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HUMULONE, A POTENT COX-2 INHIBITOR FROM BEER HOP, INHIBITS ANGIOGENESIS

Research Project

Project/Area Number 16590445
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionTHE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE

Principal Investigator

SHIMAMURA Mariko  THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, RESEARCHER, 東京都臨床医学総合研究所, 主任研究員 (00124462)

Co-Investigator(Kenkyū-buntansha) TOBE Hiroyasu  KOCHI NATIONAL COLLEGE OF TECHNOLOGY, DEPARTMENT OF MATERIALS SCIENCE AND TECHNOLOGY, PROFESSOR, 物質工学科, 教授 (30300643)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsHUMULONE / ANGIOGENESIS / CYCLOOXYGENASE-2 / ANGIOGENESIS INHIBITION / CAM / ENDOTHELIAL CELLS / TRANSCRIPTION INHIBITOR / METASTASIS / cyclooxygenase 2 / 鶏卵漿尿膜 / 抗腫瘍作用 / 腫瘍細胞 / cycloxygenase2 / dorsal air sac
Research Abstract

Angiogenesis, the formation of new capillary blood vessels for supplying oxygen and nutrients, is essential for their continuous growth and metastasis of solid tumors. The inhibition of tumor angiogenesis by potent angiogenic inhibitors may be a useful approach for cancer therapy. Recently, cyclooxygenase (COX), particularly COX-2, was postulated to be involved in tumor growth, metastasis and angiogenesis. To find a new potent angiogenic inhibitor, we focused our previous finding that humulone, a bitter acid from beer hop (Humulus lupulus L.) was a potent inhibitor of bone resorption and inhibited catalytic activity of cyclooxygenase-2 and more potently the transcription of COX-2 gene.
We first examined the effect of humulone on angiogenesis, using chick embryo chorioallantoic membranes (CAM) and vascular endothelial and tumor cells. Humulone significantly prevented in vivo angiogenesis in CAM in a dose dependent manner. Humulone potently inhibited the proliferation of endothelial cells stimulated by bFGF, VEGF and serum. It also suppressed in vitro angiogenesis of vascular endothelial tube formation and production of angiogenic factor (VEGF) in endothelial and tumor cells. We next examined the effects of the synthesized or purified compounds derived from humulone on angiogenesis in CAM. Among the compounds tested, humulone was the most potent angiogenesis inhibitor. Therefore, we synthesized large volume of humulone and examined in vivo assays in mice. Humulone inhibited tumor-induced angiogenesis in mouse dorsal air sac assay and also suppressed spontaneous lung metastasis of tumor cells by intraperitoneal administration. On the bases of these results, humulone is a potent angiogenesis inhibitor, and may be a novel powerful tool for the therapy in various angiogenic diseases involving solid tumor, rheumatoid arthritis and diabetic retinopathy.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (29 results)

All 2005 2004

All Journal Article (27 results) Book (2 results)

  • [Journal Article] Cancer prevention and anti-metastatic effect by oral administration of bovine lactoferrin.2005

    • Author(s)
      Shimamura, M., et al.
    • Journal Title

      Carcinogenesis and Modification of Carcinogenesis 1

      Pages: 229-242

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Levels of spinorphin in carebrospinal fluid derived from patients with pain increase with decreasing dipeptidyl peptidase III.2005

    • Author(s)
      Shimamura, M., et al.
    • Journal Title

      Pain Research 20

      Pages: 27-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cancer prevention and anti-metastatic effect by oral administration of bovine lactoferrin.2005

    • Author(s)
      Iigo, M., Shimamura, M., Hirano, S., Nabeshima, K., Ohkubo, S., Tamura Y., Tsuda, H.
    • Journal Title

      Carcinogenesis & Modification of Carcinogenesis

      Pages: 229-242

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Levels of spinorphin in cerebrospinal fluid derived from patients with pain increase with decreasing dipeptidyl peptidase III.2005

