Journal
CARCINOGENESIS
Volume 42, Issue 1, Pages 148-158Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgaa084
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Funding
- Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development [19ck0106271h0003]
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Artesunate inhibits intestinal tumorigenesis by reducing the nuclear translocation of TCF/LEF transcription factors, thereby suppressing Wnt signaling.
Artesunate (ART) is a clinically approved antimalarial drug and was revealed as a candidate of colorectal cancer chemopreventive agents in our drug screening system. Here, we aimed to understand the suppressive effects of ART on intestinal tumorigenesis. In vitro, ART reduced T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter transcriptional activity. In vivo, ART inhibited intestinal polyp development. We found that ART reduces TCF1/TCF7 nuclear translocation by binding the Ras-related nuclear protein (RAN), suggesting that ART inhibits TCF/LEF transcriptional factor nuclear translocation by binding to RAN, thereby inhibiting Wnt signaling. Our results provide a novel mechanism through which artesunate inhibits intestinal tumorigenesis.
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