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Combined effects of differentiation-apoptosis inducers on mice inoculated with human leukemia cells.

Research Project

Project/Area Number 06672239
Research Category

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

Allocation TypeSingle-year Grants
Research Field 医薬分子機能学
Research InstitutionShowa University

Principal Investigator

NAKAYA Kazuyasu  Showa University, Professor, 薬学部, 教授 (40053855)

Co-Investigator(Kenkyū-buntansha) MASUDA Yutaka  Showa University, Research Associate, 薬学部, 助手 (10255862)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsleukemia / differentiation / apoptosis / combined effect / apoptosis-inducer / differentiation-inducer
Research Abstract

We have found that geranylgeraniol (GGO) is a potent inducer of apoptosis in various tumor cell lines including human myeloid leukemia, lymphoblastic, and adenocarcinoma. Upon treatment of HL-60 cells with 50 muM GGO, 85% of DNA was fragmented in 3 h. [^3H] GGO was taken up by HL-60 cells in 3 h and was incorporated into several proteins with molecular masses from 10.5 to 20.1 kDa, suggesting these proteins were geranylgeranylated. The expression of c-myc and bc1-2 decreased significantly within 3 h.
To explore agents for differentiation-apoptosis therapy of leukemia, various combinations of differentiation-and apoptosis-inducers were examined for the strongest apoptosis-inducing activity for human HL-60 cells. The strongest apotosis-inducing acitvity on HL-60 cells were obtained by combining with retinoic acid, bufalin, and VP16. Administration of the combination of retinoic acid, bufalin, and VP16 to mice inoculated with HL-60 cells was makedly effective in prolongation of survival.

Report

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

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Itaru SAKAI: "Novel role of vitamin K2 : a potent inducer of differentiaionof various human myeloid leukemia cell lines." Biochem.Biophys.Res.Commun.205. 1305-1310 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hidekazu OHIZUMI: "Geranylgeraniol is a potent inducer of apoptosis in tumor cells." J.Biochem.117. 11-13 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Itaru Sakai, Schiko Hashimoto, Madoka Yoda, Takayuki Hida, Shigemitsu Osawa, Shigeo Nakajo and kazuyasu Nakaya: "Role of vitamin K2 ; a potent inducer of differentiation of various human myeloid leukemia cell lines" Biochem.Biophys.Res.Commun.205. 1305-1310 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hidekazu Ohizumi, Yutaka Masuda, Shigeo Nakajo, Itaru Sakai, Shigemitsu Osawa, and Kazuyasu Nakaya.: "Geranylgeraniol is a potent inducer of apoptosis in tumor cells." J.Biochem.117. 11-13 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Itaru SAKAI: "Novel role vitmin K2 : a potent inducer of differentiaionof various human myeloid leukemia cell lines" Biochem. Biophys. Res. Commun.205. 1305-1310 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hidekazu OHIZUMI: "Geranylgeraniol is a potent inducer of apoptosis in tumor cells." J. Biochem.117. 11-13 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Itaru SAKAI: "Novel role of vitamin K2:a potent inducer of differentiaionof various human myeloid leukemia cell lines." Biochem.Biophys.Res.Commun.205. 1305-1310 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hidekazu OHIZUMI: "Geranylgeraniol is a potent inducer of apoptosis in tumor cells." J.Biochem.117. 11-13 (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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