Effects of 5-aza-2'-deoxycytidine and interferon-alpha on differentiation and oncogene expression in HL-60 myeloid leukemic cells.

The antineoplastic effects of 5-aza-2'-deoxycytidine (5-AZA-CdR) and interferon-alpha (IFN-alpha) on human HL-60 myeloid leukemic cells were investigated. 5-AZA-CdR and IFN-alpha in combination produced a greater inhibition of DNA synthesis and cell growth than either agent alone. The co-treatment produced a synergistic reduction in the clonogenicity of the HL-60 leukemic cells. In addition, this combination also produced a greater reduction in mRNA expression for c-myc than each agent alone. This antileukemic action produced by 5-AZA-CdR and IFN-alpha in combination correlated with the increase in induction of differentiation of the HL-60 leukemic cells. These results suggest that 5-AZA-CdR and IFN-alpha in combination produces an enhancement of their antineoplastic action on HL-60 human myeloid leukemic cells.