1. Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling.
- Author
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Hamoya, Takahiro, Fujii, Gen, Iizumi, Yosuke, Narita, Takumi, Komiya, Masami, Matsuzawa, Yui, Miki, Kohei, Kondo, Tadashi, Kishimoto, Shinji, Watanabe, Kenji, Wakabayashi, Keiji, Sakai, Toshiyuki, Toshima, Jiro, and Mutoh, Michihiro
- Subjects
WNT signal transduction ,NEOPLASTIC cell transformation ,INTESTINAL polyps ,NUCLEAR proteins - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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