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KMID : 0043320080310020171
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Archives of Pharmacal Research
2008 Volume.31 No. 2 p.171 ~ p.177
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Selective Toxicity of Ginsenoside on Multidrug Resistant Cells by Membrane Fluidity Modulation
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Kwon Hyog-Young
Kim Eun-Hye
Kim Seung-Whan
Kim Su-Nam
Park Jong-Dae
Rhee Dong-Kwon
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Abstract
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Multidrug resistance (MDR) is a major problem in cancer chemotherapy. It was previously reported that a red ginseng saponin, 20(S)-ginsenoside Rg3 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 Rg3 on normal and transformed cells, along with its effect on the membrane fluidity. The cytotoxicity study revealed that 120 μM of Rg3 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 Rg3 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 Rg3 induced a significant increase in fluorescence anisotropy in KB V20C cells but not in the parental KB cells. These results clearly show that Rg3 decreases the membrane fluidity thereby blocking drug efflux
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KEYWORD
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Panax ginseng, Ginsenosides, 20(s)-ginsenoside Rg3, Multidrug resistance (MDR)
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