Sirtuin inhibitors, EX527 and AGK2, suppress cell migration by inhibiting HSF1 protein stability

被引：22

作者：

Kim, Hyun-Woo ^{[1
]}

Kim, Soo-A ^{[2
]}

Ahn, Sang-Gun ^{[1
]}

机构：

[1] Chosun Univ, Sch Dent, Dept Pathol, Kwangju 501759, South Korea

[2] Dongguk Univ, Dept Biochem, Coll Oriental Med, Gyeongju 780714, South Korea

来源：

ONCOLOGY REPORTS | 2016年 / 35卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Sirt1; Sirt2; HSF1; HSP27; EX527; AGK2; migration; OXIDATIVE STRESS; TRANSCRIPTION; DEACETYLASE; ACETYLATION; PROGRESSION; SURVIVAL; FACTOR-1; TARGETS; P53;

D O I：

10.3892/or.2015.4381

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The histone deacetylases (HDACs), Sirtuin 1 (Sirt1) and Sirt2, play crucial roles in many biological processes, including cell proliferation, differentiation and apoptosis. HDAC inhibitors have been considered as a potential therapeutic approach for various types of cancers. Here, we demonstrated that the Sirt1 and Sirt2 inhibitors EX527 and AGK2 suppressed cell growth and caused G1 phase arrest by inhibiting the expression of Cdk6 and/or Cdk4. An agar colony formation assay revealed that EX527 and AGK2 decreased colony formation in soft agar. Furthermore, EX527 and AGK2 pretreatment inhibited the expression of HSF1 and HSP27 and induced HSF1 ubiquitination. Sirt1 overexpression increased HSF1 expression and/or stabilization and induced cell migration in a scratch assay. Overall, these results indicate that EX527 and AGK2 suppress cell growth and migration by inhibiting HSF1 protein stability.

引用

页码：235 / 242

页数：8

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