Synergistic effect of trichostatin A and 5-aza-2'-deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: a proteomic study.
Our research group recently reported that pancreatic endocrine cancer cell lines are sensitive to the HDAC inhibitor trichostatin A (TSA). In the present paper, we show that the combined treatment of pancreatic endocrine tumour cell lines with TSA and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (DAC) determines a strong synergistic inhibition of proliferation mainly due to apoptotic cell death. Proteomic analysis demonstrates that the modulation of specific proteins correlates with the antiproliferative effect of the drugs. A schematic network clarifies the most important targets or pathways involved in pancreatic endocrine cancer growth inhibition by single or combined drug treatments, which include proteasome, mitochondrial apoptotic pathway and caspase related proteins, p53 and Ras related proteins. A comparison between the patterns of proteins regulated by TSA or DAC in endocrine and ductal pancreatic cancer cell lines is also presented.
Cecconi
Daniela
D
Dipartimento di Biotecnologie, Laboratorio di Proteomica, Università di Verona, Verona, Italy.
Donadelli
Massimo
M
Dalla Pozza
Elisa
E
Rinalducci
Sara
S
Zolla
Lello
L
Scupoli
Maria Teresa
MT
Righetti
Pier Giorgio
PG
Scarpa
Aldo
A
Palmieri
Marta
M
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000077209:Decitabine; D004357:Drug Synergism; D004701:Endocrine Gland Neoplasms / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine