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Induction of Nuclear Enlargement and Senescence by Sirtuin Inhibitors in Glioblastoma Cells

  • Kyoung B. Yoon (College of Pharmacy and Research Institute of Life Sciences, Gyeongsang National University) ;
  • Kyeong R. Park (College of Pharmacy and Research Institute of Life Sciences, Gyeongsang National University) ;
  • Soo Y. Kim (Division of Basic Science, Research Institute, National Cancer Center) ;
  • Sun-Young Han (College of Pharmacy and Research Institute of Life Sciences, Gyeongsang National University)
  • Received : 2016.03.11
  • Accepted : 2016.05.20
  • Published : 2016.06.30
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Abstract

Sirtuin family members with lysine deacetylase activity are known to play an important role in anti-aging and longevity. Cellular senescence is one of the hallmarks of aging, and downregulation of sirtuin is reported to induce premature senescence. In this study, we investigated the effects of small-molecule sirtuin inhibitors on cellular senescence. Various small molecules such as tenovin-1 and EX527 were employed for direct sirtuin activity inhibition. U251, SNB-75, and U87MG glioblastoma cells treated with sirtuin inhibitors exhibited phenotypes with nuclear enlargement. Furthermore, treatment of rat primary astrocytes with tenovin-1 also increased the size of the nucleus. The activity of senescence-associated β-galactosidase, a marker of cellular senescence, was induced by tenovin-1 and EX527 treatment in U87MG glioblastoma cells. Consistent with the senescent phenotype, treatment with tenovin-1 increased p53 expression in U87MG cells. This study demonstrated the senescence-inducing effect of sirtuin inhibitors, which are potentially useful tools for senescence research.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A2A01053928), and by the Gyeongsang National University Fund for Professors on Sabbatical leave, 2016.

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