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.
authors.affiliation: Department of Acupuncture & Moxibustion, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Kyung-Jun
authors.initials: KJ
authors.lastname: Jang
authors.affiliation: Department of Acupuncture & Moxibustion, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Gi-Sun
authors.initials: GS
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Department of Acupuncture & Moxibustion, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Cheol-Hong
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Acupuncture & Moxibustion, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Hyun-Min
authors.initials: HM
authors.lastname: Yoon
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.affiliation: School of Food Science and Technology, Chung-Ang University, Ansung 456-756, Republic of Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 361-804, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea; Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Republic of Korea. Electronic address: choiyh@deu.ac.kr.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D032661:Cordyceps / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
chemical_list: D000241:Adenosine; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D016271:Proto-Oncogene Proteins c-myc; D016329:Sp1 Transcription Factor; D019098:Telomerase; C489427:MYC protein, human; C108209:SP1 protein, human; C000599121:cordyceptin; C509186:TERT protein, human
keywords: Apoptosis; Cordycepin; Human telomerase reverse transcriptase; Phosphoinositide-3-kinase/Akt; Telomerase