Christian Mayr1, Andrej Wagner2, Angelika Stoecklinger3, Martin Jakab4, Romana Illig5, Frieder Berr6, Martin Pichler7, Pietro Di Fazio8, Matthias Ocker9, Daniel Neureiter5, Tobias Kiesslich10. 1. Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria Laboratory for Tumour Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria. 2. Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria. 3. Department of Molecular Biology, University of Salzburg, Salzburg, Austria. 4. Laboratory for Functional and Molecular Membrane Physiology, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria. 5. Institute of Pathology, Paracelsus Medical University, Salzburg, Austria. 6. Laboratory for Tumour Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria. 7. Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. 8. Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Marburg, Germany. 9. Institute for Surgical Research, Philipps University of Marburg, Marburg, Germany. 10. Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria Laboratory for Tumour Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria t.kiesslich@salk.at.
Abstract
BACKGROUND/AIM: Polycomb repressive complex 2 (PRC2), an epigenetic master regulator, contributes to progression and development of biliary tract cancer (BTC). The present study investigated the effects of the PRC2 inhibitor 3-deazaneplanocin A (DZNep) on BTC cell lines. MATERIALS AND METHODS: In vitro effects of DZNep treatment were analyzed for cell viability, gene expression and functional characteristics of cancer stem cell (CSC). RESULTS: DZNep treatment caused a cell line- and dose-dependent decrease in viability. In the EGI-1 cell line, a direct cytotoxic effect was accompanied by mRNA down-regulation of the PRC2 core components, cyclins as well as of CSC-related genes. Furthermore, DZNep affected putative CSCs by reduction of sphere formation and aldehyde dehydrogenase-1-positive cells. The stem cell characteristics of these subpopulations were verified by real-time polymerase chain reaction analysis. CONCLUSION: Taken together, our results show that DZNep might be a promising pharmacological agent for future therapies regarding BTC. Copyright
BACKGROUND/AIM: Polycomb repressive complex 2 (PRC2), an epigenetic master regulator, contributes to progression and development of biliary tract cancer (BTC). The present study investigated the effects of the PRC2 inhibitor 3-deazaneplanocin A (DZNep) on BTC cell lines. MATERIALS AND METHODS: In vitro effects of DZNep treatment were analyzed for cell viability, gene expression and functional characteristics of cancer stem cell (CSC). RESULTS:DZNep treatment caused a cell line- and dose-dependent decrease in viability. In the EGI-1 cell line, a direct cytotoxic effect was accompanied by mRNA down-regulation of the PRC2 core components, cyclins as well as of CSC-related genes. Furthermore, DZNep affected putative CSCs by reduction of sphere formation and aldehyde dehydrogenase-1-positive cells. The stem cell characteristics of these subpopulations were verified by real-time polymerase chain reaction analysis. CONCLUSION: Taken together, our results show that DZNep might be a promising pharmacological agent for future therapies regarding BTC. Copyright
Authors: Christian Mayr; Andrej Wagner; Magdalena Loeffelberger; Daniela Bruckner; Martin Jakab; Frieder Berr; Pietro Di Fazio; Matthias Ocker; Daniel Neureiter; Martin Pichler; Tobias Kiesslich Journal: Oncotarget Date: 2016-01-05
Authors: Christian Mayr; Matthias Ocker; Markus Ritter; Martin Pichler; Daniel Neureiter; Tobias Kiesslich Journal: World J Gastroenterol Date: 2017-04-14 Impact factor: 5.742
Authors: Christian Mayr; Marlena Beyreis; Andrej Wagner; Martin Pichler; Daniel Neureiter; Tobias Kiesslich Journal: Biomed Res Int Date: 2016-11-09 Impact factor: 3.411
Authors: Romana Urbas; Christian Mayr; Eckhard Klieser; Julia Fuereder; Doris Bach; Stefan Stättner; Florian Primavesi; Tarkan Jaeger; Stefanie Stanzer; Anna Lena Ress; Magdalena Löffelberger; Andrej Wagner; Frieder Berr; Markus Ritter; Martin Pichler; Daniel Neureiter; Tobias Kiesslich Journal: Int J Mol Sci Date: 2016-12-07 Impact factor: 5.923
Authors: Dino Bekric; Daniel Neureiter; Markus Ritter; Martin Jakab; Martin Gaisberger; Martin Pichler; Tobias Kiesslich; Christian Mayr Journal: J Clin Med Date: 2020-04-22 Impact factor: 4.241