PARP Inhibitors as P-glyoprotein Substrates
| Autor: | Bryan T. Hennessy, Denise Lawlor, Patricia Martin, Britta K. Stordal, Steven Busschots, Julien Thery, John J. O'Leary |
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| Rok vydání: | 2013 |
| Předmět: |
biology
Veliparib Chemistry Pharmaceutical Science Combination chemotherapy Pharmacology Poly(ADP-ribose) Polymerase Inhibitors medicine.disease Olaparib chemistry.chemical_compound Cell Line Tumor PARP inhibitor biology.protein medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Valspodar Enzyme Inhibitors Ovarian cancer P-glycoprotein Zosuquidar medicine.drug |
| Zdroj: | Journal of pharmaceutical sciences. 103(6) |
| ISSN: | 1520-6017 0022-3549 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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