A novel histone deacetylase inhibitor Chidamide induces G0/G1 arrest and apoptosis in myelodysplastic syndromes

Biomed Pharmacother. 2016 Oct:83:1032-1037. doi: 10.1016/j.biopha.2016.08.023. Epub 2016 Aug 16.

Abstract

Chidamide as a newly designed and synthesized histone deacetylase inhibitor induces an antitumor effect in various cancer, and it has been used in several clinical trials such as peripheral T cell lymphoma (PTCL). Here we demonstrate that Chidamide was able to increase the acetylation levels of histone H3 and decrease HDAC activity in MDS cell lines(SKM-1,MUTZ-1)and AML cell line(KG-1). In vitro, at low concentration (<250nM) of Chidamide inhibited cell proliferation and delayed G0/G1 cell cycle progression by down-regulating CDK2 and regulating p-P53 and P21 protein expression. Meanwhile,it also induced cell apoptosis by down-regulating Bcl-2 and up-regulating cleaved Caspase-3 and Bax protein expression.The results of the present study demonstrates the potential utility of Chidamide for the treatment of Myelodysplastic syndromes.

Keywords: Apoptosis; Cell cycle; Chidamide; HDAC inhibitor; Myelodysplastic syndrome.

MeSH terms

  • Acetylation / drug effects
  • Aminopyridines / pharmacology*
  • Apoptosis / drug effects*
  • Benzamides / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histones / metabolism
  • Humans
  • Myelodysplastic Syndromes / pathology*
  • Resting Phase, Cell Cycle / drug effects*

Substances

  • Aminopyridines
  • Benzamides
  • Histone Deacetylase Inhibitors
  • Histones
  • N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide