocin from Antrodia camphorata negatively modulates JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis in lung cancer cells.CARCINOGENESIS,34(12),2918-2928.
MLA Yeh, Chi-Tai,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".CARCINOGENESIS 34.12(2013):2918-2928.
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