Synergistic effect of trichostatin A and 5‐aza‐2′‐deoxycytidine on growth inhibition of pancreatic endocrine tumour cell lines: A proteomic study |
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| Authors: | Daniela Cecconi Massimo Donadelli Elisa Dalla Pozza Sara Rinalducci Lello Zolla Maria Teresa Scupoli Pier Giorgio Righetti Aldo Scarpa Marta Palmieri Dr. |
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| Affiliation: | 1. Dipartimento di Biotecnologie, Laboratorio di Proteomica, Università di Verona, Verona, Italy;2. Both authors contributed equally to this work and share the first authorship.;3. Dipartimento di Scienze Morfologico‐Biomediche, Sezione di Chimica Biologica, Università di Verona, Verona, Italy;4. Dipartimento di Scienze Ambientali, Università della Tuscia, Viterbo, Italy;5. Laboratorio Interdipartimentale di Ricerca Medica (LURM), Università di Verona, Verona, Italy;6. Dipartimento di Chimica, Ingegneria Chimica e dei Materiali “Giulio Natta”, Milano, Politecnico di Milano, Italy;7. Dipartimento di Patologia, Sezione di Anatomia Patologica, Università di Verona, Verona, Italy |
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| Abstract: | 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. |
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| Keywords: | DNA methyl transferase inhibitor Epigenetics Histone deacetylase inhibitor Pancreatic endocrine tumour |
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