Trichostatin A alters cytoskeleton and energy metabolism of pancreatic adenocarcinoma cells: An in depth proteomic study

Journal of Cellular Biochemistry
Elisa Dalla PozzaMassimo Donadelli

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal of all human cancers with a high mortality rate. Resistance to conventional treatments and chemotherapeutics is a typical feature of PDAC. To investigate the causes of drug resistance it is essential to deeply investigate the mechanism of action of chemotherapeutics. In this study, we performed an in depth shotgun proteomic approach using the label-free proteomic SWATH-MS analysis to investigate novel insights of the mechanism of action of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) in PDAC cells. This proteomic analysis in PaCa44 cells and data elaboration of TSA-regulated proteins by bioinformatics showed an overall up-regulation of cytokeratins and other proteins related to the cytoskeleton organization, keratinization, and apoptotic cell death. On the contrary, a large amount of the down-regulated proteins by TSA treatment belongs to the cellular energetic metabolism and to the machinery of protein synthesis, such as ribosomal proteins, determining synergistic cell growth inhibition by the combined treatment of TSA and the glycolytic inhibitor 2-deoxy-d-glucose in a panel of PDAC cell lines. Data are available via ProteomeXchange with identi...Continue Reading

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Citations

Sep 25, 2019·Cancers·Miguel Sánchez-ÁlvarezMarco Cordani
Aug 7, 2020·Expert Review of Proteomics·Paula MeleadyMartin Clynes
May 31, 2019·Scientific Reports·Daniela CecconiMaria Teresa Valenti
Dec 26, 2018·Oxidative Medicine and Cellular Longevity·Jiao LuoMengtao Zhou
Mar 12, 2021·Frontiers in Molecular Biosciences·Elettra BarberisMarcello Manfredi
Apr 3, 2021·Molecular Biology Reports·Shruti GuptaKiran Kumar Tejavath
May 1, 2021·International Journal of Molecular Sciences·Marco PedrazziMonica Averna
Aug 10, 2021·Frontiers in Microbiology·Paolo CostaRoberto Mazzoli

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