| Project/Area Number |
09357020
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
医薬分子機能学
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| Research Institution | University of Tokushima |
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Principal Investigator |
TERADA Hiroshi Fac.Pharm.Sci., Univ.Tokushima, Professor, 薬学部, 教授 (00035544)
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| Co-Investigator(Kenkyū-buntansha) |
HORI Hitoshi Fac.Eng., Univ.Tokushima, Professor, 工学部, 教授 (90119008)
YAMAZAKI Naoshi Fac.Pharm.Sci., Univ.Tokushima, Assistant professor, 薬学部, 助手 (20271083)
SHINOHARA Yasuo Fac.Pharm.Sci., Univ.Tokushima, Associate professor, 薬学部, 助教授 (60226157)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥31,200,000 (Direct Cost: ¥31,200,000)
Fiscal Year 2000: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1999: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1998: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1997: ¥12,600,000 (Direct Cost: ¥12,600,000)
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| Keywords | type II hexokinase / energy metabolism / oxidative phosphorylation / glycolysis / anti-tumor drugs / porin / type 1 glucose transporter / mitochondria / ヘキソキナーゼ / HIF / 転写阻害剤 |
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| Research Abstract |
Various chemicals have been established as potential candidates of anticancer drugs. However, due to their low selective toxicity against tumor cells, most of them show strong side effects. To overcome this problem, chemicals showing highly selective toxicity against tumor cells must be established. To explore desirable candidates of anti-tumor drugs, in this study, we tried to characterize the energy metabolism specifically held in tumor cells. As a result, following results were obtained.
1. We found that the transcript level of type II hexokinase was remarkable in malignant tumor cells. Quantitative analysis showed that the level of its expression in tumor cells were as high as 2.5 fmol/mg poly(A)^+ RNA.
2. We next explored under which condition the expression of type II hexokinase become remarkable. As a result, transcript level of type II hexokinase was remarkable when AH130 cells were grown in an abdominal cavity of rats. However, when this cell line was grown in culture dishes, the transcript level of type II hexokinase was remarkably lower than that observed with ascites cells. These results indicate that the transcript level of type II hexokinase could be changes accompanied by changes in culture conditions.
3. To understand how such remarkable change is caused, we examined possible involvement of hypoxia and serum stimulation. As a result, gene expression of type II hexokinase was remarkably elevated by serum stimulation.
Based on these results, we concluded that the metabolic pathway of sugar in tumor cells could be changed accompanied by changes in their growth conditions and that this change is mainly mediated by serum responsive factor. These findings are very helpful for design and development of new anti-tumor drugs. We are now exploring candidate compounds which specifically suppress the growth of tumor cells.
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