Functional analysis of novel PPAR agonist on the growth of pancreatic cancer cells.

• Project/Area Number: 19591090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: SATO Mayumi Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 主任研究員 (50124459)
• Co-Investigator(Renkei-kenkyūsha): OIKAWA Tutomu 神奈川県立保健福祉大学, 保健福祉学部, 教授 (40120141)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 核内受容体 / PPAR / 膵がん / 細胞周期 / RXR / ANGPTL4 / 網羅的解析 / RNAi / PPARリガンド / 膵臓癌 / RXRリガンド / マイクロアレイ / 脂肪細胞

Research Abstract

受容体型転写因子PPARのアゴニストは19種のがん細胞の増殖を抑制するが、その機構は不明である。この受容体のアゴニストである新規創成化合物TIPP703を用いて、PPARγ応答領域を介して増殖抑制に関与する標的分子を探索した。TIPP703は膵がん細胞の90%をG0G1期 (DNA合成準備期)に留めることでDNA合成を阻害し細胞の増殖を抑制した。さらにマイクロアレイ法とRNAi 法を用いて、TIPP703 が ANGPTL4の発現を誘導し、すい癌の増殖を抑制するという新事実を見いだした。

Research Products

• [Journal Article] Identification of nobiletin, a polymethoxy flavonoid, as an enhancer of adiponectin secretion. Bioorg. (2009)
  • Author(s): Kunimasa, K., Kuranuki, S., Matsuura, N., Ikeda, M., Ito, A., Sashida, Y., Mimaki, Y., Yano, M., Sato, M., Igarashi, Y., Oikawa, T.
  • Journal Title: Med. Chem. Lett. 19 Pages: 2062-2064
  • Peer Reviewed
• [Journal Article] Identification of nobiletin, a polymethoxyflavonoid, as an enhancer of adiponectin secretion (2009)
  • Author(s): Kunimasa, K., Kuranuki, S., Matsuura, N., Ikeda, M., Ito, A., Sashida, Y., Mimaki, Y., Yano, M., Sato. M.
  • Journal Title: Bioorg. Med. Chem. Lett. 19 Pages: 2062-2064
  • Peer Reviewed
• [Journal Article] SAR-oriented discovery of peroxisome proliferator-activated receptor pn agonist with a 4-adamantylphenyl group as a hydrophobic tail. (2008)
  • Author(s): Kasuga J, Yamasaki D, Ogura K, Shimizu M, Sato M, Makishima M, Doi T, Hashimoto Y, Miyachi H.
  • Journal Title: Bioorg Med Chem Lett. 18 Pages: 1110-1115
  • Peer Reviewed
• [Journal Article] 脂肪細胞の分化におけるカルパインの役割 (2008)
  • Author(s): 矢島由起子, 佐藤眞友美
  • Journal Title: 生体の科学 59 Pages: 181-188
  • Peer Reviewed
• [Journal Article] SAR-oriented discovery of peroxisome proliferator-activated receptor pan agonist with a 4-adamantylphenyl group as a hydrophobic tail. (2008)
  • Author(s): Kasuga J, Yamasaki D, Ogura K, Shimizu M, Sato M, Makishima M, Doi T, Hashimoto Y, Miyachi H
  • Journal Title: Bioorg Med Chem Lett 18 Pages: 1110-1115
  • Peer Reviewed
• [Journal Article] All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor : possible involvement of paracrine effects of endogenous vascular endothelial growth factor signaling (2007)
  • Author(s): Akiko Saito, Akira Sugawara, Akira Uruno, Masataka Kudo, Hiroyuki Kagechika, Yasufumi Sato, Yuji Owada, Hisatake Kondo, Mayumi Sato, Masahiko Kurabayashi, Masue Imaizumi, Shigeru Tsuchiya and Sadayoshi Ito.
  • Journal Title: Endocrinology 148 Pages: 1412-1423
  • Peer Reviewed
• [Journal Article] Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. (2007)
  • Author(s): Lee S, Shinji C, Ogura K, Shimizu M, Maeda S, Sato M, Yoshida M, Hashimoto Y, and Miyachi H.
  • Journal Title: Bioorg Med Chem Lett. 17 Pages: 4895-4900
  • Peer Reviewed
• [Journal Article] Kurakata.Dipalmitoylation of radicicol results in improved efficacy against tumor growth and angiogenesis in vivo. (2007)
