Proteomic profiling of human colon cancer cells treated with the histone deacetylase inhibitor belinostat.
The anticancer drug belinostat is a hydroxamate histone deacetylase inhibitor that has shown significant antitumour activity in various tumour models and also in clinical trials. In this study, we utilized a proteomic approach in order to evaluate the effect of this drug on protein expression in the human colon cancer cell line HCT116. Protein extracts from untreated HCT116 cells, and cells grown for 24 h in the presence of 1 and 10 muM belinostat were analysed by 2-D gel electrophoresis. Proteins were visualized by colloidal Coomassie blue staining and quantitative analysis of gel images revealed 45 unique differentially expressed proteins that were identified by LC-MSMS analysis. Among these proteins, of particular interest are the downregulated proteins nucleophosmin and stratifin, and the upregulated proteins nucleolin, gelsolin, heterogeneous nuclear ribonucleoprotein K, annexin 1, and HSP90B that all were related to the proto-oncogene proteins p53, Myc, activator protein 1, and c-fos protein. The modulation of these proteins is consistent with the observations that belinostat is able to inhibit clonogenic cell growth of HCT116 cells and the biological role of these proteins will be discussed.
Beck
Hans Christian
HC
Danish Technological Institute, Kolding, Denmark. hcb@teknologisk.dk
Petersen
Jørgen
J
Nielsen
Søren Jensby
SJ
Morsczeck
Christian
C
Morszeck
Christian
C
Jensen
Peter B
PB
Sehested
Maxwell
M
Grauslund
Morten
M
D015153:Blotting, Western; D016923:Cell Death; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003114:Colony-Forming Units Assay / Q000379:methods; D019295:Computational Biology; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D020869:Gene Expression Profiling; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D020543:Proteome / Q000737:chemistry*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000187:drug effects; D013449:Sulfonamides
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C000715470:MAS1 protein, human; D020543:Proteome; D000090063:Proto-Oncogene Mas; D013449:Sulfonamides; D006655:Histone Deacetylases; C487081:belinostat