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http://dx.doi.org/10.5483/BMBRep.2014.47.10.254

Arsenite induces premature senescence via p53/p21 pathway as a result of DNA damage in human malignant glioblastoma cells  

Ninomiya, Yasuharu (Radiation Risk Reduction Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences)
Cui, Xing (Medical Physics Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences)
Yasuda, Takeshi (Radiation Emergency Medicine Research Program, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences)
Wang, Bing (Radiation Risk Reduction Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences)
Yu, Dong (School of Radiological Medicine and Protection, Medical College of Soochow University)
Sekine-Suzuki, Emiko (Research Program for Application of Heavy ions and Medical Science, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences)
Nenoi, Mitsuru (Radiation Risk Reduction Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences)
Publication Information
BMB Reports / v.47, no.10, 2014 , pp. 575-580 More about this Journal
Abstract
In this study, we investigate whether arsenite-induced DNA damage leads to p53-dependent premature senescence using human glioblastoma cells with p53-wild type (U87MG-neo) and p53 deficient (U87MG-E6). A dose dependent relationship between arsenite and reduced cell growth is demonstrated, as well as induced ${\gamma}H2AX$ foci formation in both U87MG-neo and U87MG-E6 cells at low concentrations of arsenite. Senescence was induced by arsenite with senescence-associated ${\beta}$-galactosidase staining. Dimethyl- and trimethyl-lysine 9 of histone H3 (H3DMK9 and H3TMK9) foci formation was accompanied by p21 accumulation only in U87MG-neo but not in U87MG-E6 cells. This suggests that arsenite induces premature senescence as a result of DNA damage with heterochromatin forming through a p53/p21 dependent pathway. p21 and p53 siRNA consistently decreased H3TMK9 foci formation in U87M G-neo but not in U87MG-E6 cells after arsenite treatment. Taken together, arsenite reduces cell growth independently of p53 and induces premature senescence via p53/p21-dependent pathway following DNA damage.
Keywords
Arsenite; Glioma; Heterochromatin formation; Premature senescence; p53;
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