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

• Published in: Journal of bioscience and bioengineering 2015-03, Vol.119 (3), p.351-357
• Main Authors: Jang, Kyung-Jun, Kwon, Gi-Sun, Jeong, Jin-Woo, Kim, Cheol-Hong, Yoon, Hyun-Min, Kim, Gi-Young, Shim, Jung-Hyun, Moon, Sung-Kwon, Kim, Wun-Jae, Choi, Yung Hyun
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus - drug effects; Adenosine - analogs & derivatives; Adenosine - pharmacology; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell Proliferation - drug effects; Cordycepin; Cordyceps - chemistry; Down-Regulation - drug effects; Human telomerase reverse transcriptase; Humans; Leukemia - enzymology; Leukemia - genetics; Leukemia - pathology; Phosphatidylinositol 3-Kinases - metabolism; Phosphoinositide-3 Kinase Inhibitors; Phosphoinositide-3-kinase/Akt; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-myc - genetics; Signal Transduction - drug effects; Sp1 Transcription Factor - genetics; Telomerase; Telomerase - antagonists & inhibitors; Telomerase - biosynthesis; Telomerase - genetics; Telomerase - metabolism; Transcription, Genetic - drug effects; Transcription, Genetic - genetics
• ISSN: 1389-1723; 1347-4421
• DOI: 10.1016/j.jbiosc.2014.08.008

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.