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KMID : 0624620140470100575
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BMB Reports
2014 Volume.47 No. 10 p.575 ~ p.580
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Arsenite induces premature senescence via p53/p21 pathway as a result of DNA damage in human malignant glioblastoma cells
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Ninomiya Yasuharu
Cui Xing
Yasuda Takeshi
Wang Bing
Yu Dong
Sekine-Suzuki Emiko
Nenoi Mitsuru
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Abstract
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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 γH2AX foci formation in both U87MG-neo and U87MG-E6 cells at low concentrations of arsenite. Senescence was induced by arsenite with senescence-associated β-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.
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KEYWORD
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Arsenite, Glioma, Heterochromatin formation, Premature senescence, p53
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