    • Author(s)
      Yamamoto, Y., Sato, H., Fukasaku, S., Hiramatsu, K., Tai, S., Shimamura M., Hazato, T.
    • Journal Title

      Pain Research 20

      Pages: 27-34

    • NAID

      10015444541

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Two-dimensional electrophoretic analysis of disease-associated proteins in human cerebrospinal fluid from patients with rheumatoid arthritis.2005

    • Author(s)
      Yamamoto, Y., Akita, Y., Tai, S., Fukasaku, S., Yamaguchi, T., Oshizawa, T., Yamaoka, K., Shimamura, M., Hazato, T.
    • Journal Title

      J.Electrophoresis 49

      Pages: 23-27

    • NAID

      10015570338

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antitumor effect of a novel IL6/IL12 family cytokine IL-27.2005

    • Author(s)
      Yoshimoto, T., Hisada, M., Shimizu, M., Shimamura, M., Mizuguchi, J.
    • Journal Title

      Rinshomeneki 43

      Pages: 123-128

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Levels of spinorphin in cerebrospinal fluid derived from patients with pain increase with decreasing dipeptidyl peptidase III.2005

    • Author(s)
      Shimamura, M., et al.
    • Journal Title

      Pain Research 20

      Pages: 27-34

    • NAID

      10015444541

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Two-dimensional electrophoretic analysis of disease-associated proteins in human cerebrospinal fluid from patients with rheumatoid arthritis.2005

    • Author(s)
      Shimamura, M., et al.
    • Journal Title

      J.Electrophoresis 49

      Pages: 23-27

    • NAID

      10015570338

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ウシラクトフェリン免疫能増強および血管新生阻害作用による発がん抑制と臨床応用.2005

    • Author(s)
      島村眞里子, 他
    • Journal Title

      Milk Science 54

      Pages: 273-274

    • Related Report
      2005 Annual Research Report
  • [Journal Article] がん予防-多機能生理活性物質ラクトフェリンからメッセージ-.2005

    • Author(s)
      島村眞里子, 他
    • Journal Title

      Milk Science 53

      Pages: 225-229

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 新しいIL-6/IL-12ファミリーサイトカインIL-27の抗腫瘍効果2005

    • Author(s)
      島村眞里子, 他
    • Journal Title

      臨床免疫 43

      Pages: 123-128

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Levels of spinorphin in cerebrospinal fluid derived from patients with pain increase with decreasing dipeptidyl peptidase III2005

    • Author(s)
      Shimamura, N.et al.
    • Journal Title

      Pain Research (In press)

    • NAID

      10015444541

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Two-dimensional electrophoretic analysis of disease-associated proteins in human cerebrospinal fluid from patients with rheumatoid arthritis.2005

    • Author(s)
      Shimamura, N.et al.
    • Journal Title

      J.Electrophoresis (In press)

    • NAID

      10015570338

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Bovine lactoferrin inhibits tumor-induced angiogenesis.2004

    • Author(s)
      Shimamura, M., et al.
    • Journal Title

      Intl. J. Cancer 111

      Pages: 111-116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Orlly administered bovine lactoferrin induces caspase-1 and interleukin-18 in the mouse intestinal mucosa : A possible explanation for inhbition of carcinogenesis and metastasis.2004

    • Author(s)
      Shimamura, M., et al.
    • Journal Title

      Cytokines 25

      Pages: 36-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Angiogenesis inhibitor TX-1898 : syntheses of the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitroimidazole hypoxic cell radiosensitizers.2004

    • Author(s)
      Shimamura, M., et al.
    • Journal Title

      Bioorg. Med. Chem. 12

      Pages: 4917-4927

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Design of hypoxia targeting protein tyrosine kinase inhibitor using an innovative pharmacophore 2-methylene-4-cyclopentene-1,3-dione2004

