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.
Kim
Mun-Ock
MO
Department of Microbiology, Pusan National University, Busan 609-735, Republic of Korea.
Moon
Dong-Oh
DO
Kang
Sang-Hyuck
SH
Heo
Moon-Soo
MS
Choi
Yung Hyun
YH
Jung
Jee Hyung
JH
Lee
Jae-Dong
JD
Kim
Gi-Young
GY
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D005663:Furans / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D018942:Macrolides; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D000095702:Polyether Toxins
D005663:Furans; D018942:Macrolides; D051057:Proto-Oncogene Proteins c-akt; D016271:Proto-Oncogene Proteins c-myc; D011714:Pyrans; D016329:Sp1 Transcription Factor; D019098:Telomerase; C098380:pectenotoxin 2; D000095702:Polyether Toxins