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Forschungsdatenbank PMU-SQQUID

Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells.
Wanek, J; Gaisberger, M; Beyreis, M; Mayr, C; Helm, K; Primavesi, F; Jäger, T; Di Fazio, P; Jakab, M; Wagner, A; Neureiter, D; Kiesslich, T;
Int J Mol Sci. 2018; 19(10):
Originalarbeiten (Zeitschrift)


Beyreis Marlena
Gaisberger Martin
Helm Katharina
Jäger Tarkan
Jakab Martin
Kiesslich Tobias
Mayr Christian Reinhard
Neureiter Daniel
Wagner Andrej


Histone deacetylases (HDACs) play a key role in epigenetic mechanisms in health and disease and their dysfunction is implied in several cancer entities. Analysis of expression patterns in pancreatic neuroendocrine tumors (pNETs) indicated HDAC5 to be a potential target for future therapies. As a first step towards a possible treatment, the aim of this study was to evaluate the in vitro cellular and molecular effects of HDAC5 inhibition in pNET cells. Two pNET cell lines, BON-1 and QGP-1, were incubated with different concentrations of the selective class IIA HDAC inhibitor, LMK-235. Effects on cell viability were determined using the resazurin-assay, the caspase-assay, and Annexin-V staining. Western Blot and immunofluorescence microscopy were performed to assess the effects on HDAC5 functionality. LMK-235 lowered overall cell viability by inducing apoptosis in a dose- and time-dependent manner. Furthermore, acetylation of histone-H3 increased with higher LMK-235 concentrations, indicating functional inhibition of HDAC4/5. Immunocytochemical analysis showed that proliferative activity (phosphohistone H3 and Ki-67) decreased at highest concentrations of LMK-235 while chromogranin and somatostatin receptor 2 (SSTR2) expression increased in a dose-dependent manner. HDAC5 expression was found to be largely unaffected by LMK-235. These findings indicate LMK-235 to be a potential therapeutic approach for the development of an effective and selective pNET treatment.

Find related publications in this database (Keywords)

pancreatic neuroendocrine tumors
histone deacetylases