Cordycepin induced eryptosis in mouse erythrocytes through a Ca2+-dependent pathway without caspase-3 activation.
Arch Toxicol
; 81(12): 859-65, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17541556
ABSTRACT
Cordyceps sinensis is a prized traditional Chinese medicine and its major component cordycepin is found to have anti-leukemia activities. However, its cytotoxicity in erythrocytes was unclear. To examine the effect of cordycepin on the induction of eryptosis (an apoptosis-like process in enucleated erythrocytes), flow cytometric assays based on membrane integrity and asymmetry were employed. For comparison, analyses were performed in parallel with two other anti-leukemia agents, indirubin 3'-monoxime (IDM) and As2O3. We found that at the IC50 against leukemia HL-60, cordycepin elicited eryptosis while IDM and As2O3 showed no erythrotoxicity in mouse erythrocytes. Mechanistically, cordycepin increased the [Ca2+]i and activated mu-calpain protease in a dose-dependent manner. Yet, no caspase-3 activation was observed in the cordycepin-treated erythrocytes. When extracellular Ca2+ was depleted, both the cordycepin-induced eryptosis and mu-calpain cleavage were suppressed. Our study therefore demonstrated for the first time that cordycepin induces eryptosis through a calcium-dependent pathway in the absence of mitochondria and caspase-3 activation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desoxiadenosinas
/
Cálcio
/
Apoptose
/
Eritrócitos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Arch Toxicol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
China