Reversal of Multidrug
Resistance by Morning Glory
Resin Glycosides in Human Breast Cancer Cells
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Abstract
Reversal of multidrug resistance (MDR) by thirty resin
glycosides
from the morning glory family (Convolvulaceae) was evaluated in vinblastine-resistant
human breast carcinoma cells (MCF-7/Vin). The effects of these amphipathic
compounds on the cytotoxicity and P-glycoprotein (P-gp)-mediated MDR
were estimated with the sulforhodamine B colorimetric assay. Active
noncytotoxic compounds exerted a potentiation effect of vinblastine
susceptibility by 1- to over 1906-fold at tested concentrations of
5 and 25 μg/mL. Murucoidin V (<b>1</b>) enhanced vinblastine
activity 255-fold when incorporated at 25 μg/mL and also, based
on flow cytometry, significantly increased the intracellular accumulation
of rhodamine 123 with the use of reserpine as a positive control for
a MDR reversal agent. Incubation of MCF-7/Vin cells with <b>1</b> caused an increase in uptake and notably lowered the efflux rate
of rhodamine 123. Decreased expression of P-glycoprotein by compound <b>1</b> was detected by immunofluorescence flow cytometry after
incubation with an anti-P-gp monoclonal antibody. These results suggest
that resin glycosides represent potential efflux pump inhibitors for
overcoming MDR in cancer therapy