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8‑Methyltryptanthrin-Induced Differentiation of P19CL6 Embryonal Carcinoma Cells into Spontaneously Beating Cardiomyocyte-like Cells
journal contribution
posted on 2014-06-27, 00:00 authored by Kazuhiko Seya, Asako Yamaya, Sayuri Kamachi, Mana Murakami, Haruo Kitahara, Jun Kawakami, Ken Okumura, Manabu Murakami, Shigeru Motomura, Ken-Ichi FurukawaEnhancement 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.
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pacemaker channelsnonbeating aggregatesischemic heart diseasecell transplantation therapyP 19CL mouse embryonal carcinoma cellsPCRtest compoundP 19CL Embryonal Carcinoma Cellsgene expression1 μ M concentrationcalcium channel familydifferentiation inducerCav 1.22. Gap junction genes GJA 1FBSplant Polygonum tinctoriumgap junctionsMEMP 19CL cellsGJA 5DMSO
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