pectenotoxin-2 and Leukemia

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.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Chromatin Immunoprecipitation; Furans; Gene Expression; Humans; Leukemia; Macrolides; Phosphorylation; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Pyrans; Sp1 Transcription Factor; Telomerase