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Butein suppresses c-Myc-dependent transcription and Akt-dependent phosphorylation of hTERT in human leukemia cells. Cancer letters [Cancer Lett] Journal article

 
TitleButein suppresses c-Myc-dependent transcription and Akt-dependent phosphorylation of hTERT in human leukemia cells.
Author(s)Moon DO, Kim MO, Lee JD, Choi YH, Kim GY 
InstitutionDepartment of Marine Life Science, Jeju National University and Jeju Regional Cancer Center, Jeju 690-756, Republic of Korea.
SourceCancer Lett 2009 Jun 26.
AbstractTelomerase, a ribonucleoprotein that plays an important role in neoplastic immortality, is up-regulated in approximately 85% of cancers, especially in leukemia. The polyphenol, butein, has potent effects against various types of cancer cells, but its effects on telomerase activity have not been well characterized. In this study, we show that butein causes a down-regulation of hTERT gene expression and a concomitant decrease of telomerase activity. Butein also suppresses expression of c-Myc at the transcriptional level and down-regulates DNA-binding activity, regardless of cell type specificity, in leukemia cells. DNA-binding activities of c-Myc to the hTERT core promoter were decreased in butein-treated cells, as seen by chromatin immunoprecipitation assay. Treatment with butein also suppressed the activation of Akt, thereby inhibiting hTERT phosphorylation and translocation into the nucleus. In this process, butein also up-regulated the surface expression of CD11b in leukemia cells. Inhibition of telomerase activity by butein was followed by loss of proliferative capacity, induction of apoptosis, and differentiation. These findings demonstrate the effectiveness of butein at inhibiting telomerase activity by down-regulating hTERT gene expression in human leukemia cells.
LanguageENG
Pub Type(s)JOURNAL ARTICLE
PubMed ID19560862
  
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