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- Title
Hyperforin inhibits P-gp and BCRP activities in chronic lymphocytic leukaemia cells and myeloid cells.
- Authors
Quiney, Claire; Billard, Christian; Faussat, Anne-Marie; Salanoubat, Célia; Kolb, Jean-Pierre
- Abstract
We showed previously that hyperforin (HF), a natural phloroglucinol, stimulated apoptosis in B cell chronic lymphocytic leukaemia cells (CLL) and displayed anti-angiogenic properties. In the present work, we investigated the effects of hyperforin on the activity of P-gp/MDR1, an ABC (ATP-binding cassette) transporter putatively involved in multidrug resistance (MDR). Ex vivo treatment of CLL cells with HF markedly impaired the activity of P-gp, as measured by the inhibition of the capacity of the treated cells to efflux the rhodamine 123 probe. In addition, most CLL cells expressed breast cancer resistance protein (BCRP), another ABC transporter. The activity of BCRP was also inhibited by HF, as assessed by the impaired capacity of HF-treated CLL cells to efflux the specific probe mitoxantrone. The capacity of HF to reverse P-gp and BCRP activity was confirmed in myeloid leukaemia cell lines, notably in HL-60/DNR cells selected for their resistance to daunorubicine and overexpressing P-gp. Our results therefore suggest that HF might be of interest in the therapy of CLL and other haematological malignancies through its potential capacity to revert MDR in addition to its pro-apoptotic properties.
- Publication
Leukemia & lymphoma, 2007, Vol 48, Issue 8, p1587
- ISSN
1042-8194
- Publication type
Journal Article
- DOI
10.1080/10428190701474332