Interferon-beta inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines.
The growth inhibitory effect of IFN-beta was evaluated in 5 human glioma cell lines (AO2V4, GJC, GJR, NN and NNR) and in normal astrocyte cultures (SC and TM). All 5 glioma cell lines showed an anti-proliferative response to IFN-beta whereas normal glial cells were non-responsive. IFN-beta at 10, 100 and 500 U/ml lead to a 30%, 70% and 80% relative decrease in cell number after 12 days, respectively in AO2V4 cells. GJC and GJR cell lines also responded significantly to the lowest concentration of IFN-beta tested and at 500 U/ml the relative cell number decreased 55%. The NN and NNR cells were the least responsive to IFN-beta with maximum growth inhibition of 30% at 500 U IFN-beta/ml. Following treatment with IFN-beta, AO2V4, GJC, GJR and normal astrocytes all expressed mRNA encoding the anti-viral protein, 2-5A synthetase demonstrating that IFN-beta bound to receptors on all four cell lines and activated signal transduction pathways required for induction of an anti-viral protein. A determination of the relative number of viable cells showed that none of these cells exhibited a significant decrease in cell viability. Since the antiproliferative response to IFN-beta was not primarily due to cell death, the effect of IFN-beta on cell cycle progression was evaluated by flow cytometry. All treated glioma cell lines showed a relative increase in proportion of cells in S phase. AO2V4 cells had a 50%-80% increase in the percentage of cells in S phase, whereas GJC, GJR and NNR had percentage increases of 20%-40%. IFN-beta treatment of normal astrocytes did not significantly alter their cell cycle profile. These data suggest that IFN-beta exerts its antiproliferative effect on glioma cells by arresting the ordered progression through S phase or decreasing entry into G2/M phase of the cell cycle.
Garrison
J I
JI
Department of Zoology, Arizona State University, Tempe 85208-1501, USA.
Berens
M E
ME
Shapiro
J R
JR
Treasurywala
S
S
Floyd-Smith
G
G
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D005910:Glioma; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016196:S Phase / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D016899:Interferon-beta; D007371:Interferon-gamma