Triptonide Effectively Inhibits Wnt/β-Catenin Signaling via C-terminal Transactivation Domain of β-catenin

被引：35

作者：

Chinison, Jessica ^{[1
]}

Aguilar, Jose S. ^{[1
]}

Avalos, Alan ^{[1
]}

Huang, Ying ^{[2
]}

Wang, Zhijun ^{[2
]}

Cameron, D. Joshua ^{[3
]}

Hao, Jijun ^{[1
,4
]}

机构：

[1] Western Univ Hlth Sci, Coll Vet Med, Pomona, CA 91766 USA

[2] Western Univ Hlth Sci, Coll Pharm, Pomona, CA 91766 USA

[3] Western Univ Hlth Sci, Coll Optometry, Pomona, CA 91766 USA

[4] Western Univ Hlth Sci, Grad Coll Biomed Sci, Pomona, CA 91766 USA

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

CANCER CELLS; CRYSTAL-STRUCTURE; TRIPTOLIDE; ZEBRAFISH; MODULATION; ACTIVATION; ARMADILLO; PRODUCT; COMPLEX; DEATH;

D O I：

10.1038/srep32779

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Abnormal activation of canonical Wnt/beta-catenin signaling is implicated in many diseases including cancer. As a result, therapeutic agents that disrupt this signaling pathway have been highly sought after. Triptonide is a key bioactive small molecule identified in a traditional Chinese medicine named Tripterygium wilfordii Hook F., and it has a broad spectrum of biological functions. Here we show that triptonide can effectively inhibit canonical Wnt/beta-catenin signaling by targeting the downstream C-terminal transcription domain of beta-catenin or a nuclear component associated with beta-catenin. In addition, triptonide treatment robustly rescued the zebrafish "eyeless" phenotype induced by GSK-3 beta antagonist 6-bromoindirubin-30-oxime (BIO) for Wnt signaling activation during embryonic gastrulation. Finally, triptonide effectively induced apoptosis of Wnt-dependent cancer cells, supporting the therapeutic potential of triptonide.

引用

页数：8

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