Analysis of induction of senescence-like growth arrest in glioblastoma cells by irradiation or arsenite.

Abstract

Arsenic is a potent anticancer agent for many human cancers. In this study, we try to investigate whether arsenite-induced DNA damage leads to p53-dependent premature senescence using human glioblastoma cells with p53-wild type (U87MG ) and p53 deficient (U87MG-E6). Arsenite dose-dependently reduced cell survival of both U87MG and U87MG-E6 cells. Low concentration of arsenite significantly induced DNA damage with increased gammaH2AX foci formation both in U87MG and U87MG-E6 cells. However, senescence was only induced by arsenite with significant SA-beta-gal staining cells and increased dimethyl- and trimethyl- lysine 9 of histone H3 (H3DMK9 and H3TMK9) foci formation accompanied by p21 accumulation in U87MG, but not in U87MG-E6 cells, suggesting that arsenite induces premature senescence as a result of DNA damage with heterochromatin formation through p53/p21 dependent pathway. Taken together, arsenite reduces cell survival via p53-independently and induces premature senescence via p53/p21-dependent pathway following DNA damage. This finding explored another new anti-tumor mechanisms induced by arsenite, which is an irreversible cell cycle arrest that limits.