RRC ID |
45105
|
著者 |
Seya K, Yamaya A, Kamachi S, Murakami M, Kitahara H, Kawakami J, Okumura K, Murakami M, Motomura S, Furukawa K.
|
タイトル |
8-Methyltryptanthrin-induced differentiation of P19CL6 embryonal carcinoma cells into spontaneously beating cardiomyocyte-like cells.
|
ジャーナル |
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.
|
巻・号 |
77(6)
|
ページ |
1413-9
|
公開日 |
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
|
引用数 |
12
|
WOS 分野
|
PLANT SCIENCES
PHARMACOLOGY & PHARMACY
CHEMISTRY, MEDICINAL
|
リソース情報 |
ヒト・動物細胞 |
P19CL6 |