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

Kim, Mun-Ock; Moon, Dong-Oh; Kang, Sang-Hyuck; Heo, Moon-Soo; Choi, Yung Hyun; Jung, Jee Hyung; Lee, Jae-Dong; Kim, Gi-Young

doi:10.1016/j.febslet.2008.08.030

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Volume 582, Issue 23 , Pages 3263-3269, 15 October 2008

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

Edited by Varda Rotter

Mun-Ock Kim
- Department of Microbiology, Pusan National University, Busan 609-735, Republic of Korea
Dong-Oh Moon
- Faculty of Applied Marine Science, Cheju National University, Jeju 690-756, Republic of Korea
Sang-Hyuck Kang
- Faculty of Applied Marine Science, Cheju National University, Jeju 690-756, Republic of Korea
Moon-Soo Heo
- Faculty of Applied Marine Science, Cheju National University, Jeju 690-756, Republic of Korea
Yung Hyun Choi
- Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-054, Republic of Korea
Jee Hyung Jung
- Department of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea
Jae-Dong Lee
- Department of Microbiology, Pusan National University, Busan 609-735, Republic of Korea
- Corresponding authors. Fax: +82 64 756 3493 (G.-Y. Kim), +82 51 510 2197 (J.-D. Lee).
Gi-Young Kim
- Faculty of Applied Marine Science, Cheju National University, Jeju 690-756, Republic of Korea
- Corresponding authors. Fax: +82 64 756 3493 (G.-Y. Kim), +82 51 510 2197 (J.-D. Lee).

Received 22 May 2008; received in revised form 11 August 2008; accepted 12 August 2008. published online 05 September 2008.

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 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.