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- Title
Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling.
- Authors
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; Mutoh, Michihiro
- 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.
- Subjects
WNT signal transduction; NEOPLASTIC cell transformation; INTESTINAL polyps; NUCLEAR proteins
- Publication
Carcinogenesis, 2021, Vol 42, Issue 1, p148
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgaa084