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

被引：20

作者：

Ninomiya, Yasuharu ^{[1
]}

Cui, Xing ^{[2
]}

Yasuda, Takeshi ^{[3
]}

Wang, Bing ^{[1
]}

Yu, Dong ^{[4
]}

Sekine-Suzuki, Emiko ^{[5
]}

Nenoi, Mitsuru ^{[1
]}

机构：

[1] Natl Inst Radiol Sci, Res Ctr Radiat Protect, Radiat Risk Reduct Res Program, Chiba 2638555, Japan

[2] Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Med Phys Res Program, Chiba 2638555, Japan

[3] Natl Inst Radiol Sci, Res Ctr Radiat Emergency Med, Radiat Emergency Med Res Program, Chiba 2638555, Japan

[4] Soochow Univ, Coll Med, Sch Radiol Med & Protect, Suzhou, Peoples R China

[5] Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Res Program Applicat Heavy Ions & Med Sci, Chiba 2638555, Japan

来源：

BMB REPORTS | 2014年 / 47卷 / 10期

关键词：

Arsenite; Glioma; Heterochromatin formation; Premature senescence; p53; CELLULAR SENESCENCE; IN-VIVO; HOMOLOGOUS RECOMBINATION; ACCELERATED SENESCENCE; PROMYELOCYTIC LEUKEMIA; MAMMALIAN-CELLS; STRAND BREAKS; UP-REGULATION; GLIOMA-CELLS; CANCER-CELLS;

D O I：

10.5483/BMBRep.2014.47.10.254

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：575 / 580

页数：6

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