Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells

Cordycepin (3′-deoxyadenosin), a specific polyadenylation inhibitor, is the main functional component in Cordyceps militaris, one of the top three renowned traditional Chinese medicines. Cordycepin has been shown to possess many pharmacological activities including immunological stimulation, and ant...

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Bibliographic Details
Published in:Toxicology in vitro 2011-06, Vol.25 (4), p.817-824
Main Authors: Jeong, Jin-Woo, Jin, Cheng-Yun, Park, Cheol, Hong, Su Hyun, Kim, Gi-Young, Jeong, Yong Kee, Lee, Jae-Dong, Yoo, Young Hyun, Choi, Yung Hyun
Format: Article
Language:English
Subjects:
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - isolation & purification
Antineoplastic Agents - pharmacology
Antiviral agents
Apoptosis
Apoptosis - drug effects
Caspase
Caspases - drug effects
Caspases - metabolism
Cell Line, Tumor
Cordycepin
Cordyceps - chemistry
Deoxyadenosines - administration & dosage
Deoxyadenosines - isolation & purification
Deoxyadenosines - pharmacology
Dose-Response Relationship, Drug
Humans
Leukemia - drug therapy
Leukemia - pathology
Medicine, Chinese Traditional
Mitochondria - drug effects
Mitochondria - metabolism
Reactive Oxygen Species - metabolism
ROS
U937 Cells
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Summary:Cordycepin (3′-deoxyadenosin), a specific polyadenylation inhibitor, is the main functional component in Cordyceps militaris, one of the top three renowned traditional Chinese medicines. Cordycepin has been shown to possess many pharmacological activities including immunological stimulation, and anti-bacterial, anti-viral, and anti-tumor effects. However, the mechanisms underlying its anti-cancer mechanisms are not yet understood. In this study, the apoptotic effects of cordycepin were investigated in human leukemia cells. Treatment with cordycepin significantly inhibited cell growth in a concentration-dependent manner by inducing apoptosis but not necrosis. This induction was associated with generation of reactive oxygen species (ROS), mitochondrial dysfunction, activation of caspases, and cleavage of poly(ADP-ribose) polymerase protein. However, apoptosis induced by cordycepin was attenuated by caspase inhibitors, indicating an important role for caspases in cordycepin responses. Administration of N-acetyl- l-cysteine, a scavenger of ROS, also significantly inhibited cordycepin-induced apoptosis and activation of caspases. These results support a mechanism whereby cordycepin induces apoptosis of human leukemia cells through a signaling cascade involving a ROS-mediated caspase pathway.
ISSN:0887-2333
1879-3177
DOI:10.1016/j.tiv.2011.02.001