The possibility of HSP70 as a therapeutic target in combination with HDACi

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591626
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kagoshima University (2014); Okayama University (2012-2013)
• Principal Investigator: FUJII Kazuyasu 鹿児島大学, 医学部・歯学部附属病院, 講師 (70452571)
• Co-Investigator(Kenkyū-buntansha): KONDO Tadashi 独立行政法人国立がん研究センター, 希少がん研究分野, 分野長 (30284061)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: HDAC阻害剤 / HSP72

Outline of Final Research Achievements

Using proteomic analysis of lymphoid cell lines, we identified HSP72, an inducible isoform of HSP70 family, was increased in histone deacetylase inhibitor (HDACi)-resistant cell line group. However, the functional role of HSP72 on HDACi-resistance had been largely unknown. In this study, we first established HSP72 stably transfected Jurkat cells, and we identified that HDACi-induced apoptosis and caspase activities were decreased and that base line expression level of bcl-2 and XIAP were increased in HSP72 overexpressed cells. On the other hand, HSP72 knock down Hut78 cell line was more sensitive for HDACi compared to MOCK cell line. Finally, we identified quercetin, an inhibitor of HSP70, enhanced HDACi-induced suppression of cell proliferation and HDACi-induced apoptosis in Hut78 cells. In conclusion, HSP72 is a possible target for combination therapy of HDACi.

Free Research Field

皮膚科学