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Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux
INTRODUCTION: Cholangiocarcinoma is characterized by aggressive tumor growth, high recurrence rates, and resistance against common chemotherapeutical regimes. The polyether-antibiotic Salinomycin is a promising drug in cancer therapy because of its ability to overcome apoptosis resistance of cancer...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790487/ https://www.ncbi.nlm.nih.gov/pubmed/29423070 http://dx.doi.org/10.18632/oncotarget.23339 |
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author | Klose, Johannes Guerlevik, Engin Trostel, Tina Kühnel, Florian Schmidt, Thomas Schneider, Martin Ulrich, Alexis |
author_facet | Klose, Johannes Guerlevik, Engin Trostel, Tina Kühnel, Florian Schmidt, Thomas Schneider, Martin Ulrich, Alexis |
author_sort | Klose, Johannes |
collection | PubMed |
description | INTRODUCTION: Cholangiocarcinoma is characterized by aggressive tumor growth, high recurrence rates, and resistance against common chemotherapeutical regimes. The polyether-antibiotic Salinomycin is a promising drug in cancer therapy because of its ability to overcome apoptosis resistance of cancer cells and its selectivity against cancer stem cells. Here, we investigated the effectiveness of Salinomycin against cholangiocarcinoma in vivo, and analyzed interference of Salinomycin with autophagic flux in human cholangiocarcinoma cells. RESULTS: Salinomycin reduces tumor cell viability, proliferation, migration, invasion, and induced apoptosis in vitro. Subcutaneous and intrahepatic cholangiocarcinoma growth in vivo was inhibited upon Salinomycin treatment. Analysis of autophagy reveals inhibition of autophagic activity. This was accompanied by accumulation of mitochondrial mass and increased generation of reactive oxygen species. CONCLUSIONS: This study demonstrates the effectiveness of Salinomycin against cholangiocarcinoma in vivo. Inhibition of autophagic flux represents an underlying molecular mechanism of Salinomycin against cholangiocarcinoma. METHODS: The two murine cholangiocarcinoma cell lines p246 and p254 were used to analyze tumor cell proliferation, viability, migration, invasion, and apoptosis in vitro. For in vivo studies, murine cholangiocarcinoma cells were injected into syngeneic C57-BL/6-mice to initiate subcutaneous cholangiocarcinoma growth. Intrahepatic tumor growth was induced by electroporation of oncogenic transposon-plasmids into the left liver lobe. For mechanistic studies in human cells, TFK-1 and EGI-1 were used, and activation of autophagy was analyzed after exposure to Salinomycin. |
format | Online Article Text |
id | pubmed-5790487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57904872018-02-08 Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux Klose, Johannes Guerlevik, Engin Trostel, Tina Kühnel, Florian Schmidt, Thomas Schneider, Martin Ulrich, Alexis Oncotarget Research Paper INTRODUCTION: Cholangiocarcinoma is characterized by aggressive tumor growth, high recurrence rates, and resistance against common chemotherapeutical regimes. The polyether-antibiotic Salinomycin is a promising drug in cancer therapy because of its ability to overcome apoptosis resistance of cancer cells and its selectivity against cancer stem cells. Here, we investigated the effectiveness of Salinomycin against cholangiocarcinoma in vivo, and analyzed interference of Salinomycin with autophagic flux in human cholangiocarcinoma cells. RESULTS: Salinomycin reduces tumor cell viability, proliferation, migration, invasion, and induced apoptosis in vitro. Subcutaneous and intrahepatic cholangiocarcinoma growth in vivo was inhibited upon Salinomycin treatment. Analysis of autophagy reveals inhibition of autophagic activity. This was accompanied by accumulation of mitochondrial mass and increased generation of reactive oxygen species. CONCLUSIONS: This study demonstrates the effectiveness of Salinomycin against cholangiocarcinoma in vivo. Inhibition of autophagic flux represents an underlying molecular mechanism of Salinomycin against cholangiocarcinoma. METHODS: The two murine cholangiocarcinoma cell lines p246 and p254 were used to analyze tumor cell proliferation, viability, migration, invasion, and apoptosis in vitro. For in vivo studies, murine cholangiocarcinoma cells were injected into syngeneic C57-BL/6-mice to initiate subcutaneous cholangiocarcinoma growth. Intrahepatic tumor growth was induced by electroporation of oncogenic transposon-plasmids into the left liver lobe. For mechanistic studies in human cells, TFK-1 and EGI-1 were used, and activation of autophagy was analyzed after exposure to Salinomycin. Impact Journals LLC 2017-12-16 /pmc/articles/PMC5790487/ /pubmed/29423070 http://dx.doi.org/10.18632/oncotarget.23339 Text en Copyright: © 2018 Klose et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Klose, Johannes Guerlevik, Engin Trostel, Tina Kühnel, Florian Schmidt, Thomas Schneider, Martin Ulrich, Alexis Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux |
title | Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux |
title_full | Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux |
title_fullStr | Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux |
title_full_unstemmed | Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux |
title_short | Salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux |
title_sort | salinomycin inhibits cholangiocarcinoma growth by inhibition of autophagic flux |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790487/ https://www.ncbi.nlm.nih.gov/pubmed/29423070 http://dx.doi.org/10.18632/oncotarget.23339 |
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