The effects of the histone-deacetylases inhibitor trichostatin A (TSA) on the growth of three different human pancreatic endocrine carcinoma cell lines (CM, BON and QGP-1), has been assessed via dosage-dependent growth inhibition curves. All cell lines showed strong inhibition of cell growth after TSA with similar IC50 values: 80.5 nM (CM), 61.6 nM (BON) and 86 nM (QGP-1). TSA treatment determined both cell cycle arrest in G2/M phase and apoptotis. 2D-PAGE analysis revealed 30, 39 and 29 different proteins differentially expressed after TSA treatment in the CM, BON and QGP-1 cell lines, respectively. The most important groups of modulated proteins, identified by nano RP-HPLC-ESI-MS/MS, belong to cell proliferation, cell cycle and apoptosis class (such as peroxiredoxins 1 and 2, the Diablo protein, HSP27). Other proteins belong to processes such as regulation of gene expression (nucleophosmin, oncoprotein-Dek), signal transduction (calcium-calmodulin), chromatin and cytoscheleton organization (calgizzarin, dynein, lamin), RNA splicing (nucleolin, HNRPC), and protein folding (HSP70). The present data are in agreement with previous proteomic analyses performed on pancreatic ductal carcinoma cell lines [Cecconi, D., et al., Electrophoresis 2003; Cecconi, D., et al., J Proteome Res. 2005] and place histone-deacetylases inhibitors among the potentially most powerful drugs for treatment of pancreatic tumours.
Pancreatic endocrine tumours, a proteomic investigation of the trichostatin-A antitumoral effect
CECCONI, Daniela;DONADELLI, Massimo;SCARPA, Aldo;PALMIERI, Marta;BOSSI, Alessandra Maria;RIGHETTI, Piergiorgio
2006-01-01
Abstract
The effects of the histone-deacetylases inhibitor trichostatin A (TSA) on the growth of three different human pancreatic endocrine carcinoma cell lines (CM, BON and QGP-1), has been assessed via dosage-dependent growth inhibition curves. All cell lines showed strong inhibition of cell growth after TSA with similar IC50 values: 80.5 nM (CM), 61.6 nM (BON) and 86 nM (QGP-1). TSA treatment determined both cell cycle arrest in G2/M phase and apoptotis. 2D-PAGE analysis revealed 30, 39 and 29 different proteins differentially expressed after TSA treatment in the CM, BON and QGP-1 cell lines, respectively. The most important groups of modulated proteins, identified by nano RP-HPLC-ESI-MS/MS, belong to cell proliferation, cell cycle and apoptosis class (such as peroxiredoxins 1 and 2, the Diablo protein, HSP27). Other proteins belong to processes such as regulation of gene expression (nucleophosmin, oncoprotein-Dek), signal transduction (calcium-calmodulin), chromatin and cytoscheleton organization (calgizzarin, dynein, lamin), RNA splicing (nucleolin, HNRPC), and protein folding (HSP70). The present data are in agreement with previous proteomic analyses performed on pancreatic ductal carcinoma cell lines [Cecconi, D., et al., Electrophoresis 2003; Cecconi, D., et al., J Proteome Res. 2005] and place histone-deacetylases inhibitors among the potentially most powerful drugs for treatment of pancreatic tumours.
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