Inhibition of cell proliferation and glutathione S-transferase by ascorbyl esters and interferon in mouse glioma.
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.
Naidu
A K
AK
Department of Neurology, College of Medicine, University of South Florida, Tampa 33612.
Wiranowska
M
M
Kori
S H
SH
Roetzheim
K C
KC
Kulkarni
A P
AP
D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D004359:Drug Therapy, Combination; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D007370:Interferon Type I / Q000494:pharmacology*; D051379:Mice; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; C036225:ascorbyl monostearate; D005982:Glutathione Transferase; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid