Abstract
| Original language | English |
|---|---|
| Journal | Int. J. Mol. Sci. |
| Volume | 19 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 12 Oct 2018 |
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
-
SDG 3 Good Health and Well-being
Keywords
- Apoptosis
- Cytotoxicity
- Histone deacetylases
- LMK-235
- Pancreatic neuroendocrine tumors
- beta actin
- chromogranin
- citarinostat
- histone deacetylase
- histone deacetylase 5
- LMK 235
- somatostatin receptor 2
- unclassified drug
- HDAC4 protein, human
- HDAC5 protein, human
- histone
- histone deacetylase inhibitor
- repressor protein
- animal cell
- animal tissue
- antiproliferative activity
- apoptosis rate
- Article
- caspase assay
- cell culture
- cell viability
- cytotoxicity
- epigenetics
- immunocytochemistry
- immunofluorescence microscopy
- nonhuman
- pancreas islet cell tumor
- pharmacology
- protein expression
- resazurin assay
- Western blotting
- acetylation
- cell proliferation
- cell survival
- drug effect
- gene expression regulation
- human
- metabolism
- neuroendocrine tumor
- pancreas tumor
- tumor cell line
- Acetylation
- Cell Line, Tumor
- Cell Proliferation
- Cell Survival
- Gene Expression Regulation, Neoplastic
- Histone Deacetylase Inhibitors
- Histone Deacetylases
- Histones
- Humans
- Neuroendocrine Tumors
- Pancreatic Neoplasms
- Repressor Proteins
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In: Int. J. Mol. Sci., Vol. 19, No. 10, 12.10.2018.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells
AU - Wanek, J.
AU - Gaisberger, M.
AU - Beyreis, M.
AU - Mayr, C.
AU - Helm, K.
AU - Primavesi, F.
AU - Jäger, T.
AU - Di Fazio, P.
AU - Jakab, M.
AU - Wagner, A.
AU - Neureiter, D.
AU - Kiesslich, T.
N1 - Cited By :35 Export Date: 14 December 2023 Correspondence Address: Kiesslich, T.; Department of Internal Medicine I, Austria; email: [email protected] Chemicals/CAS: citarinostat, 1316215-12-9; histone deacetylase, 9076-57-7; histone, 9062-68-4; HDAC4 protein, human; HDAC5 protein, human; Histone Deacetylase Inhibitors; Histone Deacetylases; Histones; Repressor Proteins References: Schimmack, S., Svejda, B., Lawrence, B., Kidd, M., Modlin, I.M., The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors (2011) Langenbecks Arch. Surg., 396, pp. 273-298; Lawrence, B., Gustafsson, B.I., Chan, A., Svejda, B., Kidd, M., Modlin, I.M., The epidemiology of gastroenteropancreatic neuroendocrine tumors (2011) Endocrinol. Metab. Clin. N. Am., 40, pp. 1-18; Modlin, I.M., Oberg, K., Chung, D.C., Jensen, R.T., de Herder, W.W., Thakker, R.V., Caplin, M., Krenning, E.P., Gastroenteropancreatic neuroendocrine tumours (2008) Lancet Oncol, 9, pp. 61-72; Bosman, F.T., Carneiro, F., Hruban, R.H., Theise, N.D., Nomenclature and classification of neuroendocrine neoplasms of the digestive system (2010) WHO Classification of Tumours of the Digestive System, pp. 13-14. , 4th ed.; WHO Press World Health Organization: Geneva, Switzerland, ISBN 9789283224327; Öberg, K., Knigge, U., Kwekkeboom, D., Perren, A., Neuroendocrine gastro-entero-pancreatic tumors: Esmo clinical practice guidelines for diagnosis, treatment and follow-up (2012) Ann. Oncol., 23, pp. 124-130; Berardi, R., Rinaldi, S., Torniai, M., Morgese, F., Partelli, S., Caramanti, M., Onofri, A., Falconi, M., Gastrointestinal neuroendocrine tumors: Searching the optimal treatment strategy—A literature review (2016) Crit. Rev. Oncol. 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PY - 2018/10/12
Y1 - 2018/10/12
N2 - 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. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
AB - 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. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
KW - Apoptosis
KW - Cytotoxicity
KW - Histone deacetylases
KW - LMK-235
KW - Pancreatic neuroendocrine tumors
KW - beta actin
KW - chromogranin
KW - citarinostat
KW - histone deacetylase
KW - histone deacetylase 5
KW - LMK 235
KW - somatostatin receptor 2
KW - unclassified drug
KW - HDAC4 protein, human
KW - HDAC5 protein, human
KW - histone
KW - histone deacetylase inhibitor
KW - repressor protein
KW - animal cell
KW - animal tissue
KW - antiproliferative activity
KW - apoptosis rate
KW - Article
KW - caspase assay
KW - cell culture
KW - cell viability
KW - cytotoxicity
KW - epigenetics
KW - immunocytochemistry
KW - immunofluorescence microscopy
KW - nonhuman
KW - pancreas islet cell tumor
KW - pharmacology
KW - protein expression
KW - resazurin assay
KW - Western blotting
KW - acetylation
KW - cell proliferation
KW - cell survival
KW - drug effect
KW - gene expression regulation
KW - human
KW - metabolism
KW - neuroendocrine tumor
KW - pancreas tumor
KW - tumor cell line
KW - Acetylation
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Cell Survival
KW - Gene Expression Regulation, Neoplastic
KW - Histone Deacetylase Inhibitors
KW - Histone Deacetylases
KW - Histones
KW - Humans
KW - Neuroendocrine Tumors
KW - Pancreatic Neoplasms
KW - Repressor Proteins
U2 - 10.3390/ijms19103128
DO - 10.3390/ijms19103128
M3 - Article
SN - 1661-6596
VL - 19
JO - Int. J. Mol. Sci.
JF - Int. J. Mol. Sci.
IS - 10
ER -