Pectenotoxin-2 represses telomerase activity in human leukemia cells through suppression of hTERT gene expression and Akt-dependent hTERT phosphorylation.
In this study, we found that pectenotoxin-2 (PTX-2) decreased cell viability and inhibited telomerase activity with downregulation of hTERT expression in human leukemia cells. PTX-2 treatment also reduced c-Myc and Sp1 gene expression and DNA binding activity. Further chromatin immunoprecipitation assay demonstrated that PTX-2 attenuated the binding of c-Myc and ... Sp1 to the regulatory regions of hTERT. We also observed that PTX-2 treatment attenuated the phosphorylation of Akt, thereby reducing the phosphorylation and nuclear translocation of hTERT. We concluded that PTX-2 suppressed telomerase activity through the transcriptional and post-translational suppression of hTERT and this process precedes cellular differentiation of human leukemia cells.
Mesh Terms:
Apoptosis, Cell Line, Tumor, Cell Proliferation, Chromatin Immunoprecipitation, Furans, Gene Expression, Humans, Leukemia, Phosphorylation, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-myc, Pyrans, Sp1 Transcription Factor, Telomerase
Apoptosis, Cell Line, Tumor, Cell Proliferation, Chromatin Immunoprecipitation, Furans, Gene Expression, Humans, Leukemia, Phosphorylation, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-myc, Pyrans, Sp1 Transcription Factor, Telomerase
FEBS Lett.
Date: Oct. 15, 2008
PubMed ID: 18775701
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