title: Ganglioside GM3 is required for caffeic acid phenethyl ester-induced megakaryocytic differentiation of human chronic myelogenous leukemia K562 cells.
abstract: The human chronic myelogenous cell line K562 has been used extensively as a model for the study of leukemia differentiation. We show here that treatment of K562 cells with caffeic acid phenethyl ester (CAPE) induced a majority of cells to differentiate towards the megakaryocytic lineage. Microscopy analysis showed that K562 cells treated with CAPE exhibited characteristic features of physiological megakaryocytic differentiation, including the presence of vacuoles and demarcation membranes. Differentiation of K562 cells treated with CAPE was also accompanied by a net increase in megakaryocytic markers. The transcriptional activity of lactosylceramide α-2,3-sialyltransferase (GM3 synthase) and synthesis of ganglioside GM3 were increased by CAPE treatment. The promoter analysis of GM3 synthase demonstrated that CAPE induced the expression of GM3 synthase mRNA via activation of the cAMP response element-binding protein (CREB), transcription factor in nucleus. Interestingly, the inhibition of ganglioside GM3 synthesis by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propranol (D-PDMP) and GM3 synthase-siRNA blocked the CAPE-induced expression of the megakaryocytic markers and differentiation of K562 cells. Taken together, these results suggest that CAPE induces ganglioside GM3-mediated megakaryocytic differentiation of human chronic myelogenous cells.
authors.affiliation: a Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sungkyunkwan University, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea.
authors.forename: Un-Ho
authors.initials: UH
authors.lastname: Jin
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chung
authors.forename: Kwon-Ho
authors.initials: KH
authors.lastname: Song
authors.forename: Choong-Hwan
authors.initials: CH
authors.lastname: Kwak
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D005679:G(M3) Ganglioside / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D008533:Megakaryocytes / Q000502:physiology*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D005679:G(M3) Ganglioside; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: CREB; cAMP response element-binding protein; caffeic acid phenethyl ester; différenciation en mégacaryocytes; ganglioside GM3; megakaryocytic differentiation; phénylester d’acide caféique