| Project/Area Number |
15590123
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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 Health Sciences, 医学部, 教授 (70108992)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Dictyostelium / DIF-1 / PDE1 / Anti-tumor drug / Erk / K562 / Cancer |
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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. 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).
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