Detection of P-glycoprotein expression by tumoral cells with NBDL-CsA, a fluorescent derivative of cyclosporin A

The P-glycoprotein (P-gp) molecules which expressed on multidrug-resistant (MDR) tumor 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 [H-3]CsA was reduced in MDR cells of the human leukemic GEM cell subline, in comparison with the drug-sensitive parental (Par) subline, MDR-GEM cell treatment by the P-gp blockers restored the [H-3]CsA retention to the control Par-GEM cell levels, Using a novel fluorescent GsA derivative, [N-epsilon-(4-nitrobenzofurazan-7-yl)-D-Lys(8)] 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).