The Proteomics and Metabolomics Analysis for Screening the Molecular Targets of Action of β-Eudesmol in Cholangiocarcinoma

OBJECTIVE: β-eudesmol is the active compound isolated from Atractylodes lancea (Thunb) D.C. The actions of this compound against cholangiocarcinoma (CCA) cells include anti-angiogenesis and anti-cell proliferation and growth. For more understanding of the molecular targets of action of β-eudesmol, the CCA cells (CL-6) were exposed to β-eudesmol for 24 and 48 hours. METHODS: Proteins and metabolites from the intra- and extra-cellular components of the CL-6 cells were extracted and identified by LC-MS/MS. Protein analysis was performed using the Venn diagram (protein grouping), PANTHER (gene ontology), and STITCH software (protein-protein interaction). Metabolite analysis including their interactions with proteins, was performed using MetaboAnalyst software. RESULTS: The analysis showed that the actions of β-eudesmol were associated with various biological processes particularly apoptosis and cell cycle. These included blood coagulation, wound healing, DNA repair, PI3K-Akt signaling pathway, immune system process, MAPK cascade, urea cycle, purine metabolism, ammonia recycling, and methionine metabolism. CONCLUSION: Possible molecular targets of action of β-eudesmol against CL-6 for cell apoptosis induction were TNFRSf6, cytochrome C, BAX3, DHCR24, CD29, and ATP. On the other hand, possible targets for cell cycle arrest induction were CDKN2B, MLF1, TFDP2, CDK11-p110, and nicotinamide.