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Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance.
- Source :
-
International journal of oncology [Int J Oncol] 2014 May; Vol. 44 (5), pp. 1634-42. Date of Electronic Publication: 2014 Mar 13. - Publication Year :
- 2014
-
Abstract
- 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 [(3)H]-MX, a substrate for ABCG2, by inhibiting the function of ABCG2 and significantly decreased the efflux of [(3)H]-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.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily G, Member 2
Antineoplastic Agents adverse effects
Benzamides
Cell Line, Tumor
Drug Resistance, Multiple genetics
Drug Synergism
HEK293 Cells
Humans
Mitoxantrone adverse effects
Models, Molecular
Molecular Docking Simulation
Piperidines
Pyridines
ATP-Binding Cassette Transporters antagonists & inhibitors
Drug Resistance, Multiple drug effects
Neoplasm Proteins antagonists & inhibitors
Protein Kinase Inhibitors pharmacology
Thiazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 44
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 24626598
- Full Text :
- https://doi.org/10.3892/ijo.2014.2341