Actinomycin V as a Potent Differentiation Inducer of F5-5 Friend Leukemia Cells

The cell differentiation system of Friend leukemia cells was applied to screening for new types of antitumor antibiotics. F5-5, Friend leukemia cells, were the most suitable for the assay system due to the stability of their response on repeated culture passages. Antibiotics like mitomycin C, adriamycin and actinomycin D, but not cycloheximide, did not induce detectable benzidine-positive cells among the F5-5 cells in the concentration ranges tested. Among the culture fluids of one thousand and fifty-one streptomycete strains subjected to the assay system, actinomycin V, FL-518 and FL-657 were found to be the most active as inducers. Actinomycin V possessing l-4-ketoproline as a substitute for l-proline of actinomycin D at a concentration of 1.0ng/ml caused 39.7% of the F5-5 cells to become benzidine-positive. Furthermore, actinomycin V inhibited the colony formation of F5-5 cells in the soft agar medium at a concentration of 0.004 ng/ml.