| Co-Investigator(Kenkyū-buntansha) |
VRIES D.de オーストラリア海洋科学研究所, 主任研究員
MURPHY Peter Chief, Australian Institute of Marine Science, 部長
QUINN R.J. グリフィス大学薬理学研究所, 所長
SUGANUMA Masami Researcher, Saitama Cancer Center Res.Inst., 血清ウィルス部, 研究員 (20196695)
FUSETANI Nobuhiro Professor, Laboratory of Marine Biochemistry Faculty of Agriculture, The Univers, 水産科学研究所, 教授 (70012010)
DE VRIES David Researcher, Australian Institute of Marine Science
QUINN Ronald j. Director, Queensland Pharmaceutical Res.Inst.School of Science, Griffith Univers
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| Research Abstract |
1.Research puropose
In collaboration with Dr.Joe Baker, Australian Institute of Marine Science and Dr.Ronald Quinn, Griffith University, we studied mechanisms of carcinogenesis and inhibition of carcinogenesis using Australian marine natural products for the past three years. Based on these successful collaborations, we have investigated several new projects this time, for example, screening for cancer chemopreventive agents. In addition, we have been studying a general model of the okadaic acid class tumor promoters using a computer analysis.
2.Results
Several important results are summarized.
1) AIMS's group purified potent anti-oxidants from marine organisms and synthesized more stable analogs for using sunscreen. We studied the inhibitory effect of the sunscreen compound on tumor promotion by okadaic acid in mouse skin initiated with DMBA.The pretreatment of sunscreen compound enhanced tumor formation by okadaic acid. These results indicate complexity of carcinogenesis process.
2) We studied protein phosphatase 2A (PP2A) activity of 24 fractions of Australian marine organisms. One fraction isolated from marine sponge showed stimulation of protein phosphatase 2A.Agelasine-B was isolated as a active principle from the marine sponge, Agelas axifera. The effect of agelasine-B was contrary to that of okadaic acid, suggesting that agelasine-B has an inhibitory effect on okadaic acid.
3) The computer-assisted molecular modeling revealed that three okadaic acid class tumor promoters have a catalytic part and a receptor binding part in common. Based on the results, we started to synthesized chimeric compounds of microcystin and okadaic acid. Dr.Quinn's group synthesized precausors of microcystins without Adda. A cyclic peptide, M8, inhibited PP2A activity at 1 mM concentration. We will try to attach the spiroketal moiety of okadaic acid to M8. We expect that these results with the chimeric compound will confirm our computer generated molecular model.
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