Document Type: Research Articles
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Paholyothin Road, Klonglung, Pathumthani Thailand.
Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Paholyothin Road, Klonglung, Pathumthani Thailand.
Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathumthani, Thailand.
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.