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

Ying Chen; Shih-Hung Yang; Dueng-Yuan Hueng; Jhih-Pu Syu; Chih-Chen Liao; Ya-Chieh Wu

doi:10.1016/j.cbi.2014.03.010

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

Chem Biol Interact. 2014 Jun 5:216:17-25. doi: 10.1016/j.cbi.2014.03.010. Epub 2014 Apr 2.

Authors

Ying Chen¹, Shih-Hung Yang², Dueng-Yuan Hueng³, Jhih-Pu Syu⁴, Chih-Chen Liao⁴, Ya-Chieh Wu⁵

Affiliations

¹ Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address: ychen0523@ndmctsgh.edu.tw.
² Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taiwan.
³ Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁴ Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taiwan.
⁵ Department of Nursing, Ching Kuo Institute of Management and Health, Keelung, Taiwan.

PMID: 24704558
DOI: 10.1016/j.cbi.2014.03.010

Abstract

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.

Keywords: Adenosine 2A receptor; Apoptosis; Cordycepin; Glioma; p53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Apoptosis / drug effects*
Caspase 7 / genetics
Caspase 7 / metabolism*
Cell Line, Tumor
Cell Survival
Deoxyadenosines / pharmacology*
Gene Expression Regulation, Neoplastic / drug effects
Glioma / drug therapy*
Poly(ADP-ribose) Polymerases / genetics
Poly(ADP-ribose) Polymerases / metabolism
RNA Interference
RNA, Small Interfering
Rats
Receptors, Adenosine A2 / genetics
Receptors, Adenosine A2 / metabolism*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*

Substances

Antineoplastic Agents
Deoxyadenosines
RNA, Small Interfering
Receptors, Adenosine A2
Tumor Suppressor Protein p53
Poly(ADP-ribose) Polymerases
Caspase 7
cordycepin