Effects of ascorbic acid and sodium selenite on growth and redifferentiation in human hepatoma cells and its mechanisms.

After being treated with ascorbic acid (AA) 3 mM + sodium selenite (SS) 1.5 microM, the growth rate and mitotic index of human hepatoma cells BEL-7402 decreased remarkably. The indexes related to cell malignancy were improved, such as cell surface charge obviously decreased, the electrophoresis rate fell from 1.76 microns.s-1.V-1.cm-1 to 0.93, the average of alpha-fetoprotein (alpha-FP) content decreased from 341 micrograms.g-1 protein to 92, and gamma-glutamyl-transpeptidase (gamma-GT) activity from 0.76 U.g-1 protein to 0.19. The indexes related to cell differentiation were affected favourably, such as the level of tyrosine-alpha-ketoglutarate transaminase (TAT) activity increased from 14.2 mumol.g-1 protein to 49.0, and the colonogenic potential decreased 95.3%. These results indicated that hepatoma cells had been successfully induced to redifferentiation by AA + SS. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were significantly higher, while the activity of catalase (CAT) was slower in the treated group than in the control group. The malondialdehyde (MDA) content decreased slightly, reduced glutathione (GSH) decreased sharply, and H2O2 content increased dramatically. In conclusion, these results indicate that the combination of ascorbic acid and sodium selenite may induce the redifferentiation of hepatoma cells and inhibit cell growth by virtue of enhancing the activities of antioxidative enzymes and reducing the formation of H2O2, and altering the cell redox status. The combination of ascorbic acid and sodium selenite may be a potent anticancer treatment option for human hepatoma cells.