Cytotoxicity of Human β-Interferon for Differentiating Leukemic HL-60 Cells

We examined the effect of human interferon (HulFN) -α and -β on the proliferation and differentiation induced by dimethyl sulfoxide (DMSO) of HL-60 human promyelocytic leukemia cells into mature granulocytes. Neither HulFN-α nor -β, alone, from 1 to 1000 IU/ml, nor the homologous mock HulFN preparations affected HL-60 cell differentiation or proliferation. Whereas the combination of HulFN-α (10 to 1000 IU/ml) with DMSO also did not affect the proliferation or differentiation of HL-60 cells, the addition of HulFN-β (1000 IU/ml) and DMSO (1.25%) to growing cultures reduced cell viability as much as 14% of that observed for cells treated with DMSO alone or to 4% of that observed for either untreated cells or those treated with HulFN-β alone. The cytotoxic effect declined with decreasing concentrations of HulFN-β. The cytotoxic effect of DMSO and HulFN-β was exerted only as cells began to differentiate. Removal of HulFN-β at Day 2 did not reverse the cytotoxic effect, and addition of HulFN-β at Day 2 did not inhibit cell proliferation. Addition of HulFN-β to postmitotic cells on Day 4 after DMSO treatment did not affect proliferation but did slow differentiation. The cytotoxic and anti-differentiative effects of naturally produced HulFN-β were confirmed with highly purified recombinant HulFN-β. Undifferentiated HL-60 cells were resistant to the antiviral effects of HulFN-β, requiring 4 to 6 times the concentration to protect 50% of the cells against vesicular stomatitis virus as that needed to produce a cytotoxic or antidifferentiative effect. The profoundly cytotoxic effects of HulFN-β reported here may provide a model to study this interferon in combination with inducers of leukemic cell differentiation as a possible strategy in cancer therapy.