New combination of 5-fluorouracil and interferon-gamma effective against human myeloid leukemia in vitro.
The therapeutic potential of recombinant interferon gamma (IFN gamma) alone or in combination with two cytotoxic drugs - 5-fluorouracil (5-FU) and cytosine arabinoside (Ara-C) - was studied in vitro on two myeloid leukemia systems: HL60 promyelocytic cell line and chronic granulocytic leukemia (CGL) progenitor cells. When applied individually, IFN gamma and the drugs inhibited in a dose-dependent manner HL60 cell colony formation in semisolid culture. Moreover, IFN gamma or the cytotoxic drugs dose-dependently reduced the colony formation of CGL progenitor cell in agar. When added in combination, IFN gamma potentiated synergistically the inhibitory action of 5-FU in both systems. The most pronounced potentiation was detected at concentrations of 0.5 microgram/ml 5-FU and 50 U/ml IFN gamma. On the contrary, the antiproliferative effect of Ara-C was enhanced only subadditively when combined with IFN gamma. In view of the present findings, which are supported by new evidence from the literature, the use of 5-FU in leukemia should be reconsidered. The results further imply the potential value of combined treatment of 5-FU and IFN gamma in leukemia.
Kafka
M
M
Haematology Laboratory, Faculty of Medical Sciences, Ben-Gurion University of Negev, Beer Sheva, Israel.
Nathan
I
I
Dvilansky
A
A
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*; D014410:Tumor Stem Cell Assay
D011994:Recombinant Proteins; D003561:Cytarabine; D007371:Interferon-gamma; D005472:Fluorouracil