An illustration of the experimental workflow as well as the data analysis for this study is shown in Fig. 8. The proteins from five experimental groups, including the control group (Ctr), Cos treated group, Dehy treated group, CD (Cos/Dehy = 1/2, w/w; simulating the composition ratio of VOSL) treated group, and VOSL treated group, were harvested and quantified. The quantified proteins were reduced and alkylated, and then digested into peptides. After TiO2-based enrichment, the phosphopeptides in each group were labeled by 4-plex iTRAQ reagent separately. The labeled phosphopeptides were mixed into two pools, thereinto, one pool was consisted of Cos-treated group (labeled with m/z 117 isotope ion) and Ctr group (labeled with m/z 114 isotope ion), and the other pool was consisted of Ctr group (labeled with m/z 114 isotope ion), Dehy-treated group (labeled with m/z 115 isotope ion), CD treated group (labeled with m/z 116 isotope ion), and VOSL treated group (labeled with m/z 117 isotope ion). The resulting phosphopeptide pools were desalted and then injected into liquid chromatography- tandem mass spectrometry (LC-MS/MS) system. The phosphopeptides in each group were relatively quantified by reporter ions and identified based on sequence information from MS/MS. Identified differential expression proteins were further analyzed using Ingenuity Pathways Analysis (IPA) (version 9.0) (Ingenuity® Systems, http://www.ingenuity.com) to statistically determine the functions and pathways most strongly associated with the protein list. Finally, the results of bioinformatics analysis were validated by cell cycle and apoptosis experiments, and Western blot experiments.