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

Content Provider	Springer Nature Link
Author	Wu, Ning Liu, Jia Zhao, Xiangzhong Yan, Zhiyong Jiang, Bo Wang, Lijun Cao, Shousong Shi, Dayong Lin, Xiukun
Copyright Year	2015
Abstract	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 × 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 × 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.
Starting Page	9667
Ending Page	9676
Page Count	10
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	36
Issue Number	12
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-07-07
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Cardamonin Glioblastoma stem cell STAT3 Apoptosis Temozolomide Self-renewal Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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