INTERFERON ALPHA(2) RECOMBINANT AND EPIDERMAL GROWTH-FACTOR MODULATE PROLIFERATION AND HYPUSINE SYNTHESIS IN HUMAN EPIDERMOID CANCER KB CELLS

We previously found that interferon alpha(2) recombinant (IFN alpha) i ncreases the expression of epidermal growth factor receptor (EGF-R) in the human epidermoid cancer KB cell line. Here we report the effects of IFN alpha and epidermal growth factor (EGF) on KB cell cycle kineti cs. IFN alpha: (1000 i.u./ml) for 48 h decreased the S-phase fraction and diminished the expression of Ki67 and proliferating cell nuclear a ntigen on KB cells. Incubation of IFN alpha-treated KB cells with 10 n M EGF for 12 h reversed these effects. We then studied several biochem ical markers of cell proliferation. Ornithine decarboxylase activity w as decreased to about one-tenth by IFN alpha and partly restored by EG F. Hypusine is contained only in eukaryotic initiation factor 5A and i ts levels are correlated with cell proliferation. IFN alpha decreased hypusine synthesis by 75%; exposure of cells to EGF for 12 h restored hypusine synthesis almost completely. We also studied the effects of I FN alpha on the cytotoxicity of the recombinant toxin TP40, which inhi bits elongation factor 2 through EGF-R binding and internalization. IF N alpha greatly enhanced the TP40-induced inhibition of protein synthe sis in KB cells. In conclusion, IFN alpha, which affects protein synth esis machinery and increases EGF-R expression, enhances the tumoricida l activity of TP40 and hence could be useful in the setting of anti-ca ncer therapy.