Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling

Takahiro Hamoya, Gen Fujii, Yosuke Iizumi, Takumi Narita, Masami Komiya, Yui Matsuzawa, Kohei Miki, Tadashi Kondo, Shinji Kishimoto, Kenji Watanabe, Keiji Wakabayashi, Toshiyuki Sakai, Jiro Toshima, Michihiro Mutoh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)148-158
Number of pages11
JournalCarcinogenesis
Volume42
Issue number1
DOIs
Publication statusPublished - 11 Feb 2021

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