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High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor

We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yield...

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Autores principales: Zhang, Le, Yang, Zhaoying, Granieri, Letizia, Pasculescu, Adrian, Datti, Alessandro, Asa, Sylvia L., Xu, Zheli, Ezzat, Shereen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991430/
https://www.ncbi.nlm.nih.gov/pubmed/26942566
http://dx.doi.org/10.18632/oncotarget.7890
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author Zhang, Le
Yang, Zhaoying
Granieri, Letizia
Pasculescu, Adrian
Datti, Alessandro
Asa, Sylvia L.
Xu, Zheli
Ezzat, Shereen
author_facet Zhang, Le
Yang, Zhaoying
Granieri, Letizia
Pasculescu, Adrian
Datti, Alessandro
Asa, Sylvia L.
Xu, Zheli
Ezzat, Shereen
author_sort Zhang, Le
collection PubMed
description We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer.
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spelling pubmed-49914302016-09-01 High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor Zhang, Le Yang, Zhaoying Granieri, Letizia Pasculescu, Adrian Datti, Alessandro Asa, Sylvia L. Xu, Zheli Ezzat, Shereen Oncotarget Research Paper We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer. Impact Journals LLC 2016-03-03 /pmc/articles/PMC4991430/ /pubmed/26942566 http://dx.doi.org/10.18632/oncotarget.7890 Text en Copyright: © 2016 Zhang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Le
Yang, Zhaoying
Granieri, Letizia
Pasculescu, Adrian
Datti, Alessandro
Asa, Sylvia L.
Xu, Zheli
Ezzat, Shereen
High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor
title High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor
title_full High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor
title_fullStr High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor
title_full_unstemmed High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor
title_short High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor
title_sort high-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991430/
https://www.ncbi.nlm.nih.gov/pubmed/26942566
http://dx.doi.org/10.18632/oncotarget.7890
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