title: Identification and characterization of CW108F, a novel β-carboline compound that promotes cardiomyogenesis of stem cells.
abstract: OBJECTIVE
  The aim of this study was to identify new compounds that induce cardiomyocyte differentiation of stem cells through cell-based screening and investigate lineage specificity and mechanisms in vitro.
  
  
  METHODS
  Embryoid bodies (EBs) formed from TC-1/KH2 mouse embryonic stem cells (ESCs) carrying the gene for enhanced green fluorescent protein (EGFP) under the control of the α-myosin heavy chain (MHC) promoter were treated with test compounds. The number of cardiomyocyte-like (EGFP-expressing) cells in EBs was determined by fluorescence-activated cell sorting. Cardiomyocyte differentiation was further confirmed using lineage-specific biochemical assays and by investigating the expression of cardiomyocyte-specific and "stemness"-associated genes. Nuclear factor-kappaB (NF-κB) signaling activity was measured in A549 cells using a reporter-gene assay.
  
  
  RESULTS
  A β-carboline compound, designated CW108F, increased the number of mouse ESCs expressing α-MHC promoter-driven EGFP and the proportion of beating EBs. CW108F also increased expression of MHC in P19 stem cells, but did not induce osteogenesis of MC3T3-E1 cells, suggesting lineage-specific activity toward cardiomyocytes. CW108F upregulated expression of cardiac-specific GATA-4 and atrial natriuretic factor (ANF) genes in TC-1/KH2 cells, but downregulated expression of the stemness genes, Oct-4 and brachyury. CW108F inhibited NF-κB transcriptional activity, an effect that might contribute to its cardiomyogenesis-promoting activity.
  
  
  CONCLUSIONS
  The results of this study suggest that the novel β-carboline, CW108F, promotes the differentiation of ESCs into cardiomyocytes and may be useful for investigating molecular pathways of cardiomyogenesis and generating cardiomyocytes from ESCs.
authors.affiliation: Central Research Institute, JW Pharmaceutical Corporation, Hwaseong-City, Gyeonggi-Do 445-380, Republic of Korea.
authors.forename: Se-Woong
authors.initials: SW
authors.lastname: Oh
authors.forename: Bora
authors.initials: B
authors.lastname: Kim
authors.forename: Sejin
authors.initials: S
authors.lastname: Jeon
authors.forename: Du-Min
authors.initials: DM
authors.lastname: Go
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Kyoung
authors.initials: K
authors.lastname: Baek
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Kim
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D058732:Embryoid Bodies / Q000166:cytology / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: C584023:CW108F; D002243:Carbolines; D016328:NF-kappa B; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018995:Myosin Heavy Chains
keywords: Cardiomyogenesis; Differentiation; Stem cells; β-carboline chemical