Abstract 2942: Acetylation of intracellular protein induces apoptotic cell death in Aspirin-treated human breast cancer cells.

Abstract

Abstract Acetylation is one of the dynamic post-translational modification of lysine residues on protein determining the structure, function and intracellular localization that plays an important role in the signal transduction pathways related to diverse cell functions - proliferation, cell death, and differentiation as well as transcriptional regulation. Recently, it has been reported that acetylating agents including chemical histone deacetylase inhibitors and plant polyphenols lead to the increased acetylation of histone and non-histone proteins, which induces to rapid cancer cell death. In this present study, we are focused on molecular mechanism of cell death in two Aspirin-treated human breast cancer cells, MCF-7 and MDA-MB-231. Trichostatin A (TSA) treatment was combined for maintaining acetylation of intracellular proteins at 0.1 μM concentration, which was not caused cell death itself. It was observed that Aspirin/TSA treatment caused the significant inhibition of cell growth in a dose- and time-dependent manner in both MDA-MB-231 and MCF-7 cells. The induced cell death in MDA-MB-231 by Aspirin/TSA treatment was associated with several specific features of apoptosis, which were proved by biochemical assays containing DNA fragmentation, Annexin V staining and cell cycle analysis. On the other hand, the exposure of MCF-7 to Aspirin/TSA caused necrotic rather than apoptotic mechanism judged by DNA fragmentation assay. These results suggest that different cell death pathway in two breast cancer cell lines is implicated in acetylated protein mediated signals. Previous reports suggest sporadic tumor cell necrosis is associated with extracellular release of cellular protein such as the high mobility group box 1 and may activate innate immune system. Interestingly, we confirmed secretory protein in cell-culture supernatant by immunoprecipitation using anti-acetyllysin antibody. Secretion of the acetylated protein was elevated dose- and time- dependent manner after Asprin treatment. Although extracellular role of the secretory protein in response to acetylation has not been clearly identified yet, this acetylated protein may be involved in initiation of apoptotic cell death signals and/or activating innate immune response. Taken together, theses results indicated that acetylated protein plays an essential role in anti-tumorigenesis in response to acetylating agent such as Aspirin. Citation Format: Yu Ran Lee, Byeong Hwa Jeon, Sunga Choi. Acetylation of intracellular protein induces apoptotic cell death in Aspirin-treated human breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2942. doi:10.1158/1538-7445.AM2013-2942 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.