Histone deacetylase inhibitor AR42 regulates telomerase activity in human glioma cells via an Akt-dependent mechanism

Ya Luen Yang, Po Hsien Huang, Hao Chieh Chiu, Samuel K. Kulp, Ching Shih Chen, Cheng Ju Kuo, Huan Da Chen, Chang Shi Chen

研究成果: Article同行評審

18 引文 斯高帕斯(Scopus)

摘要

Epigenetic regulation via abnormal activation of histone deacetylases (HDACs) is a mechanism that leads to cancer initiation and promotion. Activation of HDACs results in transcriptional upregulation of human telomerase reverse transcriptase (hTERT) and increases telomerase activity during cellular immortalization and tumorigenesis. However, the effects of HDAC inhibitors on the transcription of hTERT vary in different cancer cells. Here, we studied the effects of a novel HDAC inhibitor, AR42, on telomerase activity in a PTEN-null U87MG glioma cell line. AR42 increased hTERT mRNA in U87MG glioma cells, but suppressed total telomerase activity in a dose-dependent manner. Further analyses suggested that AR42 decreases the phosphorylation of hTERT via an Akt-dependent mechanism. Suppression of Akt phosphorylation and telomerase activity was also observed with PI3K inhibitor LY294002 further supporting the hypothesis that Akt signaling is involved in suppression of AR42-induced inhibition of telomerase activity. Finally, ectopic expression of a constitutive active form of Akt restored telomerase activity in AR42-treated cells. Taken together, our results demonstrate that the novel HDAC inhibitor AR42 can suppress telomerase activity by inhibiting Akt-mediated hTERT phosphorylation, indicating that the PI3K/Akt pathway plays an important role in the regulation of telomerase activity in response to this HDAC inhibitor.

原文English
頁(從 - 到)107-112
頁數6
期刊Biochemical and Biophysical Research Communications
435
發行號1
DOIs
出版狀態Published - 2013 5月 24

All Science Journal Classification (ASJC) codes

  • 生物物理學
  • 生物化學
  • 分子生物學
  • 細胞生物學

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