Identification and characterization of CW108F, a Novel β-carboline compound that promotes cardiomyogenesis of stem cells

Se Woong Oh, Bora Kim, Sejin Jeon, Du Min Go, Min Kyoung Kim, Kyoung Baek, Goo Taeg Oh, Dae Yong Kim

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Aims 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. Main 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. Key findings 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. Significance 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.

Original languageEnglish
Pages (from-to)409-415
Number of pages7
JournalLife Sciences
Volume93
Issue number9-11
DOIs
StatePublished - 17 Sep 2013

Keywords

  • β-carboline chemical
  • Cardiomyogenesis
  • Differentiation
  • Stem cells

Fingerprint

Dive into the research topics of 'Identification and characterization of CW108F, a Novel β-carboline compound that promotes cardiomyogenesis of stem cells'. Together they form a unique fingerprint.

Cite this