| Project/Area Number |
13670465
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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 |
内科学一般
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| Research Institution | SAPPORO MEDICAL UNIVERSITY |
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Principal Investigator |
ADACHI Masaaki SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE ASOCIATE PROF., 医学部・大学院・医学研究科, 助教授 (70240926)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Kohzoh SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE PROF., 医学部・大学院・医学研究科, 教授 (60117603)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Histone acetylation / Transcriptional activation / Apoptosis / p300 / CBP / Histone acetyltransferase / Cancer therapy / HDAC |
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| Research Abstract |
1. Biological effects of aceylated peptides
HDAC inhibitors have a core domain which mimicks acetylated lysines, and bind to HDAC directly. We thus explored whether peptides carrying acetylated lysines can inhibit HDAC and introduce apoptosis in cancer cells. So far, our several peptides cannot have sufficient effects on HDAC. We are now frying other peptides.
2. HDAC inhibitor-mediated cancer therapy
HDAC inhibitors alone introduce apoptosis in a variety of carcinoma cells. These drugs are promising anticancer agents. However, phase I clinical trial revealed that there are some adverse effects and thus we should consider how their administration doses are reduced. In this regard, we are now investigating their combination therapy. To date, we found that HDAC inhibitors can be strongly effective with some technique. We are now preparing a new manuscript and have already submitted this patent. Our data strongly suggest that our technique can reduce required doses for their anticancer activity.
3. Biological effect of HAT overexpressoin using reporter assays
We transfected p300 or CBP-expression vectors into several cancer cells. Using a luciferase-reporter assay, we found that there are some difference in their transcriptional activation. Especially, both genes strongly activate AP-1 transcription. This strongly suggest that p300 and CBP are tightly linked to MEK/ERK pathway. We thus investigating this mechanism.
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