title: Hyperforin inhibits P-gp and BCRP activities in chronic lymphocytic leukaemia cells and myeloid cells.
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.
authors: UMRS 872 INSERM, Université Paris 6, Centre de Recherche des Cordeliers, Paris, France.
authors: Claire
authors: C
authors: Quiney
authors: Christian
authors: C
authors: Billard
authors: Anne-Marie
authors: AM
authors: Faussat
authors: Célia
authors: C
authors: Salanoubat
authors: Jean-Pierre
authors: JP
authors: Kolb
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000494:pharmacology; D022423:Myeloid Cells / Q000187:drug effects; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001643:Bridged Bicyclo Compounds; D009363:Neoplasm Proteins; D013729:Terpenes; D008942:Mitoxantrone; D010696:Phloroglucinol; C001654:hyperforin