Novel small-molecule SIRT1 inhibitors induce cell death in leukaemia cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591413
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Fukuoka University
• Principal Investigator: KOZAKO Tomohiro 福岡大学, 薬学部, 准教授 (40398300)
• Co-Investigator(Renkei-kenkyūsha): SUZUKI Takayoshi 京都府立医科大学, 医学部, 教授 (90372838)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ATL / HTLV-1 / SIRT1

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.

Free Research Field

血液腫瘍学