Nicotinamide potentiates HDAC inhibitor-induced cytotoxicity in human breast cancer cells through DNA damage accumulation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591923
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kyushu University
• Principal Investigator: UEHARA NORIHISA 九州大学, 歯学研究科(研究院), 助教 (30368211)
• 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)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: HDAC inhibitor / ニコチンアミド / 合成致死 / DNA損傷 / breast cancer

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.

Free Research Field

腫瘍細胞生物学