bafilomycin-a1 and phenothiazine

P-glycoprotein, member of the B-subfamily of the ATP-binding cassette (ABC) superfamily (e.g., ABCB1), has been demonstrated to confer resistance to clinically relevant anticancer drugs. Paradoxically, ABCB1-expressing multidrug resistant (MDR) cells are hypersensitivity or collateral sensitivity to non-toxic drugs. In this report, we demonstrate the capacity of trifluoperazine (TFP), a calmodulin inhibitor, to confer a collateral sensitivity onto ABCB1-overexpressing MDR cells. We show TFP-induced collateral sensitivity to be linked to ABCB1 expression and ATPase activity, as such phenotype is abolished in ABCB1-knockout MDR cells (CHO

Topics: Apoptosis; ATP Binding Cassette Transporter, Subfamily B; Cell Line; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Macrolides; Oxidation-Reduction; Phenothiazines; Reactive Oxygen Species; Trifluoperazine