Differentiation of Mouse and Human Myeloid Leukemia Cells Induced by an Antitumor Antibiotic, Ascofuranone

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Mouse myeloid leukemia cells, Ml, were induced to differentiate into phagocytes by treatment with ascofuranone (AF). AF also induced differentiation of human promyelocytic leukemia HL60 cells and human erythroid leukemia K562 cells into granulocytes and erythrocytes, as detected by nitroblue tetrazolium reducing activity and benzidine staining, respectively.
The antibiotic enhanced acetate incorporation of K562 cells. The increase was not observed with the cells of HL60 and two human B lymphoma lines, Daudi and Raji. The increase was diminished by the addition of a glycolysis inhibitor, deoxyglucose. Inhibitors of respiration, antimycin and sodium azide, also enhanced acetate incorporation of K562 cells specifically, which was diminished by the addition of deoxyglucose. Furthermore, antimycin induced differentiation of K562 and HL60 cells. These results suggest a possible relationship between cell differentiation and inhibition of respiration.