Selective toxicity of ginsenoside Rg3 on multidrug resistant cells by membrane fluidity modulation

Multidrug resistance (MDR) is a major problem in cancer chemotherapy. It was previously reported that a red ginseng saponin, 20(S)-ginsenoside Rg 3 could modulate MDR in vitro and extend the survival of mice implanted with ADR-resistant murine leukemia P388 cells. This study examined the cytotoxicity of Rg 3 on normal and transformed cells, along with its effect on the membrane fluidity. The cytotoxicity study revealed that 120 μM of Rg 3 was cytotoxic against a multidrug-resistant human fibroblast carcinoma cell line, KB V20C, but not against normal WI 38 cells in vitro . Flow cytometric analysis using rhodamine 123 as the artificial substrate showed that Rg 3 promoted the accumulation of rhodamine 123 in ADR-resistant murine leukemia P388 cells in vivo . Fluorescence polarization studies using the hydrophilic fluorescent probe, DPH, and hydrophobic probe, TMA-DPH, showed that 20 μM Rg 3 induced a significant increase in fluorescence anisotropy in KB V20C cells but not in the parental KB cells. These results clearly show that Rg 3 decreases the membrane fluidity thereby blocking drug efflux.