Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling.

Affiliation

Hamoya T(1)(2)(3), Fujii G(4), Iizumi Y(1), Narita T(1)(2), Komiya M(2), Matsuzawa Y(2)(3), Miki K(2)(3), Kondo T(5), Kishimoto S(6), Watanabe K(6), Wakabayashi K(7), Sakai T(8), Toshima J(3), Mutoh M(1)(2)(3)(9).
Author information:
(1)Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
(2)Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tsukiji, Chuo-ku, Tokyo, Japan.
(3)Department of Biological Science and Technology, Tokyo University of Science, Niijuku, Katsushika-ku, Tokyo, Japan.
(4)Central Radioisotope Division, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
(5)Division of Rare Cancer Research, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
(6)Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
(7)Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
(8)Department of Drug Discovery Medicine, Drug Discovery Center, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.
(9)Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, 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.