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

Asian Pac J Cancer Prev. 2021 Mar 1;22(3):909-918. doi: 10.31557/APJCP.2021.22.3.909.

Abstract

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.

Keywords: Atractylodes lancea (Thunb) D.C; LC-MS/MS; bile duct; cancer.

MeSH terms

  • Ammonia / metabolism
  • Apoptosis / drug effects*
  • Bile Duct Neoplasms / metabolism*
  • Blood Coagulation
  • Cell Line, Tumor
  • Cholangiocarcinoma / metabolism*
  • DNA Repair
  • Humans
  • MAP Kinase Signaling System
  • Metabolomics*
  • Methionine / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proteomics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Purines / metabolism
  • Sesquiterpenes, Eudesmane / pharmacology*
  • Signal Transduction
  • Urea / metabolism
  • Wound Healing

Substances

  • Purines
  • Sesquiterpenes, Eudesmane
  • beta-eudesmol
  • Ammonia
  • Urea
  • Methionine
  • Proto-Oncogene Proteins c-akt