Cepharanthine induces apoptosis through the mitochondria/caspase pathway in murine dendritic cells.
BACKGROUND
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.


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.


CONCLUSIONS
CEP is capable of inducing apoptosis and may be a potential agent against DC-mediated and allergic diseases.
a Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases , Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima , Japan ;|b The Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST) , Tokyo , Japan ;
Tomofumi
T
Uto
a Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases , Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima , Japan ;
Masaaki
M
Toyama
c Department of Biological and Chemical Systems Engineering , National Institute of Technology, Kumamoto College , Yatsushiro , Japan.
Keisuke
K
Yoshinaga
a Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases , Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima , Japan ;|b The Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST) , Tokyo , Japan ;
Masanori
M
Baba
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D020169:Caspases / Q000276:immunology*; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000276:immunology*; D052117:Benzodioxoles
D044182:Benzylisoquinolines; D020169:Caspases; C006947:cepharanthine; D052117:Benzodioxoles
Apoptosis; cepharanthine; dendritic cells; immunotherapeutics; plant alkaloid