Effects of tumor necrosis factor alpha, interferon alpha and interferon gamma on non-lymphoid leukemia cell lines: growth inhibition, differentiation induction and drug sensitivity modulation.
The potential role of tumor necrosis factor alpha (TNF alpha), interferon alpha (IFN alpha) and interferon gamma (IFN gamma) in the therapy of non-lymphoid leukemia was studied in ten non-lymphoid leukemia cell lines. All three cytokines tested inhibited the growth of the cell lines. However, a high degree of variability in susceptibility to cytotoxic/cytostatic effect of the cytokines was found among individual cell lines. Some cell lines were sensitive to the antiproliferative action of only one of the cytokines tested, but were resistant to the others. Combinations of two cytokines had additive or synergistic effects and inhibited cell growth to a greater extent than did the individual cytokines alone. In addition to the growth-inhibitory effect, the cytokines induced an apparent cell differentiation. The differentiation of the two most sensitive cell lines, EoL-1 and PL-21, was confirmed using the nitroblue tetrazolium reduction test, by changes in cell morphology, immunophenotype marker profiles and by changes in c-myb expression. Furthermore, we showed that even in the cell lines relatively resistant to the antiproliferative effect of cytokines, such as cell line KCL-22, the inhibition of cell growth could be markedly increased with the DNA-topoisomerase-II-targeted drug, doxorubicin. Our data thus suggest that TNF alpha, IFN alpha and IFN gamma together have a potential role in the immunotherapy of non-lymphoid leukemia in terms of their antiproliferative action, and their ability to induce differentiation and to modulate drug sensitivity.
Kikuchi
A
A
Fujisaki Cell Center, Hayashibara Biochemical Laboratories Inc., Okayama, Japan.
Holán
V
V
Minowada
J
J
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016898:Interferon-alpha; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D007371:Interferon-gamma