Gossypol suppresses telomerase activity in human leukemia cells via regulating hTERT.
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.
Moon
Dong-Oh
DO
Faculty of Applied Marine Science, Cheju National University, Jeju 690-756, Republic of Korea.
Kim
Mun-Ock
MO
Choi
Yung Hyun
YH
Lee
Hee Gu
HG
Kim
Nam Deuk
ND
Kim
Gi-Young
GY
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
D003272:Contraceptive Agents, Male; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051057:Proto-Oncogene Proteins c-akt; D019098:Telomerase; D006072:Gossypol