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MARINE SPONGE EXTRACT PECTENOTOXIN-2 REPRESSES TELOMERASE ACTIVITY IN HUMAN LEUKEMIA CELLS THROUGH SUPPRESSION OF hTERT GENE EXPRESSION AND Akt-DEPENDENT hTERT PHOSPHORYLATION

Matharage Gayani Dilshara*, Ilandarage Menu Neelaka Molagoda, Rajapaksha Gedara Prasad Tharanga Jayasooriya, Yung Hyun Choi, Gi-Young Kim
 
Laboratory of Immunobiology,
Room no 5363,
School of  Biomedical Sciences 4,
Jeju National University,
66 Jejudaehakro,
Jeju Special Self-Governing Province 690 756,
Republic of Korea.
dilsharagm@gmail.com

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.

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