Cordycepin induces apoptosis of C6 glioma cells through the adenosine 2A receptor-p53-caspase-7-PARP pathway
Journal
Chemico-Biological Interactions
Journal Volume
216
Journal Issue
1
Pages
17-25
Date Issued
2014
Author(s)
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. ? 2014 Elsevier Ireland Ltd. All rights reserved.
SDGs
Other Subjects
adenosine A2 receptor; caspase 3; caspase 7; cordycepin; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein p53; small interfering RNA; animal cell; apoptosis; article; astrocyte; cell survival; cell viability; concentration response; controlled study; glioma cell; nonhuman; protein cleavage; protein phosphorylation; rat; signal transduction; Adenosine 2A receptor; Apoptosis; Cordycepin; Glioma; p53; Animals; Antineoplastic Agents; Apoptosis; Caspase 7; Cell Line, Tumor; Cell Survival; Deoxyadenosines; Gene Expression Regulation, Neoplastic; Glioma; Poly(ADP-ribose) Polymerases; Rats; Receptors, Adenosine A2; RNA Interference; RNA, Small Interfering; Tumor Suppressor Protein p53
Publisher
Elsevier Ireland Ltd
Type
journal article