MODULATORY EFFECT OF NATIVE AND NATURALIZED PLANT EXTRACTS ON P-GLYCOPROTEIN MULTIDRUG TRANSPORTER IN CHRONIC MYELOGENOUS LEUKEMIA CELLS

JORAY M.B.; GONZÁLEZ M.L.; CARPINELLA M. C.; LAIOLO J.; PALACIOS S. M.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencia; 2017

P-Glycoprotein (P-gp) is a unique ATP-dependent transmembrane efflux pump that plays a significant role in the intracellular decreasing of anticancer drugs. Over-expression of this protein leads to the development of multidrug resistance (MDR) and constitutes nowadays one of the main obstacles to successful chemotherapy. Natural product constituents are diverse and they have potential to offer novel chemical scaffolds and leads. With the aim of finding new novel P-gp modulators, one hundred and twenty native and naturalized plants collected from central region of Argentina were screened over K562 human myelogenous leukemia cell line and its MDR counterpart Lucena 1. Ethanolic extracts dissolved in DMSO at 100 and 50 g/ml were assayed for their cytotoxicity activity by MTT. Intracellular doxorubicin accumulation was determined, at non-cytotoxic concentration of each extract, using high throughput 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 DMSO control.Nineteen extracts exhibited significant P-gp modulating effects (*p-values ≤ 0.05) at 100 g/ml, being the most relevant: Ligaria cuneifólia (FIR: 1,75±0,10*); Jarava ichu (FIR: 1,70±0,24*); Senecio viravira (FIR: 1,70±0,30*); Melinis repens (FIR: 1,62±0,22*); Senecio madagascariensis (FIR: 1,62±0,17*). On the other hand, Aloysia gratissima (FIR: 1,30±0,10*) and Eupatorium viscidum (FIR: 1,23±0,06*) were effective at 50 g/ml. The minimum inhibitory concentration of the extracts tested will be presented.According to the results obtained, these plants could be source of compounds capable to reverse the MDR phenotype and sensitize the leukemia cells to conventional chemotherapy.Keywords: P-gp, natural products, multidrug resistance.