Studies of the differentiation properties of camptothecin in the human leukaemic cells K562.

Camptothecin, a specific inhibitor of topoisomerase I, caused erythroid differentiation of the human leukaemia cell-line K562, as assessed by benzidine staining at 70 h recovery following a 60 min treatment of the cells. Differentiation was confirmed by increased levels of epsilon-globin and gamma-globin mRNA in the treated cells and was accompanied by down-regulation of c-myb mRNA. Synchronisation of K562 cells by non-cytotoxic doses of methotrexate increased the differentiation induced by camptothecin, without affecting the camptothecin-induced inhibition of cellular proliferation. Camptothecin induction of differentiation and inhibition of proliferation may occur by independent mechanisms.