title: Detection of P-glycoprotein expression by tumoral cells with NBDL-CsA, a fluorescent derivative of cyclosporin A.
abstract: The P-glycoprotein (P-gp) molecules which are expressed on multidrug-resistant (MDR) tumor cells efflux a variety of anti-cancer drugs, such as doxorubicin. Though first described as an inhibitor of P-gp function, cyclosporin A (CsA) was more recently shown to behave as a substrate of the P-gp pump. The retention of [3H]CsA was reduced in MDR cells of the human leukemic CEM cell subline, in comparison with the drug-sensitive parental (Par) subline. MDR-CEM cell treatment by the P-gp blockers restored the [3H]CsA retention to the control Par-CEM cell levels. Using a novel fluorescent CsA derivative, [N-epsilon-(4-nitrobenzofurazan-7-yL)-D-Lys8] cyclosporin (NBDL-CsA), we now show that MDR cells can be distinguished from Par cells both at the cell population level (in microculture) and at the single cell level (by use of flow cytometry).
authors.affiliation: Laboratoire d'Immunologie, Strasbourg 1 University, Illkirch, France.
authors.forename: A
authors.initials: A
authors.lastname: Didier
authors.forename: F
authors.initials: F
authors.lastname: Tiberghien
authors.forename: R
authors.initials: R
authors.lastname: Wenger
authors.forename: F
authors.initials: F
authors.lastname: Loor
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D016572:Cyclosporine; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014747:Vinblastine / Q000494:pharmacology
chemical_list: C091682:(N-5-(4-nitrobenzofurazan-7-yl)lysyl(8))cyclosporine; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D014747:Vinblastine; D004317:Doxorubicin; D016572:Cyclosporine