PARP inhibitors as P-glyoprotein substrates
Article
Lawlor, D., Martin, P., Busschots, S., Thery, J., O'Leary, J.J., Hennessy, B.T. and Stordal, B. 2014. PARP inhibitors as P-glyoprotein substrates. Journal of Pharmaceutical Sciences. 103 (6), pp. 1913-1920. https://doi.org/10.1002/jps.23952
Type | Article |
---|---|
Title | PARP inhibitors as P-glyoprotein substrates |
Authors | Lawlor, D., Martin, P., Busschots, S., Thery, J., O'Leary, J.J., Hennessy, B.T. and Stordal, B. |
Abstract | The cytotoxicity of PARP inhibitors olaparib, veliparib, and CEP-8983 were investigated in two P-glycoprotein (P-gp) overexpressing drug-resistant cell models (IGROVCDDP and KB-8-5-11). IGROVCDDP and KB-8-5-11 were both resistant to olaparib and resistance was reversible with the P-gp inhibitors elacridar, zosuquidar, and valspodar. In contrast, the P-gp overexpressing models were not resistant to veliparib or CEP-8983. Olaparib and veliparib did not induce protein expression of P-gp in IGROVCDDP or KB-8-5-11 at doses that successfully inhibit PARP. Olaparib therefore appears to be a P-gp substrate. Veliparib and CEP-8983 do not appear to be substrates. Veliparib and CEP-8983 may therefore be more useful in combined chemotherapy regimens with P-gp substrates and may be active in platinum and taxane-resistant ovarian cancer. |
Keywords | olaparib; veliparib; CEP-8983; PARP inhibitor; drug Resistance; cell lines; P-glycoprotein; cancer chemotherapy; toxicity |
Research Group | Biomarkers for Cancer group |
Publisher | Wiley |
Journal | Journal of Pharmaceutical Sciences |
ISSN | 0022-3549 |
Electronic | 1520-6017 |
Publication dates | |
Online | 03 Apr 2014 |
20 May 2014 | |
Publication process dates | |
Deposited | 13 Mar 2015 |
Accepted | 28 Feb 2014 |
Output status | Published |
Copyright Statement | This is the pre-peer reviewed version of the following article: Lawlor, D., Martin, P., Busschots, S., Thery, J., O'Leary, J.J., Hennessy, B.T. and Stordal, B. (2014), PARP Inhibitors as P‐glyoprotein Substrates. J. Pharm. Sci., 103: 1913-1920, which has been published in final form at https://doi.org/10.1002/jps.23952. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions |
Web address (URL) | https://onlinelibrary.wiley.com/doi/10.1002/jps.23952 |
Digital Object Identifier (DOI) | https://doi.org/10.1002/jps.23952 |
PubMed ID | 24700236 |
Web of Science identifier | WOS:000336619300034 |
Language | English |
First submitted version |
https://repository.mdx.ac.uk/item/84zq7
Download files
48
total views29
total downloads0
views this month0
downloads this month