PARP inhibitors as P-glyoprotein substrates
make_name_string expected hash reference 
ORCID: https://orcid.org/0000-0002-7892-951X
(2014)
PARP inhibitors as P-glyoprotein substrates.
Journal of Pharmaceutical Sciences, 103
(6)
.
pp. 1913-1920.
ISSN 0022-3549
[Article]
(doi:10.1002/jps.23952)
|
PDF
- First submitted uncorrected version (with author's formatting)
Download (474kB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Additional Information: | Article first published online: 3 APR 2014 |
| Keywords (uncontrolled): | olaparib; veliparib; CEP-8983; PARP inhibitor; drug Resistance; cell lines; P-glycoprotein; cancer chemotherapy; toxicity |
| Research Areas: | A. > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group |
| Item ID: | 14450 |
| Notes on copyright: | 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 |
| Useful Links: | |
| Depositing User: | Britta Stordal |
| Date Deposited: | 13 Mar 2015 14:20 |
| Last Modified: | 21 Feb 2023 14:14 |
| URI: | https://eprints.mdx.ac.uk/id/eprint/14450 |
Actions (login required)
 |
View Item |
Statistics
Additional statistics are available via IRStats2.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)