• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2004 Fiscal Year Final Research Report Summary

Analysis of the actions and the action mechanism of DIF, an anti-tumor agent isolated from a soil microorganism

Research Project

Project/Area Number 15590123
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionGunma University

Principal Investigator

KUBOHARA Yuzuru  Gunma University, Institute for Molecular and Cellular Regulation, Associate Professor, 生体調節研究所, 助教授 (00221937)

Co-Investigator(Kenkyū-buntansha) KOJIMA Itaru  Gunma University, Institute for Molecular and Cellular Regulation, Professor, 生体調節研究所, 教授 (60143492)
HOSAKA Kohei  Gunma University, School of Health Sciences, 医学部, 教授 (70108992)
Project Period (FY) 2003 – 2004
KeywordsDictyostelium / DIF-1 / PDE1 / Anti-tumor drug / Erk / K562 / Cancer
Research Abstract

The cellular slime mould Dictyostelium discoideum is thought to be an excellent model organism for the study of cell and developmental biology because of its simple pattern of development. The differentiation-inducing factor-1(DIF-1) was originally identified as signal molecules that induce stalk cell differentiation in D.discoideum. On the other hand, we have shown that DIF-1 exhibits strong anti-proliferative activities and occasionally induce cell differentiation in mammalian cells. Yet, the mechanisms underlying the actions of DIF-1 in mammalian cells remain to be elucidated.
In the present study, we have shown that ;
1)DIF-1 inactivates STAT3 in gastric cancer cells via MEK/ERK pathway (Kanai et al.2003),
2)DIF-1 inhibits the expression of cyclins D/E and the phosphorylation of retinoblastoma protein (pRb) in K562 cells (Akaishi et al.2004), and
3)calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is a pharmacological and specific target of DIF-1 (Shimizu et al.2004).
4)Furthermore, in order to assess the chemical structure-effect relationship of DIF derivatives and to develop useful agents, we synthesized many analogues of DIF-1 and investigated their stalk-cell-inducing activity anti-proliferative activity in human leukemia K562 cells. We have then found some potent anti-leukemic agents (submitted).
5)During the course of this study, we happened to found that zinc ions inhibit calcineurin activity in vitro (Takahashi et al.2003).

  • Research Products

    (13 results)

All 2004 2003

All Journal Article (12 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Differentiation-inducing factor-1-induced growth arrest of K562 leukemia2004

    • Author(s)
      Akaishi E, Narita T, Kawai S, Miwa Y, Sasakura T, Hosaka K, Kiyohara Y
    • Journal Title

      European Journal of Pharmacology 485

      Pages: 21-29

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Calmodulin-dependent cyclic nucleotide phosphodiesterase(PDE1) is a pharmacological target of differentiation-inducing factor-1, an anti-tumor agent isolated from Dictyostelium.2004

    • Author(s)
      Shimizu K, Murata T, Tagawa T, Takahashi K, Ishikawa R, Abe Y
    • Journal Title

      Cancer Research 64

      Pages: 2568-2571

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Structural requirements of dictyopyrones isolated from Dictyostelium spp.in the regulation of Dictyostelium development and in anti-leukemic activity.2004

    • Author(s)
      Kikuchi H, Sasaki K, Sekiya J, Maeda Y, Amagai A, Kubohara Y, Oshima Y
    • Journal Title

      Bioorg.Med.Chem. 12

      Pages: 3203-3214

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differentiation-inducing factor-1-induced growth arrest of K562 leukemia cells involves the reduction of ERK1/2 activity.2004

    • Author(s)
      Akaishi, E., Narita, T., Kawai, S., Miwa, Y, Sasaguri, T., Hosaka, K., Kubohara, Y.
    • Journal Title

      Eur.J.Pharmacol. 485

      Pages: 21-29

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is a pharmacological target of differentiation-inducing factor-1, an anti-tumor agent isolated from Dictyostelium.2004

    • Author(s)
      Shimizu, K., Murata, T., Tagawa, T., Takahashi, K., Ishikawa, R., Abe, Y, Hosaka, K., Kubohara, Y.
    • Journal Title

      Cancer Res. 64

      Pages: 2568-2571

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Structural requirements of dictyopyrones isolated from Dictyostelium spp. in the regulation of Dictyostelium development and in anti-leukemic activity.2004

    • Author(s)
      Kikuchi, H., Sasaki, K., Sekiya, J., Maeda, Y., Amagai, A., Kubohara, Y., Oshima, Y.
    • Journal Title

      Bioorg.Med.Chem. 12

      Pages: 3203-3214

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dictyostelium differentiation-inducing factor-3 activates glycogen synthase kinase-3β and degrades cyclin D1 in mammalian cells.2003

    • Author(s)
      Takahashi-Yanaga F, Taba Y, Miwa Y, Kubohara Y, Watanabe Y, Hirata M, Morimoto S, Sasaguri T
    • Journal Title

      J.Biol.Chem. 278

      Pages: 9663-9670

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differentiation-inducing factor-1(DIF-1) inhibits STAT3 activity involved in gastric cancer cell proliferation via MEK-ERK dependent pathway.2003

    • Author(s)
      Kanai M, Konda Y, Nakajima T, Izumi Y, Nanakin A, Kanda N, Kubohara Y, Chiba T
    • Journal Title

      Oncogene 22

      Pages: 548-554

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Zinc inhibits calcineurin activity in vitro by competing with nickel.2003

    • Author(s)
      Takahashi K, Akaishi E, Abe Y, Ishikawa R, Tanaka S, Hosaka K, Kubohara Y
    • Journal Title

      Biochem.Biophys.Res.Commun. 307

      Pages: 64-68

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differentiation-inducing factor-1(DIF-1) inhibits STAT3 activity involved in gastric cancer cell proliferation via MEK-ERK dependent pathway.2003

    • Author(s)
      Kanai, M., Konda, Y., Nakajima, T., Izumi, Y, Nanakin, A., Kanda, N., Kubohara, Y., Chiba, T.
    • Journal Title

      Oncogene 22

      Pages: 548-554

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dictyostelium differentiation-inducing factor-3 activates glycogen synthase kinase-3β and degrades cyclin D1 in mammalian cells.2003

    • Author(s)
      Takahashi-Yanaga, F., Taba, Y., Miwa, Y., Kubohara, Y., Watanabe, Y., Hirata, M., Morimoto, S., Sasaguri, T.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 9663-9670

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Zinc inhibits calcineurin activity in vitro by competing with nickel.2003

    • Author(s)
      Takahashi, N., Akaishi, E., Abe, Y, Ishikawa, R., Tanaka, S., Hosaka, K., Kubohara, Y.
    • Journal Title

      Biochem.Biophys.Res.Commun. 307

      Pages: 64-68

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] PDE1阻害剤2004

    • Inventor(s)
      久保原 禅, 保坂 公平, 清水 香澄, 村田 琢, 田川 俊郎
    • Industrial Property Rights Holder
      群馬大学
    • Industrial Property Number
      特願2004-108018
    • Filing Date
      2004-03-31
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2006-07-11  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi