Effects of recombinant human interferon-alpha, beta and gamma on the antiproliferative activity of cytarabine in K562 human myeloid leukemia clonogenic cells.

Abstract

The effects of recombinant human interferon-alpha, beta and gamma (IFN) on the antiproliferative activity of cytarabine (ara-C) in K562 human myeloid leukemia clonogenic cells were studied in an agar capillary microassay. The addition of IFN-alpha did not affect the antiproliferative activity of ara-C in K562 cultures treated with low concentrations of ara-C: 10-50 nM, whereas in those treated with high concentrations of ara-C: 100-500 nM, IFN-alpha significantly reduced the antiproliferative activity of ara-C. The addition of 3 x 10(4) U/ml IFN-alpha to ara-C-treated K562 cultures increased the IC50 of ara-C on day 5 from 102 to 214 nM, i.e. ara-C+IFN-alpha was about twofold less potent than ara-C alone. Low concentrations of IFN-beta and IFN-gamma did not affect the antiproliferative activity of ara-C on K562 colonies, but high concentrations of these two interferons reduced the antiproliferative activity of ara-C. The addition of 4 x 10(3) U/ml IFN-beta or 10(4) U/ml IFN-gamma increased the IC50 of ara-C on day 5 to 304 nM or to 316 nM, respectively, i.e. ara-C+IFN-beta or IFN-gamma was about threefold less potent than ara-C alone. The significant reduction of the desired antiproliferative activity of ara-C by the three interferons was reproduced in liquid suspension cultures of K562 cells on day 4 in the following order: IFN-gamma greater than IFN-beta greater than IFN-alpha. The present negative interactions of the three interferons with ara-C particularly at high concentrations, may caution against the clinical use of the combination of ara-C and interferon in the treatment of myeloid leukemia patients.