title: Effects of differentiation-inducing factors of Dictyostelium discoideum on human leukemia K562 cells: DIF-3 is the most potent anti-leukemic agent.
abstract: DIF-1 (differentiation-inducing factor-1; 1-(3,5-dichloro-2, 6-dihydroxy-4-methoxyphenyl)hexan-1-one) is a putative morphogen that induces stalk cell formation in the cellular slime mold, Dictyostelium discoideum. It has been previously reported that DIF-1 exhibits anti-tumor activity in mammalian cells. In this study, we examined the effects of six DIF analogues on DNA synthesis, cell growth, erythroid differentiation, and cytosolic free calcium concentration ([Ca2+]i) in human leukemia K562 cells. The DIF analogues used 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), DMPH (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 increases in [Ca2+]iTHPH in all the categories tested. The present results suggest new routes for the development of more potent and effective anti-tumor agents.
authors.affiliation: Department of Molecular Physiology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Showa-machi 3-39-15, Maebashi, Japan. kubohara@akagi.sb.gunma-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kubohara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004023:Dictyostelium / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006588:Hexanones / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007938:Leukemia / Q000473:pathology / Q000517:prevention & control; D010422:Pentanones / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D012118:Resorcinols / Q000494:pharmacology
chemical_list: C110391:(2,4,6-trihydroxyphenyl)-1-hexan-1-one; C400937:1-(3,5-dichloro-2,6-dihdyroxy-2-methoxyphenyl)hexan-1-one; D000970:Antineoplastic Agents; D006588:Hexanones; D010422:Pentanones; D010636:Phenols; D012118:Resorcinols; C053433:1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone; C055365:1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl-)-1-pentanone; C055364:1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone; D004247:DNA; D002118:Calcium