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Cardamonin induces apoptosis by suppressing STAT3 signaling pathway in glioblastoma stem cells
Wu, Ning1; Liu, Jia2; Zhao, Xiangzhong3; Yan, Zhiyong3; Jiang, Bo1; Wang, Lijun1; Cao, Shousong4; Shi, Dayong1; Lin, Xiukun5
2015-12-01
发表期刊TUMOR BIOLOGY
卷号36期号:12页码:9667-9676
文章类型Article
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.
关键词Cardamonin Glioblastoma Stem Cell Stat3 Apoptosis Temozolomide Self-renewal
DOI10.1007/s13277-015-3673-y
收录类别SCI
语种英语
WOS记录号WOS:000367329300062
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被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.qdio.ac.cn/handle/337002/86658
专题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
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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.
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