Synergistic anticellular effect of a combination of β-interferon and retinoic acid against U937 cells

Both human beta-interferon (IFN-beta) and retinoic acid (RA) are able to induce the differentiation of the human histiocytic lymphoma cell line U937, but neither one alone can effectively eliminate the leukemic cells. When U937 cells are incubated with a combination of IFN-beta (200 units/ml) and RA (0.1-1.0 microM), extensive cell death can be observed as early as day 3 posttreatment, and IFN-beta alone at a concentration as high as 10(4) units/ml is ineffective. These data suggest that there is a strong synergistic cell killing effect between IFN-beta and RA against the U937 cells. This effect is so highly selective that similar enhancement has not been detected using a closely related cell line, HL-60, and RA enhances neither IFN-alpha nor IFN-gamma in the killing of U937 cells. The mechanism of such synergism is unknown in the present study, but it appears that cytostasis or promotion of differentiation alone cannot account for this phenomenon since neither activity is enhanced to any appreciable extent.