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• W2253992326 abstract "// Ling-Mei Kong 1, 2 , Tao Feng 1 , Yuan-Yuan Wang 3 , Xing-Yao Li 1, 4 , Zhen-Nan Ye 1, 2 , Tao An 1, 2 , Chen Qing 5 , Xiao-Dong Luo 1 , Yan Li 1 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China 2 University of the Chinese Academy of Sciences, Beijing 100049, China 3 Harbin Institute of Technology (Weihai), Weihai 264209, China 4 Present address: Georgia Regents University Health Sciences Campus, Augusta, Georgia 30912, USA 5 Kunming Medical University, Kunming 650500, China Correspondence to: Yan Li, e-mail: liyanb@mail.kib.ac.cn Xiao-Dong Luo, e-mail: xdluo@mail.kib.ac.cn Keywords: Bisleuconothine A, inhibitor, Wnt signaling, colorectal cancer cells Received: August 26, 2015      Accepted: January 23, 2016      Published: February 04, 2016 ABSTRACT Wnt signaling pathway is aberrantly activated in a variety of cancers, especially in colorectal cancer and small molecule antagonists of Wnt/β-catenin signaling are attractive candidates for developing effective therapeutics. In the present study, we identified Bisleuconothine A, a bisindole alkaloid with an eburnane-aspidosperma type skeleton, as a novel and selective Wnt signaling inhibitor by using a cell-based luciferase assay system. Our study found that Bisleuconothine A down-regulated the endogenous Wnt target gene expression through promoting phosphorylation of β-catenin and the subsequent inhibition of its nuclear translocation in HCT116 and SW480 colorectal cancer cells. In vitro , Bisleuconothine A inhibited cell proliferation through induction of apoptosis by increasing the cleavage of caspases in HCT116 and SW480 colorectal cancer cells. Moreover, in vivo , Bisleuconothine A dramatically suppressed tumor growth in HCT116 Xenograft. And further analysis showed that Bisleuconothine A suppressed the Wnt target gene expression in HCT116 Xenograft, which was associated with up-regulation of β-catenin phosphorylation and subsequent Wnt signaling inhibition. Taken together, our study indicated that bisindole alkaloids could be included as a new chemotype of small-molecule Wnt signaling inhibitors, and have great potential to be further developed for anti-tumor agents." @default.
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• W2253992326 date "2016-02-04" @default.
• W2253992326 modified "2023-10-18" @default.
• W2253992326 title "Bisleuconothine A, a bisindole alkaloid, inhibits colorectal cancer cell <i>in vitro</i> and <i>in vivo</i> targeting Wnt signaling" @default.
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• W2253992326 doi "https://doi.org/10.18632/oncotarget.7190" @default.
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