INSTITUTO DE INVESTIGACIONES EN RECURSOS NATURALES Y SUSTENTABILIDAD JOSE SANCHEZ LABRADOR S.J.
Unidad Ejecutora - UE
congresos y reuniones científicas
P-gp modulating effect of the pentacyclic triterpenoid betulin, isolated from Ligaria cuneifolia, in multidrug resistant leukemic cells
CARPINELLA M. C.; JORAY M.B.; LAIOLO J.
Congreso; Reunión Anual de Sociedades de Biociencia. SAIC SAFE SAB SAP AACYTAL NANOMED-ar HCS; 2019
Multidrug resistant (MDR) constitutes nowadays one of the major obstacle in cancer therapy, being the efflux of drugs by P-glycoprotein (P-gp) a predominant factor. Plants are recognized as a rich source of metabolites with structural diversity being an invaluable starting point for drug discovery. With the aim of finding promising compounds to modulate MDR phenotype mediated by P-gp, 120 native and naturalized plants collected in the hills of Córdoba, Argentina, were screened on K562 human myelogenous leukemia cell line and its MDR counterpart Lucena 1. Ligaria cuneifolia was one of the most active and thus it was subjected to bioguided isolation to separate the active principle responsible for its activity. This process yielded the triterpenoid betulin (1).Intracellular doxorubicin (DOX) accumulation was determined, at non-cytotoxic concentrations determined by MTT, using flow cytometry. Fluorescence intensity radio (FIR) was calculated as the ratio between the fluorescence intensity of each cell line treated and the fluorescence intensity of its respective solvent control. The activity was confirmed by the MTT reversal assay.Compound 1 increased the accumulation of DOX at a minimum effective concentration (MEC) of 1.56 µM (FIR 1.09±0.04) and increased DOX cytotoxicity by a factor of 3.83± 0.26 at 12.5 µM and 1.29±0.075 at 0.39 µM showing no differences with respect to the same concentrations of verapamil, used as positive control (p-value ≤ 0.05). Compound 1 showed no effect at the MEC on K562 cells.This is the first report regarding compound 1 as an inhibitor of the efflux mediated by P-gp. This triterpenoid could arise as scaffold to obtain novel P-gp inhibitors to use in combination with anticancer drugs for the improvement of leukemia therapies.