Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling-Reference-Cited by-同舟云学术

Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling

Published:2020-07-25 Issue:1 Volume:42 Page:148-158
ISSN:0143-3334
Container-title:Carcinogenesis
language:en
Short-container-title:

Author:

Hamoya Takahiro¹²³,Fujii Gen⁴,Iizumi Yosuke¹,Narita Takumi¹²,Komiya Masami²,Matsuzawa Yui²³,Miki Kohei²³,Kondo Tadashi⁵,Kishimoto Shinji⁶,Watanabe Kenji⁶,Wakabayashi Keiji⁷,Sakai Toshiyuki⁸,Toshima Jiro³,Mutoh Michihiro¹²³⁹

Affiliation:

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

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.

Funder

Japan Agency for Medical Research and Development

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

Link

http://academic.oup.com/carcin/advance-article-pdf/doi/10.1093/carcin/bgaa084/33652804/bgaa084.pdf

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