Y. Kubohara, Effects of differentiation-inducing factors of Dictyostelium discoideum onhuman leukemia K562 cells: DIF-3 is the most potent anti-leukemic agent, EUR J PHARM, 381(1), 1999, pp. 57-62
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.