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Studies on The Low Toxic Antitumor Promoting Activities of Natural Products in Celastraceae Plants.

Research Project

Project/Area Number 05453183
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Chemical pharmacy
Research InstitutionUniversity of Tokushima

Principal Investigator

TAKAISHI Yoshihisa  University of Tokushima, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60035558)

Co-Investigator(Kenkyū-buntansha) NAKANO Kimiko  University of Tokushima, Faculty of Pharmaceutical Sciences, Research Assistant, 薬学部, 助手 (20136279)
SHISHIDO Kozo  University of Tokushima, Faculty of Pharmaceutical Sciences, Proffesor, 薬学部, 教授 (20006349)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordssesquiterpene / antitumor promoter / Celastraceae / Tripterygium / two-stage carcinogenic test / Triptogelin / triptofordin / TPA / トリテルペン / 植物成分 / 植物組織培養
Research Abstract

Recently, studies on antitumor promoting activities have been reported detailing the inhibitory effects of several natural products on 12-O-tetradecanoylphorbol-13-acetate(TPA)induced Epstein-Barr virus early antigen(EBV-EA)activation. Tripterygium wilfordii Hook fil.has been used as an anticancer drug in China for hundreds of years. We have been studying the sesquiterpene constituents of some Celastraceae plants.We isolated about 50 new compounds from T.wilfordii Hook fil.var.regelii and Euonymus sieboldianus.
To search for possible antitumor pormoters, we examined the inhibitory tendency of these compounds on EBV-EA activation. Some of these sesquiterpenes were observed to significantly inhibit the EBV-EA activation allow doses. Next, we attempted to test the cytotoxicity of these compounds, because it is important to develop a reagent for chemoprevention against cancer. Several compounds did not show any cytotoxicity. Above findings indicate that these compounds might be valuable antitumor promoters.
Next, we tried to test in vivo two-stage carcinogenic test of mouse skin. Triptogelin A-1, one of the active compounds, exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. Furthermore, triptogelin A-1 showed inhibitory effects in two stage carcinogenesis test in mouse lung.
We evaluated sesquiterpenes for their antiviral activities, one of them, triptofordin C-2, was found to be active against herpes simplex virus type I and human cytomegalovirus. We suggest possible mechanisms of action of the compound.We also isolated new compounds from Celastraceae plants.These findings ndicated that data focus attention on possible exploitation of information for cancer preventive agent development.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Takaishi,Y.,Ujita,K.,Tokuda,H.,Nishino,H.,Iwashima,A.,Fujita,T.: "Inhibitory Effects of Dihydroagarofuran Sesquiterpenes on Epstein Barr Virus Activity" Cancer Letters. 65. 19-26 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ujita,K.,Takaishi,Y.,Tokuda,H.,Nishino,H.,Iwashima,A.,Fujita,T.: "Inhibitory Effects of Triptogelin A-1 on 12-O-Tetradecanoylphorbol-13-acetate-Induced Skin Tumor Promotion" Cancer Letters. 63. 129-133 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takaishi,Y.,Ohshima,S.,Nakano,K.,Tomimatsu,T.,Tokuda,H.,Nishino,H.,Iwashima,A.: "Structures of Sesquiterpene Polyol Esters from Celastrus stephanotifolius with Potential Tumor-Promotion Iihibitory Activity" J.Natural Products. 56. 815-824 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hayashi,K.,Hayashi,T.,Ujita,K.,Takaishi,Y.: "Characterization of Antiviral Activity of Sesquiterpene,Triptofordin C-2" J.Antimicrob.Chemotherapy. (submitted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawazoe,K.,Shimogai,N.,Takaishi,Y.,K.S.Rao.,Imakura,Y.: "Four Novel Stilben Derivatives from Salacia lehmbachii" Phytochemistry. (submitted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tokuda,H.,Ujita,K.,Takaishi,Y.,Fujita,T.,Nishino,H.: "Inhibitory Effect of Triptogelin A-1 in Two-stage Lung Carcinogenesis in the Mouse" Cancer Letters.(submitted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takaishi, Y., Ujita, K., Tokuda, H., Nishino, H., Iwashima, A.and Fujita, T.: ""Inhibitory Effects of Dihydroagarofuran Sesquiterpenes on Epstein Barr Virus Activity"" Cancer Letters. 65. 19-26 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ujita, K., Takaishi, Y., Iida, A.and Fujita, T.: ""Euonydin A-1-A-5, Sesquiterpene Esters from Euonymus sieboldianus"" Phytochemistry. 31. 1289-1292 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takaishi, Y., Aihara, F., Tamai, S., Nakano, K.and Tomimatsu, T.: ""Sesquiterpene Esters from Triptergium wilfordii"" Phytochemistry. 31. 3943-3947 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ujita, K., Takaishi, Y., Tokuda, H., Nishino, H., Iwashima, A.and Fujita, T.: ""Inhibitory Effects of Triptogelin A-1 on 12-O-Tetradecanoylphorbol-13-acetate-Induced Skin Tumor Promotion" Cancer Letters. 63. 129-133 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takaishi, Y., Ohsima, S., Nakano, K., Tomimatsu, T., Tokuda, H., Nishino. H.and Iwashima, A.: ""Structures of Sesquiterpene Polyol Esters from Celastrus stepanotifolius with Potential Tumor-Promotion Inhibitory Activity"" J.Natural Products. 56. 815-824 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hayashi, K., Hayashi, T., Ujita.K.and Takaishi, Y.: ""Characterization of Antiviral Activity of Sesquiterpene, Triptofordin C-2"" J.Antimicrob Chemotherapy. submitted. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawazoe, K., Shimogai, N., Takaishi, Y., K.S.Rao and Imakura Y.: " "Four Novel Stilben Derivatives from Salacia lehmbachii"" Phytochemistry. submitted. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tokuda, H., Ujita, K., Takaishi, Y., Fujita, T.and Nishino, H.: ""Inhibitory effect of triptogelin A-1 in two stage lung carcinogenesis in the mouse"" Cancer Letters. submitted. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takaishi, Y. et al.: "Inhibitory Effects of Dihydroagarofuran Sesquiterpenes on Epstein Barr Virus Activity" Cancer Letters. 65. 19-26 (1992)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takaishi, Y. et al.: "Sesquiterpene Esters from Tripterygium wilfordii" Phytochemistry. 31. 3943-3947 (1992)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takaishi, Y. et al.: "Structures of Sesquiterpene Polyol Esters from Celastrus stepanotifolius with Potetial Tumor-Promotion Inhibitory" J. Natural Products. 56. 815-824 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ujita, K. et al.: "Inhibitory Effects of Triptogelin A-1 on 12-0-Tetradeca-noylphorbol-13-acetate Induced Skin tumor Promotion" Cancer Letters. 63. 129-133 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] H.Sasa,et al.: "Structur al Basis of Potent Antiperoxidation Actiuity of The Triterpene Celastrol in Mitochondria" Free.Radical Biology & Medicine. 17. 201-207 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Takaishi et.al.: "Inhibitory effects of triptogelin A-1 on 12-O-tetradecanoyphorbol-13-acetate-induced skin tumor promotion" Cancer letters. 68. 129-133 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Takaishi et.al.: "Structures of Sesquiterpene Polyol Esters from Celastrus stephanotifolius with potential Tumor-promotion Inhibitory Activity" J.Natural Products. 56. 815-824

    • Related Report
      1993 Annual Research Report

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

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