title: Effect of cycloartanes on reversal of multidrug resistance and apoptosis induction on mouse lymphoma cells.
abstract: The ability of fifteen cycloartanes, isolated from Euphorbia species, to reverse multidrug resistance (MDR) and apoptosis induction in L5178Y mouse lymphoma cells, including its multidrug-resistant subline, was studied by flow cytometry. Reversion of MDR was investigated using a standard functional assay with rhodamine 123 as a fluorescent substrate analogue. For the evaluation of apoptosis, the cells were stained with FITC-labeled annexin V and propidium iodide. The majority of the compounds were able to reverse MDR of the tested human MDR1 gene-transfected mouse lymphoma cells. Some of the compounds were able to induce moderate apoptosis in the PAR cell line, but this effect was less effective on multidrug-resistant cells. The results indicate that cycloartanes can be substrates of ABC transporters, which might compete with certain anticancer chemotherapeutics.
authors.affiliation: Centro de Estudos de Ciências Farmacêuticas, Faculdade de Farmácia da Universidade de Lisboa, Av. das Forças Armadas, 1600-083 Lisboa, Portugal.
authors.forename: Ana Margarida
authors.initials: AM
authors.lastname: Madureira
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Annamária
authors.initials: A
authors.lastname: Molnár
authors.forename: Andreas
authors.initials: A
authors.lastname: Varga
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Abreu
authors.forename: Maria-José U
authors.initials: MJ
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D028481:Euphorbia / Q000737:chemistry; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D014315:Triterpenes; C085352:cycloartane