title: Gossypol suppresses telomerase activity in human leukemia cells via regulating hTERT.
abstract: Gossypol is a polyphenolic compound originally isolated from cottonseed that has long been used successfully as a contraceptive drug for males. However, the molecular mechanism of anti-telomerase effects of gossypol is not entirely understood. In this study, we observed direct cytotoxicity and inhibition of telomerase activity with downregulation of telomerase reverse transcriptase (hTERT) expression. Gossypol treatment resulted in a decrease of c-Myc expression and binding activity. Gossypol treatment also suppressed the activation of Akt, thereby inhibiting hTERT phosphorylation and translocation into the nucleus. We conclude that gossypol regulates the loss of telomerase activity through transcriptional and posttranslational modifications of hTERT.
authors.affiliation: Faculty of Applied Marine Science, Cheju National University, Jeju 690-756, Republic of Korea.
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Mun-Ock
authors.initials: MO
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Hee Gu
authors.initials: HG
authors.lastname: Lee
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D003272:Contraceptive Agents, Male; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051057:Proto-Oncogene Proteins c-akt; D019098:Telomerase; D006072:Gossypol