Berberine is an alkaloid found in many plants, including the Coptis chinensis and Arcangelisia flava. Berberine has been reported to have cytostatic effect on tumor growth. Previously, we have found that the level of glucocorticoid receptors (GR) was significantly higher in hepatoma than in adjacent liver tissues. Using human HepG2 hepatoma cells, we have found that GR were expressed not only in G0-G1 phases, but also in S and G2+M phases. The objective of the present study was to examine the effect of berberine on the expression of GR and its relation to cell cycle progression of HepG2 cells. Continuous exposure of HepG2 cells to various concentrations (1-50 microM) of berberine resulted in growth inhibition in a dose dependent manner. The viability of berberine-treated HepG2 cells was greater than 90% in all treatment groups. Flowcytometric analysis of berberine-treated HepG2 cells showed that the S phase fraction was significantly reduced. GR levels were higher in berberine-treated HepG2 cells than in vehicle (DMSO)-treated cells. In addition, the secretion of alpha-fetoprotein by HepG2 cells was inhibited by berberine. Finally, the berberine induced cell growth arrest was partially reversible in HepG2 cells.