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Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors

Microtubule-targeting agents are widely used as clinical drugs in the treatment of cancer. However, some kinase inhibitors can also disrupt microtubule organization by directly binding to tubulin. These unexpected effects may result in a plethora of harmful events and/or a misinterpretation of the e...

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Detalles Bibliográficos
Autor principal: Tanabe, Kenji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751111/
https://www.ncbi.nlm.nih.gov/pubmed/29168788
http://dx.doi.org/10.3390/ijms18122508
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author Tanabe, Kenji
author_facet Tanabe, Kenji
author_sort Tanabe, Kenji
collection PubMed
description Microtubule-targeting agents are widely used as clinical drugs in the treatment of cancer. However, some kinase inhibitors can also disrupt microtubule organization by directly binding to tubulin. These unexpected effects may result in a plethora of harmful events and/or a misinterpretation of the experimental results. Thus, further studies are needed to understand these dual inhibitors. In this review, I discuss the roles of dual inhibitors of kinase activity and microtubule function as well as describe the properties underlining their dual roles. Since both kinase and microtubule inhibitors cause cell toxicity and cell cycle arrest, it is difficult to determine which inhibitor is responsible for each phenotype. A discrimination of cell cycle arrest at G0/G1 or G2/M and/or image analyses of cellular phenotype may eventually lead to new insights on drug duality. Because of the indispensable roles of microtubules in mitosis and vesicle transport, I propose a simple and easy method to identify microtubule depolymerizing compounds.
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spelling pubmed-57511112018-01-08 Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors Tanabe, Kenji Int J Mol Sci Review Microtubule-targeting agents are widely used as clinical drugs in the treatment of cancer. However, some kinase inhibitors can also disrupt microtubule organization by directly binding to tubulin. These unexpected effects may result in a plethora of harmful events and/or a misinterpretation of the experimental results. Thus, further studies are needed to understand these dual inhibitors. In this review, I discuss the roles of dual inhibitors of kinase activity and microtubule function as well as describe the properties underlining their dual roles. Since both kinase and microtubule inhibitors cause cell toxicity and cell cycle arrest, it is difficult to determine which inhibitor is responsible for each phenotype. A discrimination of cell cycle arrest at G0/G1 or G2/M and/or image analyses of cellular phenotype may eventually lead to new insights on drug duality. Because of the indispensable roles of microtubules in mitosis and vesicle transport, I propose a simple and easy method to identify microtubule depolymerizing compounds. MDPI 2017-11-23 /pmc/articles/PMC5751111/ /pubmed/29168788 http://dx.doi.org/10.3390/ijms18122508 Text en © 2017 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Tanabe, Kenji
Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors
title Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors
title_full Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors
title_fullStr Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors
title_full_unstemmed Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors
title_short Microtubule Depolymerization by Kinase Inhibitors: Unexpected Findings of Dual Inhibitors
title_sort microtubule depolymerization by kinase inhibitors: unexpected findings of dual inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751111/
https://www.ncbi.nlm.nih.gov/pubmed/29168788
http://dx.doi.org/10.3390/ijms18122508
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