It is well known that p21cip1 is a cyclin-dependent kinase inhibitor that directly inhibits the activity of cyclin E/CDK2 and cyclin D/CDK4/6 complexes, thus inhibiting Rb phosphorylation. p21cip1 functions as a CBR 5884 regulator of cell cycle progression at S phase. Highly expressed p21cip1 would inhibit cell proliferation. What is interesting is that even though the expression of p27kip1 gene and mRNA remained unchanged after LC treatment, p27kip1 protein level dose- and time-dependently increased with LC treatment. p27kip1 protein, like p21cip1, increased at a relatively low dose and at an early time point, which implied that p27 protein accumulation is possibly regulated at a post-translational level. Previous studies have reported that protein modification by phosphorylation or CPPHA acetylation would affect the stability of modified proteins. It is a general mechanism by which protein acetylation or sumoylation modulates ubiquitinationdependent proteasome proteolysis. For example, both acetylation and ubiquitination can modify the same lysine residues at the C terminus of p53, implicating a role of acetylation in the regulation of p53 stability. Since LC could induce the acetylation of multiple proteins, protein acetylation by interfering protein ubiquitination could be one of the mechanisms to affect p27 protein degradation, thus inducing p27 accumulation, which need to be confirmed in the future study. As shown, LC could dose-dependently decreased Rb phosphorylation, a downstream target of both p21 and p27 protein. Therefore, p27 protein accumulation together with p21cip1 high expression would contribute to LC-mediated cytotoxicity. However, we have also noticed that after LC treatment increased not only histone protein acetylation but also other protein acetylation as well, which suggests that other mechanisms are possibly involved in LC-mediated cytotoxicity in cancer cells. In recent years, protein acetylation has emerged as a major posttranslational modification for proteins. The regulatory scope of lysine acetylation is broad and comparable with that of other major posttranslational modifications including protein phosphorylation, sumoylation, ubiquitination and methylation. Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. 3600 lysine acetylation sites on 1750 proteins and quantified acetylation changes in response to the deacetylase inhibitors have been identified. It is found that lysine acetylation preferentially targets large macromolecular complexes involved in diverse cellular processes, such as chromatin remodeling, cell cycle, nuclear transport, splicing, and actin nucleation. Other study further confirmed that virtually every enzyme in glycolysis, gluconeogenesis, the tricarboxylic acid cycle, the urea cycle, fatty acid metabolism, and glycogen metabolism was found to be acetylated in human liver tissue, suggesting that lysine acetylation plays a major role in cell metabolisim and cell viability.