Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Mayr, C; Wagner, A; Loeffelberger, M; Bruckner, D; Jakab, M; Berr, F; Di Fazio, P; Ocker, M; Neureiter, D; Pichler, M; Kiesslich, T.
The BMI1 inhibitor PTC-209 is a potential compound to halt cellular growth in biliary tract cancer cells.
Oncotarget. 2016; 7(1):745-758
Doi: 10.18632/oncotarget.6378
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- Co-Autor*innen der Med Uni Graz
- Pichler Martin
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- Abstract:
- BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and is up-regulated in biliary tract cancer (BTC), contributing to aggressive clinical features. In this study we investigated the cytotoxic effects of PTC-209, a recently developed inhibitor of BMI1, in BTC cells. PTC-209 reduced overall viability in BTC cell lines in a dose-dependent fashion (0.04 - 20 µM). Treatment with PTC-209 led to slightly enhanced caspase activity and stop of cell proliferation. Cell cycle analysis revealed that PTC-209 caused cell cycle arrest at the G1/S checkpoint. A comprehensive investigation of expression changes of cell cycle-related genes showed that PTC-209 caused significant down-regulation of cell cycle-promoting genes as well as of genes that contribute to DNA synthesis initiation and DNA repair, respectively. This was accompanied by significantly elevated mRNA levels of cell cycle inhibitors. In addition, PTC-209 reduced sphere formation and, in a cell line-dependent manner, aldehyde dehydrogease-1 positive cells. We conclude that PTC-209 might be a promising drug for future in vitro and in vivo studies in BTC.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents - pharmacology
- Biliary Tract Neoplasms - genetics
- Biliary Tract Neoplasms - metabolism
- Biliary Tract Neoplasms - pathology
- Cell Line, Tumor -
- Cell Proliferation - drug effects
- Cell Proliferation - genetics
- Cell Survival - drug effects
- Cell Survival - genetics
- Cisplatin - pharmacology
- Dose-Response Relationship, Drug -
- Drug Synergism -
- Flow Cytometry -
- G1 Phase Cell Cycle Checkpoints - drug effects
- G1 Phase Cell Cycle Checkpoints - genetics
- Gene Expression Regulation, Neoplastic - drug effects
- Heterocyclic Compounds, 2-Ring - pharmacology
- Humans -
- Immunohistochemistry -
- Neoplastic Stem Cells - drug effects
- Neoplastic Stem Cells - metabolism
- Polycomb Repressive Complex 1 - antagonists & inhibitors
- Polycomb Repressive Complex 1 - genetics
- Polycomb Repressive Complex 1 - metabolism
- Reverse Transcriptase Polymerase Chain Reaction -
- Thiazoles - pharmacology
- Find related publications in this database (Keywords)
- biliary tract cancer
- PRC1
- PTC-209
- cell cycle arrest
- BMI1