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

Abstract

Mouse glioma-26 (G-26) cell line established in this laboratory was used in the study. The in vitro effect of ascorbyl esters, viz., ascorbyl-palmitate (As-P), -stearate (As-S) and mouse interferon-alpha/beta (MulFN-alpha/beta) 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 (24h) of G-26 cells with As-S, As-P or MulFN-alpha/beta, resulted in a dose dependent decrease in cell viability (IC50 = 125 microM As-S; 175 microM As-P and 3.6 x 10(4) U/ml MulFN-alpha/beta) and proliferation (IC50 = 157 microM As-S; 185 microM As-P and 3.6 x 10(4) U/ml MulFN-alpha/beta). A combined exposure to 175 microM As-S and 800 U/ml of MulFN-alpha/beta 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-alpha/beta, but not with human interferon-alpha lymphoblastoid or human interferon-beta. Ascorbyl esters inhibited cytosolic GST activity (1-50 = 15.0 microM As-S and 28.5 microM 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 microM and 2.0 microM 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 microM As-S or 800 U/ml MulFN-alpha/beta.

Interferon effect on glycosaminoglycans in mouse gliomain vitro

“…In this study it was observed that 72 hrs incubation of G-26 cells with various concentrations of MuIFN ~/13 affected their proliferation/viability in a dose dependent manner as previously observed by others using human IFN a and ~ in human glioma studies [30]. This laboratory observed earlier that incubation of G-26 cells for 24 hrs with MulFN c~/[3 affected their proliferation/viability and the ICs0 value was approximately 3.6 x 10 4 U/ml [26]. It was shown by Numa et al [30], that human IFNs (a and 13) at I x 104 U/ml reduced the number of human glioma cells by 50%.…”

A Review of the Nature and Effectiveness of Nutrition Interventions in Adult Males: A Guide for Intervention Strategies

“…Ascorbic acid and ascorbyl esters have been shown to inhibit the proliferation of mouse glioma and human brain tumor cells viz., glioma (U-373) and glioblastoma (T98G) cells and renal carcinoma cells [77][78][79]. Ascorbyl stearate was found to be more potent than sodium ascorbate in inhibiting proliferation of human glioblastoma cells [80].…”

Vitamin C in human health and disease is still a mystery? An overview

“…Ascorbic acid and ascorbyl esters have been shown to inhibit the proliferation of mouse glioma and human brain tumor cells viz., glioma (U-373) and glioblastoma (T98G) cells and renal carcinoma cells [77-79]. Ascorbyl stearate was found to be more potent than sodium ascorbate in inhibiting proliferation of human glioblastoma cells [80].…”