Effects of differentiation-inducing factors of Dictyostelium discoideum onhuman leukemia K562 cells: DIF-3 is the most potent anti-leukemic agent

DIF-1 (differentiation-inducing factor-1; 1-(3,5-dichloro-2,6-dihydroxy-4-m ethoxyphenyl)hexan-1-one) is a putative morphogen that induces stalk cell f ormation in the cellular slime mold, Dictyostelium discoideum. It has been previously reported that DIF-1 exhibits anti-tumor activity in mammalian ce lls. In this study, we examined the effects of six DIF analogues on DNA syn thesis, cell growth, erythroid differentiation, and cytosolic free calcium concentration ([Ca2+](i)) in human leukemia K562 cells. The DIF analogues u sed here were DIF-1, DIF-2 (which has pentanone in place of hexanone), DIF- 3 (dechlorinated form of DIF-1), 2-MIDIF-1 (2-methoxy isomer of DIF-1), DMP H (dechlorinated form of DIF-3), and THPH (4-hydroxy substitution of DMPH). DIF-3 proved to be the most potent anti-leukemic agent among them, and the order of potency for causing growth inhibition, erythroid induction, and i ncreases in [Ca2+](i) was established as DIF-3 > DIF-1 > DIF-2 > DMPH > 2-M IDIF-1 > THPH in all the categories tested. The present results suggest new routes for the development of more potent and effective anti-tumor agents. (C) 1999 Elsevier Science B.V. All rights reserved.