Cargando…

Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models

Anaplastic thyroid cancer (ATC) is a rare and lethal human malignancy with no known effective therapies in the majority of cases. Despite the use of conventional treatments such as chemotherapy, radiation and surgical resection, this disease remains almost universally fatal. In the present study, we...

Descripción completa

Detalles Bibliográficos
Autores principales: Pinto, Nicole, Prokopec, Stephenie D., Vizeacoumar, Frederick, Searle, Karlee, Lowerison, Matthew, Ruicci, Kara M., Yoo, John, Fung, Kevin, MacNeil, Danielle, Lacefield, Jim C., Leong, Hon S., Mymryk, Joe S., Barrett, John W., Datti, Alessandro, Boutros, Paul C., Nichols, Anthony C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231667/
https://www.ncbi.nlm.nih.gov/pubmed/30419054
http://dx.doi.org/10.1371/journal.pone.0207152
_version_ 1783370274848112640
author Pinto, Nicole
Prokopec, Stephenie D.
Vizeacoumar, Frederick
Searle, Karlee
Lowerison, Matthew
Ruicci, Kara M.
Yoo, John
Fung, Kevin
MacNeil, Danielle
Lacefield, Jim C.
Leong, Hon S.
Mymryk, Joe S.
Barrett, John W.
Datti, Alessandro
Boutros, Paul C.
Nichols, Anthony C.
author_facet Pinto, Nicole
Prokopec, Stephenie D.
Vizeacoumar, Frederick
Searle, Karlee
Lowerison, Matthew
Ruicci, Kara M.
Yoo, John
Fung, Kevin
MacNeil, Danielle
Lacefield, Jim C.
Leong, Hon S.
Mymryk, Joe S.
Barrett, John W.
Datti, Alessandro
Boutros, Paul C.
Nichols, Anthony C.
author_sort Pinto, Nicole
collection PubMed
description Anaplastic thyroid cancer (ATC) is a rare and lethal human malignancy with no known effective therapies in the majority of cases. Despite the use of conventional treatments such as chemotherapy, radiation and surgical resection, this disease remains almost universally fatal. In the present study, we identified the JAK2 inhibitor Lestaurtinib as a potent compound when testing against 13 ATC cell lines. Lestaurtinib demonstrated a potent antiproliferative effect in vitro at nanomolar concentrations. Furthermore, Lestaurtinib impeded cell migration and the ability to form colonies from single cells using scratch-wound and colony formation assays, respectively. Flow cytometry was used for cell cycle analysis following drug treatment and demonstrated arrest at the G2/M phase of the cell cycle, indicative of a cytostatic effect. In vivo studies using the chick chorioallantoic membrane xenograft models demonstrated that treatment with Lestaurtinib resulted in a significant decrease in endpoint tumor volume and vascularity using power Doppler ultrasound imaging. Overall, this study provides evidence that Lestaurtinib is a potent antiproliferative agent with potential antiangiogenic activity that warrants further investigation as a targeted therapy for ATC.
format Online
Article
Text
id pubmed-6231667
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-62316672018-11-19 Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models Pinto, Nicole Prokopec, Stephenie D. Vizeacoumar, Frederick Searle, Karlee Lowerison, Matthew Ruicci, Kara M. Yoo, John Fung, Kevin MacNeil, Danielle Lacefield, Jim C. Leong, Hon S. Mymryk, Joe S. Barrett, John W. Datti, Alessandro Boutros, Paul C. Nichols, Anthony C. PLoS One Research Article Anaplastic thyroid cancer (ATC) is a rare and lethal human malignancy with no known effective therapies in the majority of cases. Despite the use of conventional treatments such as chemotherapy, radiation and surgical resection, this disease remains almost universally fatal. In the present study, we identified the JAK2 inhibitor Lestaurtinib as a potent compound when testing against 13 ATC cell lines. Lestaurtinib demonstrated a potent antiproliferative effect in vitro at nanomolar concentrations. Furthermore, Lestaurtinib impeded cell migration and the ability to form colonies from single cells using scratch-wound and colony formation assays, respectively. Flow cytometry was used for cell cycle analysis following drug treatment and demonstrated arrest at the G2/M phase of the cell cycle, indicative of a cytostatic effect. In vivo studies using the chick chorioallantoic membrane xenograft models demonstrated that treatment with Lestaurtinib resulted in a significant decrease in endpoint tumor volume and vascularity using power Doppler ultrasound imaging. Overall, this study provides evidence that Lestaurtinib is a potent antiproliferative agent with potential antiangiogenic activity that warrants further investigation as a targeted therapy for ATC. Public Library of Science 2018-11-12 /pmc/articles/PMC6231667/ /pubmed/30419054 http://dx.doi.org/10.1371/journal.pone.0207152 Text en © 2018 Pinto et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pinto, Nicole
Prokopec, Stephenie D.
Vizeacoumar, Frederick
Searle, Karlee
Lowerison, Matthew
Ruicci, Kara M.
Yoo, John
Fung, Kevin
MacNeil, Danielle
Lacefield, Jim C.
Leong, Hon S.
Mymryk, Joe S.
Barrett, John W.
Datti, Alessandro
Boutros, Paul C.
Nichols, Anthony C.
Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models
title Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models
title_full Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models
title_fullStr Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models
title_full_unstemmed Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models
title_short Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models
title_sort lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231667/
https://www.ncbi.nlm.nih.gov/pubmed/30419054
http://dx.doi.org/10.1371/journal.pone.0207152
work_keys_str_mv AT pintonicole lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT prokopecstephenied lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT vizeacoumarfrederick lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT searlekarlee lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT lowerisonmatthew lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT ruiccikaram lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT yoojohn lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT fungkevin lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT macneildanielle lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT lacefieldjimc lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT leonghons lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT mymrykjoes lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT barrettjohnw lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT dattialessandro lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT boutrospaulc lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels
AT nicholsanthonyc lestaurtinibisapotentinhibitorofanaplasticthyroidcancercelllinemodels