Anti-MDR Effects of Quercetin and its Nanoemulsion in Multidrug-Resistant Human Leukemia Cells

Abstract

Background: Quercetin has potential against the Multidrug Resistance (MDR) phenotype, but with low bioavailability. The increase in the bioavailability can be obtained with nanostructures.

Objective: To analyze the effects of quercetin and its nanoemulsion on MDR and non-MDR cells.

Methods: We used high-pressure homogenization for nanoemulsion production; Trypan Blue for cytostatic/cytotoxicity assays; Epifluorescence microscope (with specific probes) for apoptosis and DNA damage; Real-Time PCR for gene expression; AutoDock Vina for docking and Flow Cytometry for efflux analysis. Quercetin exerted antiproliferative impact, induced apoptosis, necrosis and DNA damage on cells.

Results: Quercetin combined with vincristine showed an effect similar to verapamil (an ABCB1 inhibitor), and docking showed that it binds to ABCB1 in a similar region. Quercetin was also capable of altering ABCB1 gene expression. Quercetin in nanoemulsion maintained the cytotoxic and cytostatic effects of quercetin, which may increase bioavailability. Besides, the unloaded nanoemulsion was able to inhibit per se the efflux activity of ABCB1, demonstrating pharmacological action of this structure.

Conclusion: Quercetin may be considered as a prospective drug to overcome resistance in cancer cells and its nanoemulsion can be an alternative for in vivo application.

Keywords: ABCB1; DNA damage.; Docking; apoptosis; nanoemulsion; proliferation inhibition.