| Project/Area Number |
06672239
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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 |
医薬分子機能学
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| Research Institution | Showa University |
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Principal Investigator |
NAKAYA Kazuyasu Showa University, Professor, 薬学部, 教授 (40053855)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Yutaka Showa University, Research Associate, 薬学部, 助手 (10255862)
|
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| Project Period (FY) |
1994 – 1995
|
| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | leukemia / differentiation / apoptosis / combined effect / apoptosis-inducer / differentiation-inducer |
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| Research Abstract |
We have found that geranylgeraniol (GGO) is a potent inducer of apoptosis in various tumor cell lines including human myeloid leukemia, lymphoblastic, and adenocarcinoma. Upon treatment of HL-60 cells with 50 muM GGO, 85% of DNA was fragmented in 3 h. [^3H] GGO was taken up by HL-60 cells in 3 h and was incorporated into several proteins with molecular masses from 10.5 to 20.1 kDa, suggesting these proteins were geranylgeranylated. The expression of c-myc and bc1-2 decreased significantly within 3 h.
To explore agents for differentiation-apoptosis therapy of leukemia, various combinations of differentiation-and apoptosis-inducers were examined for the strongest apoptosis-inducing activity for human HL-60 cells. The strongest apotosis-inducing acitvity on HL-60 cells were obtained by combining with retinoic acid, bufalin, and VP16. Administration of the combination of retinoic acid, bufalin, and VP16 to mice inoculated with HL-60 cells was makedly effective in prolongation of survival.
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