sdz-280-446 and Leukemia--T-Cell

The P-glycoprotein (Pgp) molecules which are expressed on multidrug resistant (MDR) tumor cells can efflux a variety of cytostatics. In both normal and tumoral epitheliums, Pgp molecules are selectively expressed on the apical surface of the epithelial cells. Such a distribution seems to be responsible for the transcellular transport of Pgp substrates, including cyclosporin A (CsA), from the basal to the apical side. Some normal lymphoid cells also express small amounts of Pgp molecules, for as yet unknown functions. Nevertheless, the sensitivity of their mitogen-induced proliferation to cytostatics, including doxorubicin and CsA, could be increased by the Pgp blockers. Using isotopically-labeled CsA and tumoral lymphoid cell lines, we now show a higher CsA retention in Pgp-lacking parental ('Par') cells than in Pgp-expressing MDR cells. The Pgp blockers can restore the CsA retention in the MDR cells to its level in the Par cells.

Topics: Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cyclosporine; Cyclosporins; Daunorubicin; Doxorubicin; Drug Resistance, Multiple; Flow Cytometry; Humans; Immunosuppressive Agents; Leukemia, Monocytic, Acute; Leukemia, T-Cell; Mice; Peptides, Cyclic; Rhodamines; Tumor Cells, Cultured; Verapamil; Vinblastine