A proteomic approach for evaluating the cell response to a novel histone deacetylase inhibitor in colon cancer cells.
Epigenetic inactivation of gene expression is a general phenomenon associated with malignant transformation. Recently, we have found that a novel series of histone deacetylases (HDAC) inhibitors exhibit a broad-spectrum inhibition profile characterized by a marked effect on acetylation of histone and non-histone proteins. RC307, a representative compound of this series, caused a growth-inhibitory effect in colon carcinoma cells HCT116 associated with G2 accumulation and induction of apoptosis. The present study was designed to investigate the effect of RC307 on protein expressions in the HCT116 cells following treatment with cytotoxic drug concentrations. HCT116 cells were cultured in the absence or presence of RC307 and total cell lysates, as well as nuclear proteins, were extracted. The protein samples were then subjected to two-dimensional polyacrylamide gel electrophoresis, and the 2D gel images were compared to discover the protein changes caused by RC307 treatment. A total of 48 and 46 different spots were found to be modulated by RC307 in total lysates and nuclear proteome of HCT116 cell line. The modulated proteins were identified by tandem mass spectrometry. We found that RC307 exposure modulates proteins that are involved in proliferation, cell cycle regulation, apoptosis, gene expression, as well as chromatin and cytoskeleton organization.
Milli
Alberto
A
Dipartimento Scientifico e Tecnologico, Laboratorio di Proteomica, Università degli Studi di Verona, Verona, Italy.
Cecconi
Daniela
D
Campostrini
Natascia
N
Timperio
Anna Maria
AM
Zolla
Lello
L
Righetti
Sabina Carla
SC
Zunino
Franco
F
Perego
Paola
P
Benedetti
Valentina
V
Gatti
Laura
L
Odreman
Federico
F
Vindigni
Alessandro
A
Righetti
Pier Giorgio
PG
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004353:Drug Evaluation, Preclinical; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D040901:Proteomics / Q000379:methods*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors