| Arsenite induces premature senescence via p53/p21 pathway as a result of DNA damage in
human malignant glioblastoma cells |
| Yasuharu Ninomiya1, Xing Cui2,*, Bing Wang1, Dong Yu3, Emiko Sekine-Suzuki4, Mitsuru Nenoi1 |
1Radiation Risk Reduction Research Program, Research Center for Radiation Protection and 2Medical Physics Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences,
3School of Radiological Medicine and Protection, Medical College of Soochow University,
4Research Center for Charged Particle Therapy, National Institute of Radiological Sciences |
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Abstract
Arsenite is a potent anticancer agent for many human cancers. 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). Arsenite dose-dependently reduced cell growth, and low concentration of arsenite significantly induced ャH2AX foci formation both in U87MG-neo and U87MG-E6 cells. However, senescence was induced by arsenite with senescence-associated モ-galactosidase staining and dimethyl- and trimethyl-lysine 9 of histone H3 (H3DMK9 and H3TMK9) foci formation accompanied by p21 accumulation only in U87MG-neo, suggesting that arsenite induces premature senescence as a result of DNA damage with heterochromatin formation through p53/p21 dependent pathway. Consistently, p21 and p53 siRNA decreased H3TMK9 foci formation in U87MG-neo treated with arsenite. Taken together, arsenite reduces cell growth p53-independently and induces premature senescence via p53/p21-dependent pathway following DNA damage. This finding explored new anti-tumor mechanisms induced by arsenite.
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| Abstract, Accepted Manuscript(in press) [Submitted on November 21, 2013, Accepted on January 26, 2014] |
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