Abstract
FK228 is a selective inhibitor of histone deacetylases that exhibits marked antitumor activity in cancer cells and xenograft models. However, the effect of FK228 on the global profile of histone lysine acetylation and the proteome of EC109 cells remains poorly understood. The present study aimed at analyzing histone lysine acetylation and identifying the proteomic changes in EC109 cells following treatment with FK228, using the stable isotope labelling by amino acids in cell culture technique and a high-sensitivity mass spectrometer. In total, 87 acetylation sites and 3,515 proteins revealed changes in response to FK228 treatment. Of the 87 acetylation sites, 25 were quantifiable and 19 were quantified with ratio of >1.3. Notably, no downregulated lysine acetylation (Kac) sites were quantified in the present study and the 62 unquantified Kac sites were only identified in the FK228-treated cells. Bioinformatic analysis revealed that these quantifiable proteins were primarily involved in multiple biological functions and metabolic pathways as well as in protein complexes. The results of the present study revealed the extensive lysine acetylome and proteome in EC109 cells and expanded upon the current understanding of the anticancer mechanism of FK228 in EC109 cells.