title: Induction of Nuclear Enlargement and Senescence by Sirtuin Inhibitors in Glioblastoma Cells.
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.
authors.affiliation: College of Pharmacy and Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea.
authors.forename: Kyoung B
authors.initials: KB
authors.lastname: Yoon
authors.affiliation: College of Pharmacy and Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea.
authors.forename: Kyeong R
authors.initials: KR
authors.lastname: Park
authors.affiliation: Division of Basic Science, Research Institute, National Cancer Center, Goyang 10408, Korea.
authors.forename: Soo Y
authors.initials: SY
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Han
keywords: EX527; Senescence; Sirtuin; Tenovin-1