| Project/Area Number |
02042009
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Special Cancer Research |
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| Research Institution | National Cancer Center Research Institute |
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Principal Investigator |
FUJIKI Hirota Chief, Cancer Prevention Division, National Cancer Center Research Institute, がん予防研究部, 部長 (60124426)
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| Co-Investigator(Kenkyū-buntansha) |
R J.Quinn Director, Queensland Pharmaceutical Research Institute School of Science Griffit, 薬理学研究所, 所長
J T.Baker Director, Australian Institute of Marine Science, 所長
SUGANUMA Masami Researcher, Cancer Prevention Division, National Cancer Center Research Institut, がん予防研究部, 研究員 (20196695)
KAMIYA Hisao Professor, School of Fisheries Sciences Kitasato University, 水産学部, 教授 (80011964)
FUSETANI Nobuhiro Professor, Laboratory of Marine Biochemistry Faculty of Agriculture, The Univers, 水産化学研究室, 教授 (70012010)
QUINN R.J. グリフィス大学, 薬理学研究所, 所長
BAKER J.T. オーストリラア海洋化学研究所, 所長
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| Project Period (FY) |
1989 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 1992: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1991: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1990: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Antifungal agent / Anticancer agent / Echinoclasterol sulfate / Antioxidant / Mycosporine-glycine / Okadaic acid class tumor promoter / Molecular modeling / オ-ストラリア / 海洋天然物 / オカダ酸クラス発がんプロモ-タ- / プロテインフォスファタ-ゼ / タンパク質イソプレニ-ル化 / コンピュ-タ-分子モデリング / オカダ酸 / Dr.Baker / Dr.Quinn |
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| Research Abstract |
This research program from 1991 to 1993 provided three important pieces of evidence, as follows.
1. Discovery of a new antifungal and anticancer agent, Echinoclasterol sulfate.
From the Australian Institute of Marine Science, 25 marine organisms were mailed to Japan and their extracts were subjected to various assay systems. The water soluble fraction of the MeOH extract of the marine sponge, Echinoclathria subhispida, showed a strong antifungal activity against Mortierella remannianus. The active principle was isolated and characterized as the first phenathylammonium salt of a novel polyoxygenated sterol sulfate, named "Echinoclasterol sulfate". Echinoclasterol sulfate also showed an inhibitory effect on cell growth of PC-9, a lung cancer cell line, dose-dependently. The IC_<50> value was 600 muM. Its anticancer activity is about 300 times weaker than adriamycin.
2. Isolation of a new antioxidant.
An edible algae, Nori Porphyra tenera, contains shinorine, which does not have any antioxidant activity itself. However, the enzyme fraction obtained from a marine organism converted shinorine to a new antioxidant, mycosporine-glycine. A method of large scale preparation of mycosporine-glycine is now under investigation.
3. Computer assisted molecular modeling of the okadaic acid class compounds.
Three okadaic acid class compounds, okadaic acid, calyculin A, and microcystin-LR, are potent inhibitors of protein phosphatases 1 and 2A. Although their structures are not related to each other, they were assumed to bind to same site of a catalytic subunit of the protein phosphatases. Computer assisted molecular modeling revealed that three okadaic acid class compounds have common structural features, such as the central core of the molecules, for the inhibitory activity and non-polar side chains for binding activity.
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