Resveratrol inhibits development of colorectal adenoma via suppression of LEF1; comprehensive analysis with connectivity map

• 資料種別: 博士論文
• タイトル: Resveratrol inhibits development of colorectal adenoma via suppression of LEF1; comprehensive analysis with connectivity map
• 著者・編者: Wada, Hironori; Sato, Yasushi; Fujimoto, Shota; Okamoto, Koichi; Bando, Masahiro; Kawaguchi, Tomoyuki; Miyamoto, Hiroshi; Muguruma, Naoki; Horimoto, Katsuhisa; Matsuzawa, Yui; Mutoh, Michihiro; Takayama, Tetsuji
• 著者標目: Wada, Hironori; Sato, Yasushi; Fujimoto, Shota; Okamoto, Koichi; Bando, Masahiro; Kawaguchi, Tomoyuki; Miyamoto, Hiroshi; Muguruma, Naoki; Horimoto, Katsuhisa; Matsuzawa, Yui; Mutoh, Michihiro; Takayama, Tetsuji
• 出版事項: Japanese Cancer Association|John Wiley & Sons
• 出版年月日等: 2022-09-09
• 出版年（W3CDTF）: 2022-09-09
• 並列タイトル等: ResveratrolはLEF1を抑制することで大腸腺腫の発生を抑制する；connectivity mapを用いた網羅的解析
• タイトル（掲載誌）: Cancer Science
• 巻号年月日等（掲載誌）: 113 12
• 掲載巻: 113
• 掲載号: 12
• 掲載ページ: 4374-4384
• ISSN（掲載誌）: ISSN : 1349-7006
• 授与機関名: 徳島大学
• 授与年月日: 2023-01-26
• 報告番号: 甲第3670号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: chemoprevention; colorectal adenoma; connectivity map; LEF1; resveratrol
• 対象利用者: 一般
• 一般注記: Although many chemopreventive studies on colorectal tumors have been reported, no effective and safe preventive agent is currently available. We searched for candidate preventive compounds against colorectal tumor comprehensively from United States Food and Drug Administration (FDA)-approved compounds by using connectivity map (CMAP) analysis coupled with in vitro screening with colorectal adenoma (CRA) patient-derived organoids (PDOs). We generated CRA-specific gene signatures based on the DNA microarray analysis of CRA and normal epithelial specimens, applied them to CMAP analysis with 1309 FDA-approved compounds, and identified 121 candidate compounds that should cancel the gene signatures. We narrowed them down to 15 compounds, and evaluated their inhibitory effects on the growth of CRA-PDOs in vitro. We finally identified resveratrol, one of the polyphenolic phytochemicals, as a compound showing the strongest inhibitory effect on the growth of CRA-PDOs compared with normal epithelial PDOs. When resveratrol was administered to ApcMin/+ mice at 15 or 30 mg/kg, the number of polyps (adenomas) was significantly reduced in both groups compared with control mice. Similarly, the number of polyps (adenomas) was significantly reduced in azoxymethane-injected rats treated with 10 or 100 mg/resveratrol compared with control rats. Microarray analysis of adenomas from resveratrol-treated rats revealed the highest change (downregulation) in expression of LEF1, a key molecule in the Wnt signaling pathway. Treatment with resveratrol significantly downregulated the Wnt-target gene (MYC) in CRA-PDOs. Our data demonstrated that resveratrol can be the most effective compound for chemoprevention of colorectal tumors, the efficacy of which is mediated through suppression of LEF1 expression in the Wnt signaling pathway.
• オンライン閲覧公開範囲: インターネット公開
• 著作権情報: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
• 関連情報（DOI）: 10.1111/cas.15576
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

http://repo.lib.tokushima-u.ac.jp/files/public/11/117988/20230410110634453802/k3670_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/117988/20230410110634740738/k3670_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/117988/2023041011063521182/k3670_fulltext.pdf fulltext