Effect of Cycloartanes on Reversal of Multidrug Resistance and Apoptosis Induction on Mouse Lymphoma Cells

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.