| Project/Area Number |
63580118
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | Mie University |
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Principal Investigator |
HIBASAMI Hiroshige Mie University, College of Medical Sciences, professor, 医療技術短期大学部, 教授 (60024642)
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| Co-Investigator(Kenkyū-buntansha) |
NAKASHIMA Kunio Mie University, Department of Biochemistry, professor, 医学部, 教授 (40022800)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1989: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1988: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Growth inhibition / Polyamine biosynthesis / Spermidine / Spermine / Leukemia cells / P388 leukemia / ポリアミン生合阻害 / 癌細胞増殖 / 癌の転移 / ポリアミン合成阻害剤 |
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| Research Abstract |
The polyamine biosynthesis pathway is likely to be an important target for the design of chemotherapeutic agents. The concept of inhibition of polyamine biosynthesis as treatment for cancer is based on a greatly increased production of the polyamines, spermidine and spermine, in various types of cancer. The biochemical and biological consequences of polyamine deficiency induced by inhibitors of polyamine-synthesizing enzymes include arrest of DNA synthesis and of tumor growth. Efficient retardation of tumor cell growth has been obtained by the inhibitors to block the syntheses of spermidine and spermine. Among these inhibitors, MGBG is a well-known potent competitive inhibitor of AdoMetDC, depleting dec AdoMet as a substrate for spermidine and spermine synthases. However, this compound has turned out to possess paradoxical diamine oxidase-inhibiting and Ado MetDC-stabilizing activities and severe undesirable side effects These additional properties of MGBG hamper its wide range use in in vivo and clinical studies.
In the present study, we have synthesized a new compound Methylglyoxal-bis(cyclopentylamidinohydrazone) to inhibit AdoMetDC, spermine synthase, and spermidine synthase, simultaneously. The compound effectively depressed cellular contents of spermine as well as those of spermidine, and exhibited relatively good antitumor effect.
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