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Studies on inhibitors of protein phosphatases and of protein isoprenylation, derived from Australian marine organisms

Research Project

Project/Area Number 05042010
Research Category

Grant-in-Aid for Overseas Scientific Survey.

Allocation TypeSingle-year Grants
SectionSpecial Cancer Research
Research InstitutionSaitama Cancer Center

Principal Investigator

FUJIKI Hirota  Vice director, Saitama Cancer Center Research Institute, 副所長 (60124426)

Co-Investigator(Kenkyū-buntansha) MURPHY P.  Chief, Australian Institute of Marine Science, 部長
QUINN R.J.  Director, Queensland Pharmaceutical Research Institute School of Science, Griffi, 薬理学研究所, 所長
BAKER J.  Director, Australian Institute of Marine Science, 所長
SUGANUMA Masami  Researcher, Saitama Cancer Center Research Institute, 血清ウィルス部, 研究員 (20196695)
FUSETANI Nobuhiro  Professor, Laboratory of Marine Biochemistry Faculty of Agriculture, The Univers, 教授 (70012010)
Project Period (FY) 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1993: ¥3,200,000 (Direct Cost: ¥3,200,000)
KeywordsMarine natural products / Protein phosphatase / protein isoprenylation / okadaic acid / anti-oxidant / Australia / anti-cancer agents / Computer graphics
Research Abstract

1. Research purpose
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 instigated several new projects this time, for example, screening for okadaic acid class tumor promoters, anti-okadaic acid class compound, the antioxidants and inhibitors of protein isoprenylation. 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. We studied protein phosphatase 2A activity of 24 fractions of Australian marine organisms. One fraction isolated from marine sponge showed stimulation of protein phosphatase 2A. The extract at a concentration of 1 mg/ml enhanced the PP2A activity 4 times. The effect was contrary to that of okadaic acid, suggesting that the extract has inhibitory effect on a tumor promoter, okadaic acid. We are now isolating active principles from the extract.
2. 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 synthesize chimeric compounds of calyculin A and microcystin-LR. Dr.Quinn's group synthesized a chimeric compound consisting of a receptor binding part of calyculin A and a catalytic part of microcystin-LR. We are now trying to measure its activity and compare it to those of the natural compounds, calyculin A and microcystin-LR. We expect that these results will confirm our computer generated molecular model.

