Proteomic analysis of pancreatic endocrine tumor cell lines treated with the histone deacetylase inhibitor trichostatin A.
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.
Cecconi
Daniela
D
Department of Science and Technologies, Section of Biochemical Methodologies, University of Verona, Verona, Italy.
Donadelli
Massimo
M
Rinalducci
Sara
S
Zolla
Lello
L
Scupoli
Maria Teresa
MT
Scarpa
Aldo
A
Palmieri
Marta
M
Righetti
Pier Giorgio
PG
D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor / Q000187:drug effects*; D049109:Cell Proliferation; D016000:Cluster Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D004701:Endocrine Gland Neoplasms / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D013058:Mass Spectrometry; D010190:Pancreatic Neoplasms / Q000737:chemistry*; D020543:Proteome / Q000032:analysis*
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D020543:Proteome; C012589:trichostatin A