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Cordyceptin induces apoptosis through repressing hTERT expression and inducing extranuclear export of hTERT

Paper ID Volume ID Publish Year Pages File Format Full-Text
20415 43173 2015 7 PDF Available
Title
Cordyceptin induces apoptosis through repressing hTERT expression and inducing extranuclear export of hTERT
Abstract

Cordycepin is an adenosine analog originally extracted from Cordyceps militaris that possesses many pharmacological effects including immune activation and antioxidant and antitumor effects. However, the underlying relationship between apoptosis and telomerase activity in response to cordycepin exposure has not been investigated. In this study, we found that cordycepin-induced apoptosis of human leukemia cells (H937 and THP-1 cells) was associated with inactivation of telomerase and downregulation of human telomerase reverse transcriptase (hTERT) as well as the transcription factors c-Myc and Sp1, which are required for basal transcription from the hTERT gene promoter. Cordycepin also attenuated the activation of phosphoinositide-3-kinase (PI3K)/Akt signaling, thereby reducing phosphorylation and nuclear translocation of hTERT. We further showed that the PI3K inhibitor LY29004 significantly decreased telomerase activity in cordycepin-treated cells and increased cordycepin-induced cell death. These findings demonstrate that cordycepin is cytotoxic to human leukemia cells and suppresses telomerase activity through transcriptional and post-translational suppression of hTERT by inactivating the PI3K/Akt signaling pathway.

Keywords
Cordycepin; Apoptosis; Telomerase; Human telomerase reverse transcriptase; Phosphoinositide-3-kinase/Akt
First Page Preview
Cordyceptin induces apoptosis through repressing hTERT expression and inducing extranuclear export of hTERT
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Bioscience and Bioengineering - Volume 119, Issue 3, March 2015, Pages 351–357
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering