Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells

	Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells
	Wu, Ning 1; Liu, Jia 2; Zhao, Xiangzhong 3; Yan, Zhiyong 3; Jiang, Bo 1; Wang, Lijun 1; Cao, Shousong 4; Shi, Dayong 1; Lin, Xiukun 5
刊名	TUMOR BIOLOGY
	2015-12-01
卷号	36 期号:12 页码:9667-9676
关键词	Cardamonin Glioblastoma stem cell STAT3 Apoptosis Temozolomide Self-renewal
英文摘要	Glioblastoma stem cells (GSCs) are the initiating cells in glioblastoma multiforme (GBM) and contribute to the resistance of GBM to chemotherapy and radiation. In the present study, we investigated the effects of cardamonin (3,4,2,4-tetrahydroxychalcone) on the self-renewal and apoptosis of GSCs, and if its action is associated with signal transducer and activator of transcription 3 (STAT3) pathway. CD133(+) GSCs, a kind of GSCs line, was established from human glioblastoma tissues. Cardamonin inhibited the proliferation and induced apoptosis in CD133+ GSCs. The proapoptotic effects of temozolomide (TMZ) were further enhanced by cardamonin in CD133+ GSCs and U87 cells in vitro. For in vivo study, injection of 5 x 10(5) cells of CD133+ GSCs subcutaneously (s.c.) into nude mice, 100 % of large tumors were developed within 8 weeks in all mice; in contrast, only one out of five mice developed a small tumor when 5 x 10(5) cells of CD133(-) GMBs cells were injected. Cardamonin also inhibited STAT3 activation by luciferase assay and suppressed the expression of the downstream genes of STAT3, such as Bcl-XL, Bcl-2, Mcl-1, survivin, and VEGF. Furthermore, cardamonin locked nuclear translocation and dimerization of STAT3 in CD133(+) GSCs. Docking analysis confirmed that cardamonin molecule was successfully docked into the active sites of STAT3 with a highly favorable binding energy of -10.78 kcal/mol. The study provides evidence that cardamonin is a novel inhibitor of STAT3 and has the potential to be developed as a new anticancer agent targeting GSCs. This study also reveals that targeting STAT3 signal pathway is an important strategy for the treatment of human GBM.
收录类别	SCI
语种	英语
WOS记录号	WOS:000367329300062
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/86658]
专题	海洋研究所_海洋生物技术研发中心
作者单位	1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China 2.Qingdao Univ, Coll Med, Qingdao 266021, Peoples R China 3.Qingdao Med Univ, Affiliated Hosp, Qingdao 266070, Peoples R China 4.Chifeng Saliont Pharmaceut Co Ltd, Chifeng, Mongolia Autono, Peoples R China 5.Capital Med Univ, Dept Pharmacol, Beijing 100069, Peoples R China
推荐引用方式 GB/T 7714	Wu, Ning,Liu, Jia,Zhao, Xiangzhong,et al. Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells[J]. TUMOR BIOLOGY,2015,36(12):9667-9676.
APA	Wu, Ning.,Liu, Jia.,Zhao, Xiangzhong.,Yan, Zhiyong.,Jiang, Bo.,...&Lin, Xiukun.(2015).Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells.TUMOR BIOLOGY,36(12),9667-9676.
MLA	Wu, Ning,et al."Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells".TUMOR BIOLOGY 36.12(2015):9667-9676.