Abstract
Abstract Several studies over the past decade have shown that regular use of aspirin reduces the risk of cancers of various organs such as colon, breast, lung and prostate tissue. The mechanism by which aspirin exerts its anti-cancer effects is not clearly understood. Previous studies from our laboratory showed that aspirin acetylates the tumor suppressor protein p53 and modulates target gene expression in MDA-MB-231 breast cancer cells. We now have extended these studies to include HCT116 (wt-type p53) and HT-29 (mutant p53) colon cancer cells. Using anti-acetyl p53 antibody, we show in the present study that aspirin acetylated p53 at lysine 382 in both cell types. It also detected two other proteins of size 63 kDA and 35 kDa, which are likely to represent other isoforms of p53. Aspirin also acetylated recombinant p53 (rp53) in vitro, suggesting that the mechanism of cellular acetylation may be through a direct non-enzymatic chemical reaction. Mass spectrometry analysis of the aspirin-treated rp53 identified 7 acetylate lysine residues. In HCT116 and HT-29 cells, aspirin-induced acetylation of p53 was observed in a concentration dependent manner. The acetylated p53 was localized to the nucleus. Consistent with these observations, aspirin transiently increased p21, a protein involved in cell cycle arrest; however, the expression of the proapoptotic protein, Bax, was sustained. Treatment of cells with the anti-cancer drug, camptothecin, induced sustained induction of p21. Co-treatment with both camptothecin and aspirin decreased the expression of p21. Aspirin also potentiated camptothecin-induced cell death as measured by MTT assay, clonogenic cell survival assay and annexin V binding assay. Our results suggest that p53 pathway may contribute to the anti-cancer properties of aspirin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4038. doi:10.1158/1538-7445.AM2011-4038
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