Comparative effects of fagaronine, adriamycin and aclacinomycin on K562 cell sensitivity to natural-killer-mediated lysis. Lack of agreement between alteration of transferrin receptor and CD15 antigen expressions and induction of resistance to natural killer

Abstract

Little is known about membrane target antigens for natural killer (NK) cells. Transferrin receptor and CD15 antigen might be two of these target structures. A novel antileukemic alkaloid, fagaronine, is able to induce hemoglobin synthesis in the K562 cell line. Numerous reports suggest relations between the expression of natural killer target structures and the differentiation stage of malignant cells. Effects of fagaronine on the expression of glycophorin A, transferrin receptor and CD15 antigen and susceptibility to NK-mediated lysis have been investigated in K562 cells and compared to those of two anthracyclines (Adriamycin and aclacinomycin A) known to be erythroid-differentiation inducers. When comparing the balance of differentiating effect and toxicity, the dose and time-dependent effects of the drugs, fagaronine and aclacinomycin, are equivalent on K562 cells. In experimental conditions where fagaronine (3500 nM), Adriamycin (40 nM) and aclacinomycin (15 nM) recruit the same percentage of hemoglobin-containing cells (40%-50%), glycophorin A expression increases and transferrin receptor expression decreases. Only Adriamycin treatment decreases CD15 antigen expression. In addition, Adriamycin and aclacinomycin, but not fagaronine, induce resistance to NK-mediated lysis. These data suggest that (a) it is unlikely that CD15 antigen and transferrin receptor, separately considered, can be unique target structures for NK cells; and (b) fagaronine is a potent erythroid inducer which, in our system, has similar effects to aclacinomycin without induced resistance to NK attack.