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 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 microM 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 microM 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.
Kwon
Hyog-Young
HY
College of Pharmacy, SungKyunKwan University, Su-Won 440-746, Korea.
Kim
Eun-Hye
EH
Kim
Seung-Whan
SW
Kim
Su-Nam
SN
Park
Jong-Dae
JD
Rhee
Dong-Kwon
DK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D036145:Ginsenosides / Q000633:toxicity*; D006801:Humans; D007624:KB Cells; D007941:Leukemia P388 / Q000188:drug therapy; D008560:Membrane Fluidity / Q000187:drug effects*; D051379:Mice; D009368:Neoplasm Transplantation; D020112:Rhodamine 123
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005456:Fluorescent Dyes; D036145:Ginsenosides; D020112:Rhodamine 123; C097367:ginsenoside Rg3; D004317:Doxorubicin