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Cepharanthine induces apoptosis through the mitochondria/caspase pathway in murine dendritic cells
Tomofumi Uto1,2, Masaaki Toyama1, Keisuke Yoshinaga3
1a Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases , Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima , Japan ;
Context:
Cepharanthine (CEP) is a biscoclaurine amphipathic alkaloid isolated from the plant Stephania cepharantha Hayata. Although the effects of CEP on several types of cells have been investigated, those on dendritic cells (DCs) are poorly understood.
Objective:
To investigate the effect of CEP on the induction of apoptosis in murine DCs.
Materials And Methods:
The induction of Annexin V/propidium iodide-positive cells and permeability of mitochondrial membrane potential were evaluated in DCs treated with CEP. Cell-associated caspase activity and DNA fragmentation were analyzed by Dual Sensor: MitoCasp™ and agarose gel electrophoresis, respectively.
Results:
The number of dead cells was increased by CEP treatment at concentrations more than 10 μg/ml. Flow cytometric analysis revealed that the cell death was found to be apoptosis, CEP treatment reduced mitochondrial membrane potential and upregulated the level of cleaved caspases, including caspase-9 and caspase-3/7, in a dose-dependent fashion. Furthermore, DNA fragmentation was observed in CEP-treated DCs.
Conclusion:
CEP is capable of inducing apoptosis and may be a potential agent against DC-mediated and allergic diseases.
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