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Updated: Dec 13, 2025
In vitro Organoid Culture of Primary Mouse Colon Tumors
Published on: May 17, 2013
Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling
Takahiro Hamoya1,2,3, Gen Fujii4, Yosuke Iizumi1
1Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
Abstract:
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.
Insights
Artesunate, an antimalarial, was found to prevent colorectal cancer by inhibiting intestinal polyp growth. It works by blocking the TCF/LEF pathway, offering a new approach for cancer chemoprevention.
Area of Science:
- Oncology
- Pharmacology
Background:
- Artesunate (ART) is an approved antimalarial drug.
- ART has shown potential as a colorectal cancer chemopreventive agent.
Purpose of the Study:
- To investigate the suppressive effects of ART on intestinal tumorigenesis.
- To elucidate the mechanism by which ART inhibits colorectal cancer development.
Main Methods:
- In vitro assays to assess T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity.
- In vivo studies to evaluate ART's effect on intestinal polyp development.
- Analysis of ART's interaction with Ras-related nuclear protein (RAN) and TCF1/TCF7 nuclear translocation.
Main Results:
- ART reduced TCF/LEF promoter transcriptional activity in vitro.
- ART significantly inhibited intestinal polyp formation in vivo.
- ART was found to bind to RAN, inhibiting TCF1/TCF7 nuclear translocation and Wnt signaling.
Conclusions:
- Artesunate effectively suppresses intestinal tumorigenesis.
- ART inhibits colorectal cancer by blocking the Wnt signaling pathway via RAN-mediated inhibition of TCF/LEF nuclear translocation.
- ART represents a novel therapeutic strategy for colorectal cancer chemoprevention.
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