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1991 Fiscal Year Final Research Report Summary

Developmental research of selective toxic anticancer drug and cancer-diagnose drug targeting cancer mitochondria

Research Project

Project/Area Number 01880022
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field 代謝生物化学
Research InstitutionTokushima University

Principal Investigator

HIGUCHI Tomihiko  Tokushima University, Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (50035557)

Co-Investigator(Kenkyū-buntansha) YANAGI Yoshikazu  Sumitomo Pharmaceutical CO. LTD., Developmental Section of Medical Ddrugs, Head, 医薬開発部, 部長
Project Period (FY) 1989 – 1991
KeywordsAnticancer drug / Selective toxicity / Mitochondria / Anisotropic inhibitor / Cisplatin / Human brease cancer (MX-1)
Research Abstract

1. We found that 20 species of the anisotropic inhibitors of energy transductionin mitochondria, which are membrane-side specific inhibitors in mitochondrial inner membrane, had a lethal effect on both exponentially growl and, stationary phases of P388 and Sarcoma 180 cancer cells.
2. TZ3-4 and TZ3-13 had a dramatical effect on decreasing Sarcoma 180 transplanted into mice.
3. We developed a preparation method of intact mitochondria from human breast cancer (MX-1).
4. We demonstrated that cisplatin selectively inhibited the respiration in mitochondria prepared from human breast cancer (MX-1), but not those activities in mitochondria prepared from normal rat liver and heart.
The present findings indicate an extremely important possibility of development of selective toxic anticancer drug targeting human breast cancer'mitochondria.

  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] T.Oda: "Orientation of Chargerin II(A6L)in the ATP synthase of Rat Liver Mitochondria Determined with Antibodies Against Peptides of the Protein." Biochem.Biophys.Res.Commun.165. 449-456 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Muraguchi: "Stoichiometry of Chargerin II(A6L)in the H^+-ATP Synthase of Rat Liver Mitochondria" Biochem.Biophys.Res.Commun.168. 226-231 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] C.Tsurumi: "cDNA Cloning and Sequencing for the Import Precursor of Subunit B in H^+-ATP Synthase from Rat Mitochondria" Biochem.Biophys.Res.Commun.169. 136-142 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Higuti: "cDNA Cloning and Sequencing for the Import Precursor of Coupling Factor 6 in H^+-ATP Synthase from Rat Liver Mitochondria" Biochem.Biophys.Res.Commun.171. 1079-1086 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Yoshihara: "H^+-ATP Synthase from Rat Liver Mitochondria.A Simple,Rapid Purification Method of the Functional Complex and Its Characterization" Biochemistry. 30. 6854-6860 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] I.Inoue: "ATP-sensitive K^+ Channel in the Mitochondrial Inner Membrane" Nature. 352. 793-799 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Higuti: "Molecular Cloning of cDNA for the Import Precursor of Human Coupling Factor 6 of H^+-ATP Synthase in Mitochondria" Biochem.Biophys.Res.Commun.178. 793-799 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Higuti: "Molecular Cloning of cDNA for the Import Precursor of Human Subunit B of H^+-ATP synthase in Mitochondria" Biochem.Biophys.Res.Commun.178. 1014-1020 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] I.Inoue: "An ATP-sensitive K+Channel in the Membrane of Fused Giant Mitoplasts" J.Physiol.(1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Higuti: "The Molecular Structure,Function and Assembly of ATP Synthases(S.Marzuki,ed.)" Plenum Press, 273-280 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 樋口 富彦(分担): "生体を構成する高分子とその機能" 廣川書店, 237 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 樋口 富彦(分担): "「細胞・抗体・遺伝子の基礎実験法」ー蛋白質を中心として" 南江堂, (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 樋口 富彦(分担): "[細胞生物学" 廣川書店, (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Oda et al.: "Orientation of Chargerin II (A6L) in the ATP synthase of Rat Liver Mitochondria Determined with Antibodies against Peptides of the Protein." Biochem. Biophys. Res. Commun.165. 449-456 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Muraguchi et al,: "Stoichiometry of Chargerin II (A6L) in the H^+-ATP Synthase of Rat Liver Mitochondria" Biochem. Biophys. Res. Commun.168. 226-231 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] C. Tsurumi et al.: "cDNA Cloning and Sequencing for the Import Precursor of Subunit B in H^+-ATP Synthase from Rat Mitochondria" Biochem. Biophys. Res. Commun.169. 136-142 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Higuti et al.: "cDNA Cloning and Sequencing for the Import Precursor of Coupling Factor 6in H^+-ATP Synthase from Rat Liver Mitochondria" Biochem. Biophys. Res. Commun.171. 1079-1086 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Yoshihara et al.: "H^+-ATP Synthase from Rat Liver Mitochondria. A Simple, Rapid Purification Method of the Functional Complex and Its Characterization" Biochemistry. 30. 6854-6860 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] I. Inoue et al.: "ATP-sensitive K^+ Channel in the Mitochondrial Inner Membrane" Nature. 352. 244-247 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Higuti et al.: "Molecular Cloning of cDNA for the Import Precursor of Human Coupling Factor 6 of H^+-ATP Synthase in Mitochondria" Biochem. Biophys. Res. Commun.178. 793-799 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Higuti et al.: "Molecular Cloning of cDNA for the Import Precursor of Human Subunit B of H^+-ATP synthase in Mitochondria" Biochem. Biophys. Res. Commun.178. 1014-1020 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] I. Inoue et al.: "An ATP-sensitive K_+ Channel in the Membrane of Fused Giant Mitoplasts" J. Physiol.(1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Higuti et al.: Plenum Press. The Molecular Structure, Function and, Assembly of ATP Syntases (S. Mzrzuki, ed.), (Hydrophobic Protein, Chargering II, Purified from Rat Liver Mitochondria Is Encoded in the Unidentified Reading Frame A6L of Mitochondrial DNA), (1990)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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