SYNERGISTIC ACTION OF TIAZOFURIN AND RETINOIC ACID ON DIFFERENTIATION AND COLONY FORMATION OF HL-60 LEUKEMIA-CELLS

Tiazofurin and retinoic acid synergistically induced differentiation and inhibited colony formation in HL-60 human promyelocytic leukemia cells in cell culture. The synergism was the result of different mechanisms of action, since the effect of tiazofurin, unlike that of retinoic acid, was prevented by addition of guanosine. Since it has been shown that tiazofurin down-regulated the expression of c-Ki-ras oncogene, and retinoic acid that of the myc oncogene, the joint impact of these drugs is of clinical interest particularly in end-stage leukemia where the therapeutic usefulness of tiazofurin has recently been demonstrated (Tricot et al., Cancer Res. 47, 4988, 1987; Weber et al., Advan. Enzyme Regul. 27, 405, 1988; Tricot et al., Cancer Res. 49, 3696, 1989). © 1990.