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) have been assessed via dosage-dependent growth inhibition curves.
TSA determined strong inhibition of cell growth with similar IC(50) values for the different cell lines: 80.5 nM (CM), 61.6 nM (BON), and 86 nM (QGP-1), by arresting the cell cycle in G2/M phase and inducing apoptosis. 2DE and nano-RP-HPLC-ESI-MS/MS analysis revealed 34, 33, and 38 unique
proteins differentially expressed after
TSA treatment in the CM, BON, and QGP-1 cell lines, respectively. The most important groups of modulated
proteins belong to cell proliferation, cell cycle, and apoptosis classes (such as
peroxiredoxins 1 and 2, the diablo
protein, and HSP27). Other
proteins pertain to processes such as regulation of gene expression (
nucleophosmin,
oncoprotein dek), signal transduction (
calcium-
calmodulin),
chromatin, and cytoskeleton organization (calgizzarin,
dynein, and
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 the treatment of pancreatic
tumors.