MYELOID DIFFERENTIATION OF HL-60 CELLS INDUCED BY ANTITUMOR DRUG 3-NITROBENZOTHIAZOLO[3,2-A]QUINOLINIUM

Drugs which elicit cell differentiation might have an important role in the treatment of leukemias and other neoplasias. Various chemotherapeutic agents promote leukemic cell differentiation. The HL-60 cell line is a useful model to study in vitro myeloid differentiation. Sublethal concentrations of 3-nitrobenzothiazolo[3,2-a]quinolinium (NBQ), an antitopoisomerase II drug, were given to HL-60 cells from one to five days to evaluate its capacity to induce differentiation. NBQ-induced HL-60 cells reduced nitroblue tetrazolium (NBT), increased MY-4 receptors, increased phagocytic activity and displayed the granulocytic morphology. Flow cytometric DNA analysis of NBQ-induced cells revealed an arrest in the G1 phase a reduction in the relative percentage of cells in S and G2 + M phases. Our results suggest that NBQ induces an S-phase specific differentiation of HL-60 cells comparable to that previously described with dimethyl sulfoxide and retinoic acid. NBQ and its analogs, as differentiation inducers, may have potential utility as a novel therapeutic modality for leukemias.