Cordycepin induces apoptosis of C6 glioma cells through the adenosine 2A receptor-p53-caspase-7-PARP pathway.
Cordycepin, 3'-deoxyadenosine from Cordyceps sinensis, has been shown to exert anti-tumor effects in several cancer cell lines. This study investigated the effect of cordycepin on a rat glioma cell line. Cordycepin caused apoptosis in C6 glioma cells in a time- and concentration-dependent manner, but did not affect the survival of primary cultured rat astrocytes. Cordycepin increased the total protein levels of p53 and phosphorylated p53 in the C6 cells. Levels of cleaved caspase-7 and poly (ADP-ribose) polymerase (PARP), but not cleaved caspase-3, were also increased after cordycepin treatment. Specific inhibitors for p53 and caspases abrogated cordycepin-induced caspase-7 and PARP cleavage, and prevented cordycepin-induced apoptosis. Moreover, siRNA knockdown of p53 blocked cordycepin-induced cleavage of caspase-7 and PARP. Both adenosine 2A receptor (A2AR) antagonist and small interference RNA (siRNA) knockdown of A2AR blocked cordycepin-induced apoptosis, p53 activation, and caspase-7 and PARP cleavage. These may provide a new strategy of cordycepin for glioma therapy in the future.
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address: ychen0523@ndmctsgh.edu.tw.
Ying
Y
Chen
Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taiwan.
Shih-Hung
SH
Yang
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Dueng-Yuan
DY
Hueng
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taiwan.
Jhih-Pu
JP
Syu
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taiwan.
Chih-Chen
CC
Liao
Department of Nursing, Ching Kuo Institute of Management and Health, Keelung, Taiwan.
Ya-Chieh
YC
Wu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003839:Deoxyadenosines / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D043683:Receptors, Adenosine A2 / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D034741:RNA, Small Interfering; D043683:Receptors, Adenosine A2; D016159:Tumor Suppressor Protein p53; D011065:Poly(ADP-ribose) Polymerases; D053179:Caspase 7; C058120:cordycepin
Adenosine 2A receptor; Apoptosis; Cordycepin; Glioma; p53