    • Author(s)
      Shimamura, et al.
    • Journal Title

      Biochim. Biophys. Acta-protein and proteomics- 1697

      Pages: 29-38

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bovine lactoferrin inhibits tumor-induced angiogenesis.2004

    • Author(s)
      Shimamura, M., Yamamoto, Y., Ashino, H., Oikawa, T., Hazato, T., Tsuda, H., Iigo, M.
    • Journal Title

      Int.J.Cancer 111

      Pages: 111-116

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Orally administered bovine lactoferrin induces caspase-1 and interleukin-18 in the mouse intestinal mucosa : A possible explanation for inhibition of carcinogenesis and metastasis.2004

    • Author(s)
      Iigo, M., Shimamura, M., Matsuda, E., Fujita, K., Nomoto, H., Satoh, J., Kojima, K., Moore, M., Tsuda, H.
    • Journal Title

      Cytokine 25

      Pages: 36-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Angiogenesis inhibitor TX-1898 : syntheses of the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitro imidazole hypoxic cell radiosensitizers.2004

    • Author(s)
      Jin CZ, Nagasawa H, Shimamura M, Uto Y, Inayama S, Takeuchi Y, Kirk KL, Hori H.
    • Journal Title

      Bioorg Med Chem. 12

      Pages: 4917-4927

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Design of hypoxia targeting protein tyrosine kinase inhibitor using an innovative pharmacophore 2-methylene-4-cyclopentene-1,3-dione.2004

    • Author(s)
      Hori, H., Nagasawa, H., Uto, Y., Ohkura, K., Kirk, K.L, Uehara, Y., Shimamura, M.
    • Journal Title

      Biochim.Biophys.Acta -protein and proteomics-. 1697

      Pages: 29-38

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cancer prevention by lactoferrin is accompanied by inhibition of angiogenesis.2004

    • Author(s)
      Iigo, M., Shimamura, M., Nabeshima, K., Wakabayashi, H., Ohkubo, S., Tamura, Y., Tsuda, H.
    • Journal Title

      Milk Science 53

      Pages: 273-274

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cancer prevention -A message from multifunctional natural compounds-.2004

    • Author(s)
      Tsuda, H., Ohshima, H., Fukamachi, K., Iigo, M., Takasuka, N., Matsuda, E., Sekine, K., ohkubo, S., Kohzu, T., Shimamura, M.
    • Journal Title

      Milk Science 53

      Pages: 225-229

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bovine lactoferrin inhibits tomor-induced angiogenesis2004

    • Author(s)
      Shimamura, M.et al.
    • Journal Title

      Intl.J.Cancer 111

      Pages: 111-116

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Orally administered bovine lactoferrin induces caspase-1 and inter-leukin-18 in the mouse intestinal mucosa2004

    • Author(s)
      Shimamura, M.et al.
    • Journal Title

      Cytokine 25

      Pages: 36-44

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Angiogenesis inhibitor TX-1898: syntheses of the enantiomers of sterically diverse haloacetylcdarbamoyl-2-nitroimidazole hypoxic cell radiosensitizers2004

    • Author(s)
      Shimamura, M.et al.
    • Journal Title

      Bioorg Med Chem 12

      Pages: 4917-4927

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Design of hypoxia targeting protein tyrosine kinase inhibitor using an 2innovative pharmacophore 2-methylene-4-cyclopentene-1,3-dione2004

    • Author(s)
      Shimamura, M.et al.
    • Journal Title

      Biochim.Biophys.Acta -protein and proteomics- 1697

      Pages: 29-38

    • Related Report
      2004 Annual Research Report
  • [Book] がん予防食品開発の新展開・予防医学におけるバイオマーカーの評価システム2005

    • Author(s)
      島村眞里子他
    • Publisher
      ラクトフェリン・多機能性天然由来物質によるがん予防
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] がん予防食品開発の新展開 -予防医学におけるバイオマーカーの評価システム-2005

    • Author(s)
      島村眞里子, 他
    • Publisher
      シーエムシー出版
    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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