Reversal of Daunomycin and Vinblastine Resistance in Multidrug-Resistant P388 Leukemiain vitrothrough Enhanced Cytotoxicity by Triterpenoids

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Abstract
Examined in vitro were the effects of some triterpenoids from Panax (Araliaceae) and Glycyrrhiza (Leguminosae) spp. on the sensitivity to daunomycin (DAU) and vinblastine (VBL) of adriamycin (ADM)-resistant P388 leukemia cells (P388/ADM), which were resistant to multiple anticancer drugs. Quasipanaxatriol, 20(S)-protopanaxatriol, ginsenoside Rh2, and compound K greatly enhanced the cytotoxicity of the anti-cancer drugs in P388/ADM cells. The extent of enhancement was different among the triterpene compounds; the 4- to 46-fold increase in DAU cytotoxicity was observed in P388/ADM cells in the presence of non-toxic or marginally toxic concentrations of individual compounds, while those for VBL were in the ratios of 2- to 37-fold. The maximum increase in cytotoxicity was observed with 50 µM quasipanaxatriol; the resistance indices defined to be the ratios of the IC50 values for P388/ADM and P388 parental cells decreased from 79 to 1.7 and from 180 to 4.9 in the cases of DAU and VBL, respectively. The reversal of DAU resistance in P388/ADM by quasipanaxatriol could be explained by the effective accumulation of the drugs mediated by the DAU-efflux blockage.

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