Novel small-molecule SIRT1 inhibitors induce cell death in leukaemia cells
| Project/Area Number |
24591413
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Fukuoka University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SUZUKI Takayoshi 京都府立医科大学, 医学部, 教授 (90372838)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | ATL / HTLV-1 / SIRT1 |
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| Outline of Final Research Achievements |
Adult T-cell leukaemia/lymphoma (ATL) is an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukaemia virus (HTLV)-1. We previously reported that ATL patients had significantly higher SIRT1 protein levels than healthy controls. Here, we demonstrate that two novel small-molecule SIRT1 inhibitors, NCO-01/04, reduced cell viability and enhanced apoptotic cells in peripheral blood monocyte cells of patients with acute ATL, which has a poor prognosis. Interestingly, NCO-01/04 increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation as well as autophagy. Thus, NCO-01/04 simultaneously caused caspase activation and autophagy. These results suggest that NCO-01/04 is highly effective against ATL cells in caspase-dependent or -independent manners with autophagy, and that its clinical application might improve the prognosis of patients with this fatal disease.
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheumatoid arthritis.2013
Author(s)
Akimoto M, Yunoue S, Otsubo H, Yoshitama T, Kodama K, Matsushita K, Suruga Y, Kozako T, Toji S, Hashimoto S, Uozumi K, Matsuda T, Arima N.
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Journal Title
Mod Rheumatol.
Volume: 23
Issue: 1
Pages: 19-27
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Vasohibin induces prolyl hydroxylase-mediated degradation of hypoxia-inducible factor-1α in human umbilical vein endothelial cells.2012
Author(s)
Kozako T, Matsumoto N, Kuramoto Y, Sakata A, Motonagare R, Aikawa A, Imoto M, Toda A, Honda S, Shimeno H, Soeda S.
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Journal Title
FEBS Lett.
Volume: 586
Issue: 7
Pages: 1067-1072
DOI
Related Report
Peer Reviewed
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