title: Reduction of cytotoxicity of the alkaloid emetine through P-glycoprotein (MDR1/ABCB1) in human Caco-2 cells and leukemia cell lines.
abstract: The cytotoxicity of the alkaloid emetine was determined in six human cell lines that differ in the expression of ABC transporters, such as multiple drug resistance protein 1 (MDR1/ABCB1) and multidrug resistance associated protein 1 (MRP1/ABCC1). Emetine reveals a substantial cytotoxicity due to apoptosis that is inversely correlated with the expression of MDR1. Confluent Caco-2 cells with high MDR1 activity and the MDR1 over-expressing leukemia cell line CEM/ADR5000 are more resistant towards emetine (EC (50) 250 microM and 2 microM, respectively) than cells with a low expression of MDR1 (Jurkat cells, CCRF-CEM cells, HL-60 cells) or cells which over-express MRP1 (HL-60/AR) (EC (50) between 0.05 microM for CCRF-CEM and 0.17 microM for Jurkat cells). Apparently emetine is a substrate for MDR1 but not for MRP1. Furthermore, emetine is able to up-regulate the expression of MDR1 as shown IN VITRO by real-time PCR and transport activity studies.
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Möller
authors.forename: Johanna
authors.initials: J
authors.lastname: Weiss
authors.forename: Michael
authors.initials: M
authors.lastname: Wink
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000032:analysis*; D045744:Cell Line, Tumor; D004640:Emetine / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans
chemical_list: D018528:ATP-Binding Cassette Transporters; D000903:Antibiotics, Antineoplastic; D004640:Emetine