Inhibition of cell proliferation and glutathione S-transferase by ascorbyl esters and interferon in mouse glioma

Publisher Website
Google Scholar
Abstract
Mouse glioma-26 (G-26) cell line established in this laboratory was used in the study. Thein vitro effect of ascorbyl esters, viz., ascorbyl-palmitate (As-P), -stearate (As-S) and mouse interferon-α/β (MulFN-α/β) on the glioma cell viability, proliferation and glutathione S-transferase (GST) activity was investigated. Cell viability and proliferation were examined by colorimetric MTT assay and [3H]-thymidine incorporation, respectively. Incubation (24 h) of G-26 cells with As-S, As-P or MulFN-α/β, resulted in a dose dependent decrease in cell viability (IC50=125μM As-S; 175μM As-P and 3.6×104 U/ml MulFN-α/β) and proliferation (IC50=157μM As-S; 185μM As-P and 3.6×104 U/ml MulFN-α/β). A combined exposure to 175 μM As-S and 800 U/ml of MulFN-α/β resulted in a greater than an additive effect on cell viability and proliferation. The inhibition of cell proliferation/viability by interferon was species specific and was observed only with homologous MulFN-α/β, but not with human interferon-α lymphoblastoid or human interferon-β. Ascorbyl esters inhibited cytosolic GST activity (1–50=15.0 μM As-S and 28.5 μM As-P) towards 1-chloro-2,4-dinitrobenzene in a dose dependent manner. The apparent Ki values for affinity purified GST, deduced from Dixon plots were 0.95 μM and 2.0 μM for As-S and As-P, respectively. Significant inhibition of GST was also observed in the cytosol isolated from G-26 cells exposed to 300 μM As-S or 800 U/ml MulFN-α/β.