Proteome analyses of the growth inhibitory effects of NCH-51, a novel histone deacetylase inhibitor, on lymphoid malignant cells

Leukemia. 2007 Nov;21(11):2344-53. doi: 10.1038/sj.leu.2404902. Epub 2007 Aug 9.


Recent reports showing successful inhibition of cancer and leukemia cell growth using histone deacetylase inhibitor (HDACi) compounds have highlighted the potential use of HDACi as anti-cancer agents. However, high incidence of toxicity and low stability in vivo were observed with hydroxamic acid-based HDACi such as suberoylanilide hydroxamic acid (SAHA), thus limiting its clinical applicability. In this study, we found that a novel non-hydroxamate HDACi NCH-51 could inhibit the cell growth of a variety of lymphoid malignant cells through apoptosis induction, more effectively than SAHA. Activation of caspase-3, -8 and -9, but not -7 was detected after the treatment with NCH-51. Gene expression profiles showed that NCH-51 and SAHA similarly upregulated p21 and downregulated anti-apoptotic molecules including survivin, bcl-w and c-FLIP. Proteome analysis using two-dimensional electrophoresis revealed that NCH-51 upregulated anti-oxidant molecules including peroxiredoxin 1 and 2 and glutathione S-transferase at the protein level. Interestingly, NCH-51 induced reactive oxygen species (ROS) after 8 h whereas SAHA continuously declined ROS. Pretreatment with an antioxidant, N-acetyl-L-cysteine, abolished the cytotoxicity of NCH-51. These findings suggest that NCH-51 exhibits cytotoxicity by sustaining ROS at the higher level greater than SAHA. This study indicates the therapeutic efficacy of NCH-51 and novel insights for anti-HDAC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry
  • Apoptosis
  • Cell Cycle
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Histone Deacetylase Inhibitors*
  • Humans
  • Leukemia / drug therapy*
  • Lymphoma / drug therapy*
  • Peroxiredoxins
  • Proteome
  • Proteomics / methods*
  • Reactive Oxygen Species
  • Sulfhydryl Compounds / pharmacology*


  • Antioxidants
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • NCH-51 compound
  • Proteome
  • Reactive Oxygen Species
  • Sulfhydryl Compounds
  • Peroxiredoxins