Analysis of the mechanisms of the actions of DIF-1 and its derivatives, anti-tumor agents isolated from Dictyostelium
| Project/Area Number |
17590115
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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 |
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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| 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 Medicine, Professor, 医学部, 教授 (70108992)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Dictyostelium / DIF / anti-tumor agent / PDE1 / Zinc / Dictyostelium / がん |
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| 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. Furthermore, we have shown that calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is a pharmacological and specific target of DIF-1. Yet, the mechanisms underlying the actions of DIF-1 in mammalian cells remain to be elucidated.
In the present study;
1.We synthesized 30 DIF derivatives, and analyzed their chemical structure-effect relationship in vitro, and found some potent anti-tumor agents.
2.We are attempting to isolate DIF-resistant HEK293 cell lines, using RNAi technique, to elucidate the mechanism of the action of DIFs.
3.During the course of the study on DIF toxicity, we have found that DIF-1 promote glucose metabolism in mammalian cells.
4.We have shown that DIF-1 induces stalk cell formation via increases in cytoplasmic calcium and proton in Dictyostelium discoideum.
5.We have isolated several new substances that have pharmacological activities.
6.We happened to find that zinc ions inhibit calcineurin activity in vitro and shown that zinc ions suppress mitogen-activated IL-2 production in Jurkat T cell.
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Report
(3 results)
Research Products
(27 results)
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[Journal Article] Structural requirements of Dictyostelium differentiation-inducing factors for their stalk-cell-inducing activity in Dictyostelium cells and anti-proliferative activity in K562 human leukemic cells.2005
Author(s)
Gokan, N., Kikuchi, H., Nakamura, K., Oshima, Y., Hosaka, K., Kubohara, Y.
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Journal Title
Biochem.Pharmacol. 70
Pages: 676-685
Related Report
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[Journal Article] Dictyopyrones, novel α-pyronoids isolated from Dictyostelium spp., promote stalk cell differentiation in Dictyostelium discoideum.2005
Author(s)
Arai, A., Goto, Y., Hasegawa, A., Hosaka, K., Kikuchi, H., Oshima, Y., Tanaka, S., Kubohara, Y.
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Journal Title
Differentiation 73
Pages: 377-384
Related Report
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[Journal Article] Isolation and synthesis of a new aromatic compound, brefelamide, from Dictyostelium cellular slime molds and its inhibitory effect on proliferation of astrocytoma cells.2005
Author(s)
Kikuchi, H., Saito, Y., Sekiya, J., Okano, Y., Saito, M., Nakahata, H., Kubohara, Y., Oshima, Y.
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Journal Title
J.Org.Chem. 70
Pages: 8854-8858
Related Report
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