A sesquiterpene lactone antrocin from Antrodia camphorata negatively   modulates JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis   in lung cancer cells

doi:10.1093/carcin/bgt255

CORC > 北京大学 > 化学与分子工程学院

	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-Tai ; Huang, Wen-Chien ; Rao, Yerra Koteswara ; Ye, Min ; Lee, Wei-Hwa ; Wang, Liang-Shun ; Tzeng, David T. W. ; Wu, Chih-Hsiung ; Shieh, Yi-Shing ; Huang, Chi-Ying F. ; Chen, Yu-Jen ; Hsiao, Michael ; Wu, Alexander T. H. ; Yang, Zhen ; Tzeng, Yew-Min
刊名	carcinogenesis
	2013
关键词	POTENT ANTITUMOR-ACTIVITY STAT3 EXPRESSION IN-VITRO PATHWAY ACTIVATION ANGIOGENESIS PROGRESSION INHIBITORS CARCINOMA GROWTH
DOI	10.1093/carcin/bgt255
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.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000328278900026&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Oncology; SCI(E); 21; ARTICLE; 12; 2918-2928; 34
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/390737]
专题	化学与分子工程学院
推荐引用方式 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.
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.
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 (2013).