Report

(1 results)
  • 1993 Final Research Report Summary
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] J.Yatsunami,H.Fujiki,et al.: "Hyperphosphorylation of retino-blastoma protein and p53 by okadaic acid,a tumor promoter" Cancer Res.53. 239-241 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Suganuma,H.Fujiki,et al.: "Absence of synergistic effects on tumor promotion in CD-1 mouse skin by simultaneous applications of two different types of tumor promoters,okadaic acid and teleocidin" Cancer Res.53. 1012-1016 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] J.Yatsunami,H.Fujiki,et al.: "Hyperphosphorylation of cytokeratins by okadaic acid class tumor promoters in primary human keratinocytes" Cancer Res.53. 992-996 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] C.A.Afshari,H.Fujiki,et al.: "Induction of neoplastic progression in syrian hamster embryo cells treated with protein phosphatase inhibitors" Cancer Res.53. 1777-1782 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] A.Komori,H.Fujiki,et al.: "Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation" Cancer Res.53. 1982-1985 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] H.Fujiki,M.Suganuma: "Tumor promotion by inhibitors of protein phosphatases 1 and 2A,the okadaic acid class of compounds" Adv.Cancer Res.61. 143-194 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] R.J.Quinn,H.Fujiki,et al.: "The conserved acid binding domain model of inhibitors of protein phosphatases 1 and 2A:Molecular modeling aspects" BioMed.Chem.Lett.6. 1029-1034 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] H.Y.Li,H.Fujiki,et al.: "Echinoclasterol sulfate phenetylammonium salt,a unique steroid sulfate from the marine sponge,echinoclathrea subhispida additional inhibitors of protein phosphatases 1 and 2A,from the marine sponge Discondermia Calyx" Tetrahedron Lett.34. 5733-5736 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Kanazawa,N.Fusetani,et al.: "Cylindramide:cytotoxic,tetramic acid lactam from the marine sponge Halichondria cylindrata Tanita & Hoshino" Tetrahedron Lett.34. 1065-1068 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Fusetani: "Antifungal brominated C18 acetylenic acids from the marine sponge,Petrosia volcano Hoshino" Tetrahedron Lett.49. 1203-1210 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Nakao,N.Fusetani,et al.: "Toxadocial A:novel thrombin inhibitor from the marine sponge Toxadocia cylindrica" Tetrahedron Lett.34. 1511 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Fusetani: "Cinachyrolide A:a potent cytotoxic macrolide possessing two spiro ketals from marine sponge Cinachyra sp." J.Am.Chem.Soc.115. 3977-3981 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] H.Yagi,N.Fusetani,et al.: "Purpuramines A-I,new bromotyrosine-derived metabolites from the marine sponge Psammaplysilla prupurea" Tetrahedron. 49. 3749-3754 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Fusetani: "Isolation and structure elucidation of erylusamine B,a new class of marine natural products,which blocked an IL-6 receptor,from the marine sponge Erylus placenta Thiele" Tetrahedron Lett.34. 4067-4070 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Fusetani: "Bioactive sponge peptides" Chem.Rev.93. 1793-1806 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Matsunaga,N.Fusetani,et al.: "Cribrochalinamine oxides A and B,antifungal β-substituted pyridines with an azomethine N-oxide from a marine sponge Cribrochalina sp." Tetrahedron Lett.34. 5953-5954 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] H.Fujiki,T.Ohta,et al.: "Significant marine natural products in cancer research" Gazzetta Chimica Italiana, 309-316 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] J.Yatsunami, H.Fujiki, et al.: "Hyperphosphorylation of retino-blastoma protein and p53 by okadaic acid, a tumor promoter" Cancer Res.53. 239-241 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Suganuma, H.Fujiki, et al.: "Absence of synergistic effects on tumor promotion in CD-1 mouse skin by simultaneous applications of two different types of tumor promoters, okadaic acid and teleocidin" Cancer Res.53. 1012-1016 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] J.Yatsunami, H.Fujiki, et al.: "Hyperphosphorylation of cytokeratins by okadaic acid class tumor promoters in primary human keratinocytes" Cancer Res.53. 992-996 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] C.A.Afshari, H.Fujiki, et al.: "Induction of neoplastic progression in syrian hamster embryo cells treated with protein phosphatase inhibitors" Cancer Res.53. 1777-1782 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] A.Komori, H.Fujiki, et al.: "Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation" Cancer Res.53. 1982-1985 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] H.Fujiki, M.Suganuma: "Tumor promotion by inhibitors of protein phosphatases 1 and 2A ; the okadaic acid class of compounds" Adv. Cancer Res.61. 143-194 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] R.J.Quinn, H.Fujiki, et al.: "The conserved acid binding domain model of inhibitors of protein phosphatases 1 and 2A : Molecular modeling aspects" Biomed.Chem.Lett.6. 1029-1034 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] H.Y.Li, H.Fujiki, et al.: "Echinoclasterol sulfate phenetylammonium salt, a unique steroid sulfate from the marine sponge, echinoclathrea subhispida additional inhibitors of protein phosphatases 1 and 2A, from the marine sponge Discondermia Calyx" Tetrahedron Lett.34. 5733-5736 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Kanazawa, N.Fusetani, et al.: "Cylindramide : cytotoxic, tetramic acid lactam from the marine sponge Halichondria cylindrata Tanita & Hoshino" Tetrahedron Lett.34. 1065-1068 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Fusetani: "Antifungal brominated C18 acetylenic acids from the marine sponge, Petrosia volcano Hoshino" Tetrahedron Lett.49. 1203-1210 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Nakao, N.Fusetani, et al.: "Toxadocial A : novel thrombin inhibitor from the marine sponge Toxadocia cylindrica" Tetrahedron Lett.34. 1511 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Fusetani: "Cinachyrolide A : a potent cytotoxic macrolide possessing two spiro ketals from marine sponge Cinachyra sp." J.Am.Chem.Soc.115. 3977-3981 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] H.Yagi, N.Fusetani, et al.: "Purpuramines A-I, new bromotyrosine-derived metabolites from the marine sponge Psammaplysilla prupurea" Tetrahedron. 49. 3749-3754 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Fusetani: "Isolation and structure elucidation of erylusamine B, a new class of marine natural products, which blocked an IL-6 receptor, from the marine sponge Erylus placenta Thiele" Tetrahedron Lett.34. 4067-4070 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Fusetani: "Bioactive sponge peptides" Chem.Rev.93. 1793-1806 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Matsunage, N.Fusetani, et al.: "Cribrochalinamine oxides A and B, antifungal beta-substituted pyridines with an azomethine N-oxide from a marine sponge Cribrochalina sp." Tetrahedron Lett.34. 5953-5954 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] H.Fujiki, T.Ohta, et al.: Gazzetta Chimica Italiana. Significant marine natural products in cancer research, 309-316 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary

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Published: 1993-04-01   Modified: 2016-04-21  

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