Effects of ginsenosides Re and Rg3 on intracellular redox state and cell proliferation in C6 glioma cells

Wai Ng,Mildred S Yang

doi:10.1186/1749-8546-3-8

Abstract

BackgroundCellular redox state is important to cell growth and death. The growth of tumor cells may be modulated by intracellular reduced glutathione/oxidized glutathione (GSH/GSSG). The present study aims to investigate the effects of ginsenosides Re and Rg3 on cellular redox state and cell proliferation in C6 glioma cells.MethodsCultured C6 glioma cells were exposed to various concentrations of either Rg3 or Re for 24 hours. Cell growth and death were measured by the BrdU incorporation assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay respectively. Cellular redox state was determined by free radical production using flow cytometry and GSH/GSSG using spectrofluorometry.ResultsAt a sub-lethal concentration, Re suppressed cell proliferation with a significant decrease in BrdU incorporation. Re did not increase reactive oxygen species (ROS) production but increased GSH/GSSG via increased activity of gamma glutamylcystenyl synthase (γ-GCS). In contrast, Rg3 increased free radical production and reduced GSH/GSSG. The effects of Rg3 were probably due to increased activity of glutathione peroxidase (GPx).ConclusionRe and Rg3 alter cellular redox state of C6 glioma cells in opposite directions. Changes in cellular redox state induced by Re and Rg3 are correlated with the proliferation rates of C6 glioma cells.

Highlights

Cellular redox state is important to cell growth and death
In the presence of free radicals, mainly H2O2, GSH acts as electron donor and is oxidized into GSSG by glutathione peroxidase (GPx)
The present study investigates how Re and Rg3 suppress the growth of C6 glioma cells

Summary

Introduction

Cellular redox state is important to cell growth and death. The growth of tumor cells may be modulated by intracellular reduced glutathione/oxidized glutathione (GSH/GSSG). Cellular redox state can be monitored by intracellular thiol levels, among which the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG) is the most useful [1,2]. In the presence of free radicals, mainly H2O2, GSH acts as electron donor and is oxidized into GSSG by glutathione peroxidase (GPx). The GSSG generated is later converted back to GSH by glutathione reductase (GR) in which reduced nicotinamide adenine dinucleotide phosphate (NADPH) is the hydrogen donor. The GSH/GSSG ratio is increased by the addition of N-acetylcysteine (NAC, a cysteine analogue) [7] or by improved enzymes for glutathione synthesis [8]. Antioxidants or molecules that increase the GSH/GSSG ratio suppress cell prolifera-

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Conclusion