Most of the literature shows that Doxorubicin treatment to cancer cells cause a cell cycle arrest in either G1 or G2/M phase. But in my case treating MDA-MB-231 with a Dox nanoparticle caused cell cycle arrest at S phase. And by western blot analysis we found p53 upregulation in treated cells. Can p53 accumulation cause S phase cell cycle arrest? What can be the possible explanation?
The cells show an increase in accumulation of p53 protein that is maximal at 24 h after drug exposure. Increased p53 levels can be induced in cells by DNA-damaging agents; however, using alkaline elution and sister chromatid exchange assays we detect no DNA damage induced by geldanamycin. Using dominant negative mutant TP53 transfectants of A2780 we have analysed the possible dependence of geldanamycin-induced cell-cycle arrests on the presence of functional p53. We observe no difference in cell-cycle arrests in mutant p53 transfectants known to have the p53-DNA damage-response pathway inactivated as compared with vector-alone controls. Similarly, we observe no difference in clonogenic resistance to the cytotoxicity of geldanamycin in these cells. These results suggest that geldanamycin can induce increased p53 protein by a mechanism not involving DNA damage. Furthermore, the cell-cycle arrests and cytotoxic effects of geldanamycin in these cells are not mediated by p53-dependent pathways.
Article Cell-cycle arrest and p53 accumulation induced by geldanamyc...
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