Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance

In this in vitro study, we determined whether masitinib could reverse multidrug resistance (MDR) in cells overexpressing the ATP binding cassette subfamily G member 2 (ABCG2) transporter. Masitinib (1.25 and 2.5 μM) significantly decreases the resistance to mitoxantrone (MX), SN38 and doxorubicin in...

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Main Authors:	KATHAWALA, RISHIL J., CHEN, JUN-JIANG, ZHANG, YUN-KAI, WANG, YI-JUN, PATEL, ATISH, WANG, DE-SHEN, TALELE, TANAJI T., ASHBY, CHARLES R., CHEN, ZHE-SHENG
Format:	Online
Language:	English
Published:	D.A. Spandidos 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027943/

id	pubmed-4027943
recordtype	oai_dc
spelling	pubmed-40279432014-05-20 Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance KATHAWALA, RISHIL J. CHEN, JUN-JIANG ZHANG, YUN-KAI WANG, YI-JUN PATEL, ATISH WANG, DE-SHEN TALELE, TANAJI T. ASHBY, CHARLES R. CHEN, ZHE-SHENG Article In this in vitro study, we determined whether masitinib could reverse multidrug resistance (MDR) in cells overexpressing the ATP binding cassette subfamily G member 2 (ABCG2) transporter. Masitinib (1.25 and 2.5 μM) significantly decreases the resistance to mitoxantrone (MX), SN38 and doxorubicin in HEK293 and H460 cells overexpressing the ABCG2 transporter. In addition, masitinib (2.5 μM) significantly increased the intracellular accumulation of [3H]-MX, a substrate for ABCG2, by inhibiting the function of ABCG2 and significantly decreased the efflux of [3H]-MX. However, masitinib (2.5 μM) did not significantly alter the expression of the ABCG2 protein. In addition, a docking model suggested that masitinib binds within the transmembrane region of a homology-modeled human ABCG2 transporter. Overall, our in vitro findings suggest that masitinib reverses MDR to various anti-neoplastic drugs in HEK293 and H460 cells overexpressing ABCG2 by inhibiting their transport activity as opposed to altering their levels of expression. D.A. Spandidos 2014-03-13 /pmc/articles/PMC4027943/ /pubmed/24626598 http://dx.doi.org/10.3892/ijo.2014.2341 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	KATHAWALA, RISHIL J. CHEN, JUN-JIANG ZHANG, YUN-KAI WANG, YI-JUN PATEL, ATISH WANG, DE-SHEN TALELE, TANAJI T. ASHBY, CHARLES R. CHEN, ZHE-SHENG
spellingShingle	KATHAWALA, RISHIL J. CHEN, JUN-JIANG ZHANG, YUN-KAI WANG, YI-JUN PATEL, ATISH WANG, DE-SHEN TALELE, TANAJI T. ASHBY, CHARLES R. CHEN, ZHE-SHENG Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance
author_facet	KATHAWALA, RISHIL J. CHEN, JUN-JIANG ZHANG, YUN-KAI WANG, YI-JUN PATEL, ATISH WANG, DE-SHEN TALELE, TANAJI T. ASHBY, CHARLES R. CHEN, ZHE-SHENG
author_sort	KATHAWALA, RISHIL J.
title	Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance
title_short	Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance
title_full	Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance
title_fullStr	Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance
title_full_unstemmed	Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance
title_sort	masitinib antagonizes atp-binding cassette subfamily g member 2-mediated multidrug resistance
description	In this in vitro study, we determined whether masitinib could reverse multidrug resistance (MDR) in cells overexpressing the ATP binding cassette subfamily G member 2 (ABCG2) transporter. Masitinib (1.25 and 2.5 μM) significantly decreases the resistance to mitoxantrone (MX), SN38 and doxorubicin in HEK293 and H460 cells overexpressing the ABCG2 transporter. In addition, masitinib (2.5 μM) significantly increased the intracellular accumulation of [3H]-MX, a substrate for ABCG2, by inhibiting the function of ABCG2 and significantly decreased the efflux of [3H]-MX. However, masitinib (2.5 μM) did not significantly alter the expression of the ABCG2 protein. In addition, a docking model suggested that masitinib binds within the transmembrane region of a homology-modeled human ABCG2 transporter. Overall, our in vitro findings suggest that masitinib reverses MDR to various anti-neoplastic drugs in HEK293 and H460 cells overexpressing ABCG2 by inhibiting their transport activity as opposed to altering their levels of expression.
publisher	D.A. Spandidos
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027943/
_version_	1612091192200134656

Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance

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