Cellular Physiology and Biochemistry (Aug 2017)

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

  • Hsing-Chun Kuo,
  • Yur-Ren Kuo,
  • Kam-Fai Lee,
  • Meng-Chiao Hsieh,
  • Cheng-Yi Huang,
  • Yung-Yu Hsieh,
  • Ko-Chao Lee,
  • Hsiang-Lan Kuo,
  • Li-Ya Lee,
  • Wan-Ping Chen,
  • Chin-Chu Chen,
  • Shui-Yi Tung

DOI
https://doi.org/10.1159/000480338
Journal volume & issue
Vol. 43, no. 1
pp. 195 – 208

Abstract

Read online

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