  • Author(s): T. Oikawa, C. Onozawa, Kuranuki, Y. M. Sato, H. Ashino, M. Toi and S. Kurakata.
  • Journal Title: Cancer Science 98 Pages: 219-225
  • Peer Reviewed
• [Journal Article] Design,synthesis,and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase(HDAC)inhibitors. (2007)
  • Author(s): Lee S, Shinji C, Ogura K, Shimizu M, Maeda S, Sato M, Yoshida M, Hashimoto Y, Miyachi H.
  • Journal Title: Bioorg Med Chem Lett 17 Pages: 4895-4900
  • Peer Reviewed
• [Journal Article] All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor:possible involvement of paracrine effects of endogenousvascular endothelial growth factor signaling (2007)
  • Author(s): A Saito, A Sugawara, A Uruno, M Kudo, H Kagechika, Y Sato, Y Owada, H Kondo, M Sato, K Kurabayashi, M Imaizumi, S Tsuchiya, S Ito
  • Journal Title: Endocrinology 148 Pages: 1412-1423
  • Peer Reviewed
• [Presentation] 新規PPAR sリガンドによる膵がん細胞の細胞周期停止機構の解明 (2008)
  • Author(s): 佐藤眞友美, 矢島由起子, 小倉潔, 西藤泰昌, 宮地弘幸
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 2008-05-16
• [Presentation] 新規PPARsリガンドによる膵がん細胞の細胞周期停止機構の解明 (2008)
  • Author(s): 佐藤眞友美, 矢島由起子, 小倉潔, 西藤泰昌, 宮地弘幸
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
• [Presentation] 糸状菌が産生する dechloro- griseofulvin によるアディポネクチン発現促進作用 (2008)
  • Author(s): 浪川愛子, 倉貫早智, 佐藤眞友美, 安住美亜, 五十嵐康弘, 及川勉
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
• [Presentation] Design, stereo-controlled synthesis and evaluation of optically active substituted phenylpropanoic acid-based peroxisome-proliferator-activated receptor (PPAR) pan agonists. (2008)
  • Author(s): Miyachi, H., Kasuga, J., Ohyama, T., Sato, M., Mokishima, M., Doi, T., Morikawa, K., Hashimoto, Y.
  • Organizer: Symposium on Molecular Chirality
  • Place of Presentation: Okayama
• [Presentation] TIPP-703, A peroxisome proliferator-activated receptor pan agonist, induces a g1-phase arrest in human pancreatic carcinoma cell lines. 33rd FEBS Congres (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu, M., Miyachi H.
  • Organizer: 11th IUBMB Conference "Biochemistry of Cell Regulation"
  • Place of Presentation: Greece
• [Presentation] Effects of Hgs on metastasis ability of mouse melanoma B16 cells. (2008)
  • Author(s): Ogura, K., Kawashima, I., Sato, M., Shimizu, M.
  • Organizer: The 33rd FEBS Congress & 11th IUBMB Conference
  • Place of Presentation: Athens (Greece)
• [Presentation] SAR-oriented discovery of substituted phenyl propan-oic acid-based PPAR pan agonists as candidate antipancreatic cancer agents. (2008)
  • Author(s): Miyachi H., Kasuga, K., Sato, M., Makishima M., Doi, T., Morikawa, K., Hashimot, Y.
  • Organizer: International Symposium CBI
  • Place of Presentation: Tokyo
• [Presentation] A novel PPAR alpha/beta/gamma-pan agonist inhibits cell growth in human pancreatic cancer cell lines. (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu, M., nishitho, Y., Miyachi H.
  • Organizer: 67th Annual Meeting of the Japanese cancer association.
  • Place of Presentation: Nagoya
• [Presentation] Comprehensive gene expression analysis of melanoma B16 cells that Hgs expression level changed metastasis activity. (2008)
