RRC ID 45105
Author Seya K, Yamaya A, Kamachi S, Murakami M, Kitahara H, Kawakami J, Okumura K, Murakami M, Motomura S, Furukawa K.
Title 8-Methyltryptanthrin-induced differentiation of P19CL6 embryonal carcinoma cells into spontaneously beating cardiomyocyte-like cells.
Journal J Nat Prod
Abstract Enhancement of cardiac differentiation is critical to stem cell transplantation therapy for severe ischemic heart disease. The aim of this study was to investigate whether several derivatives of tryptanthrin (1), extracted from the medicinal plant Polygonum tinctorium, induce the differentiation of P19CL6 mouse embryonal carcinoma cells into beating cardiomyocyte-like cells. P19CL6 cells were cultured in α-MEM supplemented with 10% FBS including a test compound or vehicle. Drug-induced differentiation was assessed by measuring the number of beating and nonbeating aggregates and the area of beating aggregates, and the expression of genes involved in cardiac differentiation was evaluated by real-time PCR. A 1 μM concentration of 8-methyltryptanthrin (2) induced the differentiation of P19CL6 cells into cardiomyocyte-like cells to a significantly greater degree than 1% dimethyl sulfoxide (DMSO), a conventional differentiation inducer of P19CL6 cells. Furthermore, 2 strongly increased both the number and the area of spontaneously beating aggregates in comparison with DMSO. Two distinct genes of the calcium channel family, Cav1.2 and Cav3.1, underlying cardiac automaticity were significantly expressed in the presence of 2. Gap junction genes GJA1 and GJA5 contributing to the synchronized contraction of the myocardium were also induced significantly by 2. These results suggest that 2 successfully differentiated P19CL6 cells into spontaneously beating cardiomyocyte-like cells by activating the gene expression of pacemaker channels and gap junctions.
Volume 77(6)
Pages 1413-9
Published 2014-6-27
DOI 10.1021/np500108r
PMID 24885014
MeSH Animals Cell Differentiation / drug effects Dimethyl Sulfoxide / pharmacology Embryonal Carcinoma Stem Cells Mice Molecular Structure Myocardium / cytology Myocytes, Cardiac / cytology Myocytes, Cardiac / drug effects* Organic Chemicals Plants, Medicinal / chemistry* Polygonum / chemistry* Polymerase Chain Reaction Quinazolines / chemistry Quinazolines / isolation & purification Quinazolines / pharmacology*
IF 3.782
Times Cited 12
Human and Animal Cells P19CL6