2005 Fiscal Year Final Research Report Summary
HUMULONE, A POTENT COX-2 INHIBITOR FROM BEER HOP, INHIBITS ANGIOGENESIS
| Project/Area Number |
16590445
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE |
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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)
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| 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)
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| Project Period (FY) |
2004 – 2005
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| Keywords | HUMULONE / ANGIOGENESIS / CYCLOOXYGENASE-2 / ANGIOGENESIS INHIBITION / CAM / ENDOTHELIAL CELLS / TRANSCRIPTION INHIBITOR / METASTASIS |
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| 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.
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Research Products
(17 results)
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[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.
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Journal Title
Carcinogenesis & Modification of Carcinogenesis
Pages: 229-242
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Pain Research 20
Pages: 27-34
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
J.Electrophoresis 49
Pages: 23-27
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Int.J.Cancer 111
Pages: 111-116
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[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.
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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
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[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.
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Journal Title
Milk Science 53
Pages: 273-274
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Milk Science 53
Pages: 225-229
Description
「研究成果報告書概要(欧文)」より
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