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 μ-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 μ-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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Abbreviations
- As2O3 :
-
Arsenic trioxide
- [Ca2+]i :
-
Intracellular free calcium concentration
- IDM:
-
Indirubin 3′-monoxime
- PE:
-
Phycoerythrin
- PS:
-
Phosphatidylserine
- RBC:
-
Red blood cell
- STS:
-
Staurosporine
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This work was supported by a direct grant from CUHK, earmarked grants from SHARF and Research Grants Council, Hong Kong, China.
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Lui, J.C.K., Wong, J.W.Y., Suen, Y.K. et al. Cordycepin induced eryptosis in mouse erythrocytes through a Ca2+-dependent pathway without caspase-3 activation. Arch Toxicol 81, 859–865 (2007). https://doi.org/10.1007/s00204-007-0214-5
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DOI: https://doi.org/10.1007/s00204-007-0214-5