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
收藏
页数：8
相关论文
共 42 条
[1]   WNT signalling pathways as therapeutic targets in cancer [J].
Anastas, Jamie N. ;
Moon, Randall T. .
NATURE REVIEWS CANCER, 2013, 13 (01) :11-26
[2]   Organometallic compounds with biological activity: A very selective and highly potent cellular inhibitor for glycogen synthase kinase 3 [J].
Atilla-Gokcumen, G. Ekin ;
Williams, Douglas S. ;
Bregman, Howard ;
Pagano, Nicholas ;
Meggers, Eric .
CHEMBIOCHEM, 2006, 7 (09) :1443-1450
[3]   Triptolide sensitizes pancreatic cancer cells to TRAIL-induced activation of the Death Receptor pathway [J].
Chen, Zhiyu ;
Sangwan, Veena ;
Banerjee, Sulagna ;
Chugh, Rohit ;
Dudeja, Vikas ;
Vickers, Selwyn M. ;
Saluja, Ashok K. .
CANCER LETTERS, 2014, 348 (1-2) :156-166
[4]   Wnt/β-catenin signaling in development and disease [J].
Clevers, Hans .
CELL, 2006, 127 (03) :469-480
[5]   Triptolide Directly Inhibits dCTP Pyrophosphatase [J].
Corson, Timothy W. ;
Cavga, Hueseyin ;
Aberle, Nicholas ;
Crews, Craig M. .
CHEMBIOCHEM, 2011, 12 (11) :1767-1773
[6]   Canonical Wnt signalling as a key regulator of fibrogenesis - implications for targeted therapies? [J].
Dees, Clara ;
Distler, Joerg H. W. .
EXPERIMENTAL DERMATOLOGY, 2013, 22 (11) :710-713
[7]   Crystal structure of a β-catenin/Tcf complex [J].
Graham, TA ;
Weaver, C ;
Mao, F ;
Kimelman, D ;
Xu, WQ .
CELL, 2000, 103 (06) :885-896
[8]   Selective Small Molecule Targeting β-Catenin Function Discovered by In Vivo Chemical Genetic Screen [J].
Hao, Jijun ;
Ao, Ada ;
Zhou, Li ;
Murphy, Clare K. ;
Frist, Audrey Y. ;
Keel, Jessica J. ;
Thorne, Curtis A. ;
Kim, Kwangho ;
Lee, Ethan ;
Hong, Charles C. .
CELL REPORTS, 2013, 4 (05) :898-904
[9]   Modulation of IL-37 expression by triptolide and triptonide in THP-1 cells [J].
He, Lingge ;
Liang, Zhuangyan ;
Zhao, Fuqian ;
Peng, Lifei ;
Chen, Zhangquan .
CELLULAR & MOLECULAR IMMUNOLOGY, 2015, 12 (04) :515-518
[10]   A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon [J].
Heisenberg, CP ;
Houart, C ;
Take-uchi, M ;
Rauch, GJ ;
Young, N ;
Coutinho, P ;
Masai, I ;
Caneparo, L ;
Concha, ML ;
Geisler, R ;
Dale, TC ;
Wilson, SW ;
Stemple, DL .
GENES & DEVELOPMENT, 2001, 15 (11) :1427-1434
12345