Bisleuconothine A, a bisindole alkaloid, inhibits colorectal cancer cell in vitro and in vivo targeting Wnt signaling
Kong, Ling-Mei1,2; Feng, Tao1; Wang, Yuan-Yuan3; Li, Xing-Yao1,4; Ye, Zhen-Nan1,2; An, Tao1,2; Qing, Chen5; Luo, Xiao-Dong1; Li, Yan1
2016-03-01
Source PublicationONCOTARGET
Volume7Issue:9Pages:10203-10214
AbstractWnt signaling pathway is aberrantly activated in a variety of cancers, especially in colorectal cancer and small molecule antagonists of Wnt/beta-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 beta-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 beta-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.
KeywordBisleuconothine a Inhibitor Wnt Signaling Colorectal Cancer Cells
Indexed BySCI
Language英语
WOS IDWOS:000375672900045
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Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/26251
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Harbin Inst Technol Weihai, Weihai 264209, Peoples R China
4.Georgia Regents Univ Hlth Sci Campus, Augusta, GA 30912 USA
5.Kunming Med Univ, Kunming 650500, Peoples R China
Recommended Citation
GB/T 7714
Kong, Ling-Mei,Feng, Tao,Wang, Yuan-Yuan,et al. Bisleuconothine A, a bisindole alkaloid, inhibits colorectal cancer cell in vitro and in vivo targeting Wnt signaling[J]. ONCOTARGET,2016,7(9):10203-10214.
APA Kong, Ling-Mei.,Feng, Tao.,Wang, Yuan-Yuan.,Li, Xing-Yao.,Ye, Zhen-Nan.,...&Li, Yan.(2016).Bisleuconothine A, a bisindole alkaloid, inhibits colorectal cancer cell in vitro and in vivo targeting Wnt signaling.ONCOTARGET,7(9),10203-10214.
MLA Kong, Ling-Mei,et al."Bisleuconothine A, a bisindole alkaloid, inhibits colorectal cancer cell in vitro and in vivo targeting Wnt signaling".ONCOTARGET 7.9(2016):10203-10214.
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