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ABCG2 impairs the activity of the aurora kinase inhibitor tozasertib but not of alisertib.

Michaelis, Martin, Selt, Florian, Rothweiler, Florian, Wiese, Michael, Cinatl, Jindrich (2015) ABCG2 impairs the activity of the aurora kinase inhibitor tozasertib but not of alisertib. BMC research notes, 8 . p. 484. ISSN 1756-0500. (doi:10.1186/s13104-015-1405-4) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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http://www.biomedcentral.com/1756-0500/8/484

Abstract

BACKGROUND Recently, we have shown that the ATP-binding cassette (ABC) transporter ABCB1 interferes with the anti-cancer activity of the pan-aurora kinase inhibitor tozasertib (VX680, MK-0457) but not of the aurora kinase A and B inhibitor alisertib (MLN8237). Preliminary data had suggested tozasertib also to be a substrate of the ABC transporter ABCG2, another ABC transporter potentially involved in cancer cell drug resistance. Here, we studied the effect of ABCG2 on the activity of tozasertib and alisertib. RESULTS The tozasertib concentration that reduces cell viability by 50 % (IC50) was dramatically increased in ABCG2-transduced UKF-NB-3(ABCG2) cells (48.8-fold) compared to UKF-NB-3 cells and vector-transduced control cells. The ABCG2 inhibitor WK-X-34 reduced tozasertib IC50 to the level of non-ABCG2-expressing UKF-NB-3 cells. Furthermore, ABCG2 depletion from UKF-NB-3(ABCG2) cells using another lentiviral vector expressing an shRNA against the bicistronic mRNA of ABCG2 and eGFP largely re-sensitised these cells to tozasertib. In contrast, alisertib activity was not affected by ABCG2 expression. CONCLUSIONS Tozasertib but not alisertib activity is affected by ABCG2 expression. This should be considered within the design and analysis of experiments and clinical trials investigating these compounds.

Item Type: Article
DOI/Identification number: 10.1186/s13104-015-1405-4
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 30 Sep 2015 16:32 UTC
Last Modified: 29 May 2019 16:04 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/50700 (The current URI for this page, for reference purposes)
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