title: The beta-carboline alkaloid harmine inhibits BCRP and can reverse resistance to the anticancer drugs mitoxantrone and camptothecin in breast cancer cells.
abstract: Multidrug resistance (MDR), mediated by highly expressed ABC transporters, is one of the most important mechanisms in tumor cells. Breast cancer resistance protein (BCRP) is a member of the ABC transporter family. This transporter expels different kinds of lipophilic anticancer drugs, which have diffused into the cells. In this study, 96-well plate based assays and flow cytometry analysis were employed to screen natural products for BCRP inhibition. The beta-carboline alkaloid harmine inhibited BCRP in a BCRP overexpressing breast cancer cell line (MDA-MB-231). Harmine reduced resistance to the anticancer drugs mitoxantrone and camptothecin mediated by BCRP and might be an interesting new reversal agent. Harmine did not inhibit P-glycoprotein (P-gp) mediated drug efflux.
authors: University of Heidelberg, Institute of Pharmacy and Molecular Biotechnology, INF 364, 69120 Heidelberg, Germany.
authors: Yonggang
authors: Y
authors: Ma
authors: Michael
authors: M
authors: Wink
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002166:Camptothecin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006247:Harmine / Q000494:pharmacology*; D006801:Humans; D008942:Mitoxantrone / Q000494:pharmacology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D002166:Camptothecin; D006247:Harmine; D008942:Mitoxantrone; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C116614:ABCG2 protein, human