Nicotinamide potentiates HDAC inhibitor-induced cytotoxicity in human breast cancer cells through DNA damage accumulation
| Project/Area Number |
24591923
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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 |
General surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
UEHARA NORIHISA 九州大学, 歯学研究科(研究院), 助教 (30368211)
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| Co-Investigator(Renkei-kenkyūsha) |
TSUBURA Airo 関西医科大学, 医学部, 教授 (90098137)
YOSHIZAWA Katsuhiko 関西医科大学, 医学部, 講師 (70548396)
KATAKURA Yoshinori 九州大学, 農学部, 准教授 (50264106)
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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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HDAC inhibitor / ニコチンアミド / 合成致死 / DNA損傷 / breast cancer / nicotinamide / DNA damage |
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| Outline of Final Research Achievements |
Poly(ADP-ribose) polymerases (PARPs) are nuclear protein that play a pivotal role in DNA single-strand breaks (SSB) repair pathway. Recently, PARP inhibitor has been employed as a novel therapeutic strategy to facilitate the cytotoxicity of DNA-damaging agents against cancer cells defective in homologous recombination repair through synthetic lethality. In the present study, we evaluated the effect of nicotinamide (NAM), an inhibitor of PARP-1 on the histone deacetylase inhibitor vorinostat-induced apoptosis in human breast cancer cells. When a NAM was combined with vorinostat, the dose of vorinostat required for apoptosis induction in MDA-MB-231 human breast cancer cells was markedly reduced, whereas normal human mammary epithelial cells exhibited resistance to vorinostat plus NAM treatment. Our results indicate that NAM may be a good candidate for enhancement of chemosensitivity of vorinostat.
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Report
(4 results)
Research Products
(6 results)
