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Proteomic profiling of human colon cancer cells treated with the histone deacetylase inhibitor belinostat
Authors:Jørgen Petersen  Søren Jensby Nielsen  Christian Morszeck  Peter B Jensen  Maxwell Sehested  Morten Grauslund
Institution:1. Danish Technological Institute, Kolding, Denmark;2. Experimental Pathology Unit, Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark;3. TopoTarget A/S, Symbion Science Park, Copenhagen, Denmark;4. University of Regensburg, Department of Operative Dentistry and Periodontology, Regensburg, Germany;5. Laboratory for Experimental Medical Oncology, Finsen Center, Copenhagen University Hospital, Copenhagen, Denmark
Abstract: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 μM 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.
Keywords:2‐D PAGE  Belinostat  Cancer treatment  HCT116  Histone deacetylase inhibitor
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