REVERSAL OF DAUNOMYCIN AND VINBLASTINE RESISTANCE IN MULTIDRUG-RESISTANT P388 LEUKEMIA IN-VITRO THROUGH ENHANCED CYTOTOXICITY BY TRITERPENOIDS

Examined in vitro were the effects of some triterpenoids hom Panax (Ar aliaceae) and Glycyrrhiza (Leguminosae) spp. on the sensitivity to dau nomycin (DAU) and vinblastine (VBL) of adriamycin (ADM)-resistant P388 leukemia cells (P388/ADM), which were resistant to multiple anticance r drugs. Quasipanaxatriol, 20(S)-protopanaxatriol, ginsenoside Rh-2, a nd compound K greatly enhanced the cytotoxicity of the anticancer drug s 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 nontoxic or marginal ly toxic concentrations of individual compounds, while those for VBL w ere in the ratios of 2- to 37-fold. The maximum increase in cytotoxici ty was observed with 50 mu M quasipanaxatriol; the resistance indices defined to be the ratios of the IC50 values for P388/ADM and P388 pare ntal cells decreased from 79 to 1.7 and from 180 to 4.9 in the cases o f DAU and VBL, respectively. The reversal of DAU resistance in P388/AD M by quasipanaxatriol could be explained by the effective accumulation of the drugs mediated by the DAU-efflux blockage.