Effects of recombinant human interferon-alpha, beta and gamma on the antiproliferative activity of cytarabine in K562 human myeloid leukemia clonogenic cells
✍ Scribed by Dr H. T. Hassan; C. Tsiriyotis; H. R. Maurer
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 574 KB
- Volume
- 10
- Category
- Article
- ISSN
- 0278-0232
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✦ Synopsis
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 lo4 U/ml IFN-alpha to ara-C-treated K562 cultures increased the IC,, 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 IFNbeta 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 lo3 U/ml IFN-beta or lo4 U/ml IFN-gamma increased the IC,, of ara-C on day 5 to 304 nM or to 3 16 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 > IFN-beta > IFNalpha. 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.