The antileukemic alkaloid fagaronine and the human K 562 leukemic cells: effects on growth and induction of erythroid differentiation.

In view of new antitumor compounds which could exert their therapeutic effect through a combination of cell growth inhibition and cell maturation, we describe here the effects of a novel antileukemic alkaloid, fagaronine, on the growth and the induction of hemoglobin synthesis in the K 562 cell line. We found that fagaronine, after 3 days, reduces in a concentration dependent relationship the cell growth rate without lethality and this effect on the cell growth is irreversible. Reducing the cell growth rate by 50% (IC50 = 3 X 10(-6)M) is sufficient to induce an optimal amount of hemoglobin synthesis (75% benzidine-positive cells, 13-15 pg hemoglobin/cell) after 4 days of culture. Considering the variation of the total intracellular protein content during the response, it appears that fagaronine stimulated mainly hemoglobin synthesis, and to a lesser extent non-hemoglobin proteins. These results suggest that the novel antileukemic alkaloid, fagaronine, can be considered as a potent inducer of differentiated-associated properties in the human K 562 leukemic cells.