| Project/Area Number |
02671000
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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 |
Biological pharmacy
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TERADA Hiroshi Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00035544)
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| Co-Investigator(Kenkyū-buntansha) |
HORI Hitoshi Faculty of Engineering, Associate Professor, 工学部, 助教授 (90119008)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Cyclopentendione derivatives / Bioenergy / Anti-tumor activity / Mitochondria / Anti-tumor agents / シクロペンテンジオン / リン酸輸送担体 / 窒素キャビテ-ション |
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| Research Abstract |
For development of new types of anti-tumor agents, it is important to search for chemical compounds that recognize a "specific state" of tumor cells that is markedly different from that of normal cells. Energy transducing-membrane systems such as mitochondria are good models to use in examining this possibility, because the state of the membrane changes according to their energy state. We have already found that cyclopentendiones are potent and specific inhibitors of the transport of inorganic phosphate that is indispensable for ATP synthesis. Thus, we used mitochondria from normal rat liver cells, and tumor cells that both produce ATP to study what changes took place on their membranes under various conditions, and the effects of nucleophilic cyclopentendiones on them. We analyzed the mechanisms and the effects of the inhibitors of energy transduction on mitochondria from normal and tumor cells. The results were as follows.
1)We succeeded in preparation of highly intact mitochondria from the tumor cell line AH130.
2)We developed a new type of TPP^+-selective electrode of small size which showed high sensitivity for TPP^+. Using this electrode for analysis of the energy state of mitochondria, we succeeded in finding several analogs of cyclopentendiones that inhibited energy transduction in tumor cells.
3)Furthermore, we found that some analogs of cyclopentendione inhibited phosphate transporter protein more efficiently in the tumor mitochondria than in normal mitochondria.
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