title: Inhibition of P-glycoprotein transport activity in a resistant mouse lymphoma cell line by diterpenic lactones.
abstract: Multidrug resistance (MDR) is believed to be a major reason for the failure of cancer treatment. It is in most cases caused by the activity of the various ABC transporters, multidrug resistance (MDR) gene-encoded p-glycoproteins that pump anticancer drugs out of the cells. P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP1) are the most important and widely studied members of the ABC superfamily of transporters. The ability of four diterpenic lactones isolated from Euphorbia species to modulate the transport activity of P-gp in mouse lymphoma cells was evaluated by flow cytometry. The reversion of MDR was investigated by using a standard functional assay with rhodamine 123 as a fluorescent substrate analogue of doxorubicin. Verapamil was applied as a positive control. All the compounds were able to reverse the MDR of the tested human MDR1 gene-transfected mouse lymphoma cells, in a concentration-dependent manner from 4 to 40 microg/mL, in a short-term experiment below the cytotoxic doses.
authors.affiliation: Centro de Estudos de Ciências Farmacêuticas, Faculdade de Farmácia da Universidade de Lisboa, Av. das Forças Armadas, 1600-083 Lisboa, Portugal. mjuferreira@ff.ul.pt
authors.forename: Maria-José U
authors.initials: MJ
authors.lastname: Ferreira
authors.forename: Nora
authors.initials: N
authors.lastname: Gyémánt
authors.forename: Ana M
authors.initials: AM
authors.lastname: Madureira
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D028481:Euphorbia / Q000737:chemistry; D007940:Leukemia L5178 / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D045784:Abietanes; D010936:Plant Extracts; C487257:helioscopinolide A; C487258:helioscopinolide B