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MECHANISM OF INDUCTION OF DIFFRENTIATION INLEUKEMIA CELLS BY TOPOISOMERASE INHIBITORS

Research Project

Project/Area Number 03671063
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionSHOWA UNIVERSITY

Principal Investigator

NAKAYA Kazuyasu  SHOWA UNIVERISTY,SCHOOL OF PHARMACEUTICAL SCIENCES, 薬学部, 教授 (40053855)

Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsDIFFERENTIATION / LEUKEMIA CELLS / CAMPTOTHECIN / RETINOIC ACID / BUFALIN / APOPTOSIS / TOPOISOMERASE INHIBITOR / TOPOISOMERASE / 白血病 / 分化 / トポイソメラ-ゼ / トポイソメラ-ゼ阻害剤
Research Abstract

Camptothecin and VP16 are known as inhibitors for topoisomerase I and II, respectively. We have previously found that these topoisomerase inhibitors and bufalin, an active principle of the Chinese medicine chan'su, induce differentiation of various kinds of human leudemia cell lines. The present study was undertaken to investigate the mechanism og the induction of differintiation in human leukemia cells by these differentiationinducers. Bufalin indirectly inhibits topoisomerase II in leukemia HL60 cells via signal transduction pathway. Therefore, bufalin is classified as a movel inhibitor of topoisomerasa II.All these topoisomerase inhibitors arresred the cell cycle of leukemia cells at the G2/M phase. Synergistic effects on the induction of differentiation in leukemia cells were observed by combination of bufalin with camptothecin or VP16. Combination of retinoic acid, clinically used as a drug for acute promyelocytic leukemia, with camptothecin or VP16 also showed marked synergistic effects on the differentiation of leukemia cells. Although camptothecin and VP16 are known as inducers of apoptosis, we found that bufalin can also induce apoptosis in HL60 cells when used at higher concentrations than used for inducing differentiation. Synergistic effects on the induction of apoprosis were observed by combined teratment of camptothecin with VP16, retinoic acid with VP16, or bufalin with retinoic acid. These results suggest the usefulness of these topoisomerase ingibitors for diffentiation-apoptosis inducing therapy for cancer.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Yongkui Jing: "Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth inhibition and induction of differenti-ation of leukemia HL-60 cells." Leukemia Research. (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yongkui Jing: "The selective inhibitory effect of bufalin on growth of human tumor cells in vitro:Association with the induction of apoptosis." Jpn.J.Cancer Res.85. (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yongkui Jing, Sachiko Hashimoto, Shigeo Nakajo and Kazuyasu Nakaya: "Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth ingibition and induction of differentiation of leukemia HL-60 cells." Leukemia Res.in press. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] "The selective inhibitory effect of bufalin on growth of human tumor cells in vitro : Association with the induction of apoptosis in leukemia HL-60 cells." Jpn. J.Cancer Res.85-6 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yongkui Jing: "Topoisomerase inhibitors potentiate the effect of retinoic acid on cell growth inhibition and induction of differentiation of leukemia HL-60 cells." Leukemia Research. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yongkui Jing: "The selective inhibitory effect of bufalin on growth of human tumor cells in vitro:Association with the induction of apoptosis." Jpn.J.Cancer Res.85. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 中谷 一泰: "Topoisomera inhibitors have potent differentiation-inducing activity for human and mouse myeloid leukemia cells." Jpn.J.Cancer Res.82. 184-191 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 中谷 一泰: "Topoisomerase Inhibitors Have Potent Differentiationーinducing Activity for Human and Mouse Myeloid Leukomia Cells." Jpn.J.Cancer Res.82. 184-191 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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