8-Methyltryptanthrin-Induced Differentiation of P19CL6 Embryonal Carcinoma Cells into Spontaneously Beating Cardiomyocyte-like Cells

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.

Phytochemical and biological research of Polygoneae medicinal resources

“…8-Methyltryptanthrin of P. tinctorium induced differentiation of P19CL6 embryonal carcinoma cells into spontaneously beating cardiomyocyte-like cells (Seya et al, 2014).…”

Identification of Spiro-Fused Pyrrolo[3,4-a]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation

“…Various biological activities have been found for indolo[2,1- b ]quinazolin-6,12-dione (tryptanthrin) and its analogues, e.g., anti-tumor [ 21 ], immune-modulatory [ 22 ], anti-inflammatory [ 23 ], antimicrobial [ 24 ], antileishmanial [ 25 ], antifungal [ 26 ], antimalarial [ 27 ], cytotoxic [ 28 ] and activity as indoleamine 2,3-dioxygenase (IDO-1) inhibitor [ 29 ] and antitubercular agent [ 30 ]. It was previously shown that 8-methyltryptanthrin successfully differentiated P19CL6 cells into spontaneously beating cardiomyocyte-like cells [ 31 ]. Liao and Leung found that tryptanthrin might cause growth inhibition of the human neuroblastoma LA-N-1 cells [ 32 ].…”

Platinum(ii) complexes with rutaecarpine and tryptanthrin derivatives induce apoptosis by inhibiting telomerase activity and disrupting mitochondrial function

“…1,7 Previous studies found that rutaecarpine and tryptanthrin derivatives exhibited diverse biological effects, such as antitumor, antimicrobial, and anti-inflammatory activities. [27][28][29][30][31][32][33][34][35] Recently, our group has reported that tryptanthrin derivatives and their Fe II and Co II complexes can specifically stabilize telomeric G4 DNA. However, there are only a few reported metal complexes containing rutaecarpine and tryptanthrin derivatives as c-myc G4 DNA ligands.…”