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

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  • Drug Efficacy and Safety
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Abstract

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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Abbreviations

ADR:

adriamycin

DPH:

1, 6-diphenyl-1,3,5,-hexatriene

MDR:

multi-drug resistance

P-gp:

Phospho-glycoprotein

TMA-DPH:

1-[4-(trimethyl-ammonio)-phenyl]-6-phenyl-1,3,5,-hexatriene

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Authors and Affiliations

  1. College of Pharmacy, SungKyunKwan University, Su-Won, 440-746, Korea

    Hyog-Young Kwon, Eun-Hye Kim & Dong-Kwon Rhee

  2. Department of Pharmacology, University of Ulsan College of Medicine, Seoul, 138-736, Korea

    Seung-Whan Kim

  3. KIST Gangneung Institute, Gangneung, 210-340, Korea

    Su-Nam Kim

  4. Ginseng Science Research Group, KT & G Central Research Institute, Daejeon, 305-805, Korea

    Jong-Dae Park

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  1. Hyog-Young Kwon
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  2. Eun-Hye Kim
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Correspondence to Dong-Kwon Rhee.

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These two authors contributed equally to this work.

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Kwon, HY., Kim, EH., Kim, SW. et al. Selective toxicity of ginsenoside Rg3 on multidrug resistant cells by membrane fluidity modulation. Arch. Pharm. Res. 31, 171–177 (2008). https://doi.org/10.1007/s12272-001-1137-y

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