Synergistic effect of ginsenoside Rg3 with verapamil on the modulation of multidrug resistance in human acute myeloid leukemia cells

The pharmacological modulatory effects of 20(S)-ginsenoside Rg3 (20S-Rg3) on multidrug resistant cancer cells are reported in the present study. The effects of 20(S)-Rg3 on the modulation of doxorubicin (DOX) and vincristine (VCR) resistance were examined in the HL60 multidrug resistant subline of human acute myeloid leukemia cells. Results demonstrated that 20S-Rg3 is as effective as verapamil (Vp) for modulating the high degree primary DOX resistance and low degree VCR cross-resistance expressed by the H160 cell line. Furthermore, the present study demonstrates for the first time, using isobologram analysis, that the combination of 20S-Rg3 and Vp enhances the reversal of DOX and VCR resistance in a supra-additive or at least an additive manner. These results indicate that 20S-Rg3 may be used as a Vp synergizer or as a promising alternative to Vp in the chemosensitization of multidrug resistant acute myeloid leukemia, with far fewer side effects.