Inhibition of human glioma cell proliferation and glutathione S-transferase by ascorbyl esters and interferon.

The in vitro effect of ascorbyl esters (ascorbyl-stearate [As-S] and -palmitate [As-P]) and interferon (recombinant human interferon-a2b [rHuIFN-a2b]) on human glioma (U-373) cell proliferation, viability and glutathione-S-transferase (GST) activity was studied. The effect of As-S, As-P and rHuIFN-a2b on cell proliferation and viability was evaluated by [3H] Thymidine incorporation and colorimetric MTT assays, respectively. Incubation of glioma cells with As-S, As-P or rHuIFN-a2b for 24 h resulted in a dose dependent inhibition of cell proliferation (IC50 = 68.0 microM As-S, 86.0 microM As-P and 47.3 Units/ml rHuIFN-a2b), and moderate decrease of cell viability. It was found that As-S was a more efficient inhibitor of cell proliferation, viability and GST activity than As-P. GST from U-373 cells was purified. The activity of purified GST towards 1-chloro-2,4-dinitrobenzene (CDNB) was inhibited in a dose dependent manner by ascorbyl esters (I-50 = 27.5 microM As-S and 56.0 microM As-P) but not by rHuIFN-a2b. GST activity of cytosol isolated from U-373 cells which were previously treated with As-S (150 microM) or rHuIFN-a2b (150 units/ml) for 0, 2, 5, 10, 20 and 30 min was sharply decreased during 5 to 10 min of treatment and increased at longer durations of treatment.