Triptonide Effectively Inhibits Wnt/β-Catenin Signaling via C-terminal Transactivation Domain of β-catenin.
Abnormal activation of canonical Wnt/β-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/β-catenin signaling by targeting the downstream C-terminal transcription domain of β-catenin or a nuclear component associated with β-catenin. In addition, triptonide treatment robustly rescued the zebrafish "eyeless" phenotype induced by GSK-3β 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.
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
Jessica
J
Chinison
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
Jose S
JS
Aguilar
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
Alan
A
Avalos
College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
Ying
Y
Huang
College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
Zhijun
Z
Wang
College of Optometry, Western University of Health Sciences, Pomona, CA 91766, USA.
D Joshua
DJ
Cameron
College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.|Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA.
Jijun
J
Hao
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects*; D015533:Transcriptional Activation; D014315:Triterpenes / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish; D051176:beta Catenin / Q000378:metabolism*
C495270:CTNNB1 protein, human; D014315:Triterpenes; D051153:Wnt Proteins; D051176:beta Catenin; C084079:triptonide