  • Author(s): Ogura, K., Kawashima, I., Ishikawa, Y-I., Sato, M., Shimizu, M.
  • Organizer: The 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] Analysis of antitumor activity of IL-2. (2008)
  • Author(s): Shimizu, M., Sato, M., Ogura, K., Nishito, Y., Takeda, Y., Mizuguchi, J, Yoshimoto, T.
  • Organizer: The 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] TIPP-703, A peroxisome proliferator-activated receptor pan agonist, induces a g1-phase arrest in human pancreatic carcinoma cell lines (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu, M., Miyachi H
  • Organizer: 33rd FEBS Congress-11th IUBMB Conference
  • Place of Presentation: Greece
• [Presentation] SAR-oriented discovery of substituted phenyl propanoic acid-based peroxisome proliferator-activated receptor (PPAR) pan agonists as candidate antipancreatic cancer agents (2008)
  • Author(s): Miyachi H., Kasuga, K., Sato, M., Makishima M., Doi, T., Morikawa, K., Hashimot, Y.
  • Organizer: International Symposium CBI 2008
  • Place of Presentation: Tokyo
• [Presentation] A novel PPAR alpha/beta/gamma-pan agonist inhibits cell growth in human pancreatic cancer cell lines (2008)
  • Author(s): Sato, M., Yajima Y., Ogura, K., Shimizu, M., nishitho, Y., Miyachi H
  • Organizer: 67th Annual Meeting of the Japanese cancer association
  • Place of Presentation: Nagoya
• [Presentation] A novel PPAR alpha/beta/gamma-pan agonist inhibits cell growth in human pancreatic cancer cell lines (2007)
  • Author(s): Sato, M., Yjima Y, Ogura K., Shimizu, M. Nishito Y., Miyachi H.
  • Organizer: The 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] PPAR αγデュアルリガンドによる膵がん細胞の細胞周期調節作用 (2007)
  • Author(s): 佐藤眞友美, 小倉潔, 矢島由起子, 国政和宏, 太田敏郎, 宮地弘幸
  • Organizer: 第80回日本内分泌学術集会
  • Place of Presentation: 東京
• [Presentation] Novel PPAR α,γ dual agonists induce a G1-phase arrest in pancreatic cancer cells. (2007)
  • Author(s): Sato, M., Ogura, K., Shimizu, M., Kunimasa, K., Ohta, T., Kaji, K., Miyachi., H.
  • Organizer: The 66^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] Effects of RNA interference of GEF-1/Hgs on metastasis of mouse melanoma B16 cells. (2007)
  • Author(s): Ogura, K., Horiguchi, S., Sato, M., Shimizu, M.
  • Organizer: The 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] Role of macrophages and neutrophils in antitumor activity of Fas ligand (CD95L)-expressing tumor. (2007)
  • Author(s): Shimizu, M., Sato, M., Ogura, K., Takeda, Y., Mizuguchi, J, Yoshimoto, T.
  • Organizer: The 66th Annual Meeting of the Japanese CancerAssociation
  • Place of Presentation: Yokohama
• [Presentation] 構造活性相関に基づいたPPARパンアゴニストのピンポイント創製とその抗膵がん活性 (2007)
  • Author(s): 宮地弘幸, 春日淳一, 佐藤眞友美, 槇島誠, 土井健史, 橋本祐一
  • Organizer: 第26回メディシナルケミストリーシンポジウム
  • Place of Presentation: 相模原
• [Presentation] PPARαγデュアルリガンドによる膵がん細胞の細胞周期調節作用 (2007)
  • Author(s): 佐藤 真友美, 矢島 由起子, 小倉 潔, 西藤 泰昌, 宮地 弘幸
  • Organizer: 第80回日本内分泌学会学術総会
  • Place of Presentation: 東京
• [Remarks]
  • URL: http://www.rinshoken.or.jp/
• [Remarks]
  • URL: http://www.rinshoken.or.jp/
• [Remarks]
  • URL: http://www.rinshoken.or.jp/database/database.htm