The B-cell lymphoma 2 (BCL2)-inhibitors, ABT-737 and ABT-263, are substrates for P-glycoprotein.
Biochem Biophys Res Commun
; 408(2): 344-9, 2011 May 06.
Article
em En
| MEDLINE
| ID: mdl-21514278
ABSTRACT
Inhibition of BCL2 proteins is one of the most promising new approaches to targeted cancer therapy resulting in the induction of apoptosis. Amongst the most specific BCL2-inhibitors identified are ABT-737 and ABT-263. However, targeted therapy is often only effective for a limited amount of time because of the occurrence of drug resistance. In this study, the interaction of BCL2-inhibitors with the drug efflux transporter P-glycoprotein was investigated. Using (3)H labelled ABT-263, we found that cells with high P-glycoprotein activity accumulated less drug. In addition, cells with increased P-glycoprotein expression were more resistant to apoptosis induced by either ABT-737 or ABT-263. Addition of tariquidar or verapamil sensitized the cells to BCL2-inhibitor treatment, resulting in higher apoptosis. Our data suggest that the BCL2-inhibitors ABT-737 and ABT-263 are substrates for P-glycoprotein. Over-expression of P-glycoprotein may be, at least partly, responsible for resistance to these BCL2-inhibitors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Compostos de Bifenilo
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Proteínas Proto-Oncogênicas c-bcl-2
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Compostos de Anilina
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Nitrofenóis
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido