Pectenotoxin‐2 represses telomerase activity in human leukemia cells through suppression of hTERT gene expression and Akt‐dependent hTERT phosphorylation

Abstract

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 cMyc 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.

Pectenotoxin-2 from Marine Sponges: A Potential Anti-Cancer Agent—A Review

“…According to our findings, PTX-2 suppressed telomerase activity in human leukemia cells via the transcriptional downregulation of hTERT through reductions in c-Myc and Sp1 activities [42]. Akt1 is involved in cellular survival pathways by inhibiting apoptotic processes.…”

“…Akt phosphorylation can also be a potent inducer of telomerase activation via hTERT phosphorylation linked to nuclear localization. Our previous data indicated that PTX-2 downregulated p-Akt and the phosphorylation and translocation of hTERT [42]. Thus PTX-2 treatment regulates hTERT at the post-translational level by downregulating its phosphorylation by the Akt pathway [43].…”

Pectenotoxin-2 induces G2/M phase cell cycle arrest in human breast cancer cells via ATM and Chk1/2-mediated phosphorylation of cdc25C

“…Previous studies have shown that PTX-2 displays selective and potent cytotoxicity against various types of cancer cells (3). More recently, we reported that PTX-2 can induce apoptosis in leukemia cells, with concomitant attenuation of telomerase activity (20) and NF-κB binding activity (21). However, we still do not know the mechanisms by which PTX-2 inhibits proliferation of cancer cells, because little is known about PTX-2-induced G 2 /M arrest.…”

The impact of cellular senescence in cancer therapy: is it true or not?

“…Several compounds such as BIBR1532{2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-benzoic acid} [22], TNQX (2, 3, 7-trichloro-5-nitroquinoxaline) [23,24] have been reported to possess these properties. Protein kinase C (PKC) and Akt have been shown to phosphorylate hTERT and to enhance the telomerase activity [25]. Therefore, it is conceivable that the inhibitors of these protein kinases should have inhibitory effects on telomerase activity.…”