Reversal of Multidrug Resistance by Morning Glory Resin Glycosides in Bacterial Pathogens and Human Cancer Cells

Resin glycosides are complex amphipatic glycolipids of high molecular weight derived from species of the morning glory family (Convolvulaceae). The modulatory effect of microbiologically inactive resin glycosides, evaluated on nosocomial multidrug-resistant (MDR) Gram-positive (Staphylococcus aureus) and -negative (Salmolella typhi and Shigella flexneri) microorganisms, led to the characterization of theses compounds as substrates for efflux pumps. Resin glycosides (25 µg/mL) exerted a potentiation effect on clinically useful antibiotics against the selected tested pathogens by increasing antibiotic susceptibility up to 64-fold. Reversal of MDR by these metabolites was also evaluated in vinblastine-resistant human breast carcinoma cells (MCF-7/Vin). The active non-cytotoxic compounds exerted a potentiation effect on MCF-7/Vin susceptibility to vinblastine over 1906-fold when tested at concentrations of 5 and 25 µg/mL. Through flow cytometry, resin glycosides significantly increased the intracellular accumulation of rhodamine 123 (a substrate for P-glycoprotein, a mammalian effluxing pump). After incubation with a monoclonal antibody, immunofluorescence flow cytometry was used to detect a decreased expression of P-gp by resin glycosides. These results suggest that morning glory oligosaccharides represent potential efflux pump inhibitors for overcoming refractory malignancies by lowering the doses of drugs in combinatorial therapy.