The combination of epigenetic drugs SAHA and HCI-2509 synergistically inhibits EWS-FLI1 and tumor growth in Ewing sarcoma.

ABSTRACT:

Purpose

Epigenetic regulation is crucial in mammalian development and maintenance of tissue-cell specific functions. Perturbation of epigenetic balance may lead to alterations in gene expression, resulting in cellular transformation and malignancy. Previous studies in Ewing sarcoma (ES) have shown that the Nucleosome Remodeling Deacetylase (NuRD) complex binds directly to EWS-FLI1 oncoprotein and modulates its transcriptional activity. The role of EWS-FLI1 as a driver of proliferation and transformation in ES is widely known, but the effect of epigenetic drugs on fusion activity remains poorly described. The present study evaluated the combination effects of the histone deacetylases inhibitor suberoylanilide hydroxamic acid (SAHA) and Lysine-specific demethylase1 inhibitor (HCI-250

SUBMITTER: Garcia-Dominguez DJ 

PROVIDER: S-EPMC6101143 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature