Cordycepin induces apoptosis of C6 glioma cells through the adenosine 2A receptor-p53-caspase-7-PARP pathway*

被引:49
作者
Chen, Ying [1 ]
Yang, Shih-Hung [2 ]
Hueng, Dueng-Yuan [3 ]
Syu, Jhih-Pu [4 ]
Liao, Chih-Chen [4 ]
Wu, Ya-Chieh [5 ]
机构
[1] Natl Def Med Ctr, Dept Biol & Anat, Taipei, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Surg, Div Neurosurg, Taipei, Taiwan
[3] Natl Def Med Ctr, Dept Neurol Surg, Triserv Gen Hosp, Taipei, Taiwan
[4] Natl Taiwan Univ, Coll Med, Dept Anat & Cell Biol, Taipei, Taiwan
[5] Ching Kuo Inst Management & Hlth, Dept Nursing, Keelung, Taiwan
关键词
Cordycepin; Apoptosis; Glioma; Adenosine 2A receptor; p53; CARCINOMA CELLS; MOUSE MELANOMA; P53; 3'-DEOXYADENOSINE; EXPRESSION; PHOSPHORYLATION; POLYADENYLATION; RECEPTORS; INDUCTION; GROWTH;
D O I
10.1016/j.cbi.2014.03.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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. (c) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:17 / 25
页数:9
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