This study was designed to investigate the effect of curcumin (diferuloylmethane) on the proliferation and apoptosis of hepatic stellate cells (HSC). The cell line HSC-T6 (1.25 x 10(5) cells/mL) was incubated with curcumin and HSC proliferation was detected by a methyl thiazolyl tetrazolium colorimetric assay. HSC apoptosis was detected by flow cytometry, transmission electron microscope and agarose gel electrophoresis. HSC proliferation was significantly inhibited in a concentration-dependent manner (10.6 to 63.5%) after incubation with 20-100 microM curcumin, compared with a control group. At 20, 40, and 60 microM, after 24 h of incubation, curcumin was associated with a significant increase in the number of HSC in the G2/M phase, and a significant decrease in cell numbers in the S phase (P < 0.05). At these concentrations, curcumin was also associated with an increase in the apoptosis index of 15.3 +/- 1.9, 26.7 +/- 2.8, and 37.6 +/- 4.4%, respectively, compared to control (1.9 +/- 0.6%, P < 0.01). At 40 microM, the curcumin-induced apoptosis index at 12, 24, 36, and 48 h of incubation was 12.0 +/- 2.4, 26.7 +/- 3.5, 33.8 +/- 1.8, and 49.3 +/- 1.6%, respectively (P < 0.01). In conclusion, curcumin inhibits the in vitro proliferation of HSCs in the G2/M phase of the cell cycle and also induces apoptosis in a concentration- and time-dependent manner. The in vivo effect of curcumin on HSCs requires further investigation.