| Project/Area Number |
16590105
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Gunma University |
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Principal Investigator |
HOSAKA Kohei Gunma University, Department of Medicine, professor, 医学部, 教授 (70108992)
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| Co-Investigator(Kenkyū-buntansha) |
KUBOHARA Yuzuru Gunma University, Institute for Molecular and Cellular Regulation, associate professor, 生体調節研究所, 助教授 (00221937)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | cellular slime mold / differentiation-inducing factor / DIF-1 / DIF-1 like factors / leukemia cells / growth inhibitory activity / pharmacological specific target / Dictyopyrones / DIF様因子 / 増殖抑制 / Dictiostelium mucoroides / 4-methyl-5-n-propylbenzene-1,3-diol / キノコ / ハロゲン化化合物 |
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| Research Abstract |
The differentiation-inducing factor-1 (DIF-1) is a signal molecule that induces stalk cell differentiation in the cellular slime mold Dctyostelium discoideum. On the other hand, it has been shown that DIF-1 exhibits anti-tumor activities, inhibition of cell growth (G1 arrest) and induction of cell differentiation or cell differentiation, and induction of apotosis, depending on the concentration of the drug. But the precise signaling system of DIF-1, including the target molecule(s), has been unknown.
The results obtained in this project were as follows :
i) DIF-1-induced growth arrest of K562 leukemia cells involved the reduction of ERK 1/2 activity.
ii) Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) was a pharmacological specific target of DIF-1.
iii) Dictyopyrones, novel α-pyronoids isolated from Dctyostelium spp., promoted stalk cell differentiation in Dctyostelium discoideum.
iv) A new aromatic compound, brefelamide(4-methyl-5-n-propylbenzene-1,3-diol), from Dicyostelium cellular slime molds showed the inhibitory effect on the proliferation of astrocytoma cells.
v) New DIF-1 like factors were isolated from mature fruiting bodies of Armillaria tabescens and Laetiporus sulphureus.
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