A Comparative Proteomic Analysis of Erinacine A's Inhibition of Gastric Cancer Cell Viability and Invasiveness

Cell Physiol Biochem. 2017;43(1):195-208. doi: 10.1159/000480338. Epub 2017 Aug 30.


Background / Aims: Erinacine A, isolated from the ethanol extract of the Hericium erinaceus mycelium, has been demonstrated as a new alternative anticancer medicine. Drawing upon current research, this study presents an investigation of the molecular mechanism of erinacine A inhibition associated with gastric cancer cell growth.

Methods: Cell viability was determined by Annexin V-FITC/propidium iodide staining and migration using a Boyden chamber assay to determine the effects of erinacine A treatment on the proliferation capacity and invasiveness of gastric cancer cells. A proteomic assay provided information that was used to identify the differentially-expressed proteins following erinacine A treatment, as well as the mechanism of its targets in the apoptotic induction of erinacine A.

Results: Our results demonstrate that erinacine A treatment of TSGH 9201 cells increased cytotoxicity and the generation of reactive oxygen species (ROS), as well as decreased the invasiveness. Treatment of TSGH 9201 cells with erinacine A resulted in the activation of caspases and the expression of TRAIL. Erinacine A induction of apoptosis was accompanied by sustained phosphorylation of FAK/AKT/p70S6K and the PAK1 pathways, as well as the generation of ROS. Furthermore, the induction of apoptosis and anti-invasion properties by erinacine A could involve the differential expression of the 14-3-3 sigma protein (1433S) and microtubule-associated tumor suppressor candidate 2 (MTUS2), with the activation of the FAK/AKT/p70S6K and PAK1 signaling pathways.

Conclusions: These results lead us to speculate that erinacine A may generate an apoptotic cascade in TSGH 9201 cells by activating the FAK/AKT/p70S6K/PAK1 pathway and upregulating proteins 1433S and MTUS2, providing a new mechanism underlying the anti-cancer effects of erinacine A in human gastric cancer cells.

Keywords: 1433S; Erinacine A; FAK; MTUS2; ROS; p70S6K.

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Humans
  • Phosphorylation / drug effects
  • Proteome / analysis
  • Proteomics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • TNF-Related Apoptosis-Inducing Ligand / metabolism


  • 14-3-3 Proteins
  • Antineoplastic Agents
  • Diterpenes
  • Proteome
  • Reactive Oxygen Species
  • TNF-Related Apoptosis-Inducing Ligand
  • erinacine A
  • Focal Adhesion Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Caspases