title: Involvement of C/EBPβ in monocytic differentiation of acute myeloid leukemia cells induced by LW-218, a new synthesized flavonoid.
abstract: Our previous study investigated the effects of differentiation inducted by flavonoids derived from a Chinese herb. In this study, we found that LW-218, a new synthesized flavonoid, inhibited proliferation and induced differentiation of acute myeloid leukemia cells. The IC50s of LW-218 in HL-60, U937, K562, and NB4 cell lines were all less than 5 μM, suggesting greater capacity than compounds we have reported. LW-218 induced differentiation effects including morphologic changes, NBT reduction, and both of CD11b and CD14 expression. Results of western blots and siRNA transfection revealed that LW-218 increased the LAP/LIP ratio of C/EBPβ which regulated monocytic differentiation of leukemia cells. Meanwhile, these differentiation effects could be attenuated by silencing PLSCR1 via siRNA transfection. In addition, regulation on LAP/LIP ratio, of C/EBPβ was properly mediated by PLSCR1 which was up-regulated by LW-218. All these results suggested that C/EBPβ was involved in regulation of PKCδ/PLSCR1 pathway during flavonoids-induced differentiation. LW-218 was a prospective differentiation inductor of AML cells and was requisite to proceed further investigation.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Hui
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Guo
authors.forename: N
authors.initials: N
authors.lastname: Lu
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000032:analysis / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D009000:Monocytes / Q000166:cytology*; D049294:Phospholipid Transfer Proteins / Q000502:physiology; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D005419:Flavonoids; C000598094:LW-218; C493422:PLSCR1 protein, human; D049294:Phospholipid Transfer Proteins; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta