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

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.

Effect of ingestion of cow's milk protein hydrolysate formulas on alpha-casein-specific immunoglobulin E and G1 antibody responses in naïve and sensitized mice.

OBJECTIVES: Cow's milk protein hydrolysate formulas are widely used for genetically predisposed atopic infants. Whether hydrolysate formulas can induce oral tolerance to alpha-casein was studied for the first time in naive and sensitized mice. METHODS: Using immunoblotting, residual antigenicity to alpha-casein was examined for in animals fed hydrolysate formulas. Naïve mice fed hydrolysate formulas for 1 to 4 weeks were later sensitized with alpha-casein. Another group of mice sensitized first with alpha-casein were then fed hydrolysate formulas continually for 12 weeks. RESULTS: Oral tolerance measured by immunoglobulin (Ig)E and IgG1 antibody responses to alpha-casein was induced in naïve mice fed NAN for 1 week or NAN-HA for 4 weeks. IgE responses to alpha-casein were suppressed in mice fed NAN-HA for 1 week or Neoangelac FL for 4 weeks. In contrast, mice fed Alfare, Pepti-Junior, or Pregestimil for 1 to 4 weeks did not develop tolerance to alpha-casein. Antibody responses to alpha-casein were not significantly suppressed in sensitized mice fed NAN or hydrolysate formulas for 12 weeks. CONCLUSIONS: Primary IgE responses to alpha-casein are readily suppressed in naïve mice first fed cow's milk formula or partially hydrolyzed formula for 1 week. Conversely, ongoing IgE, IgG1, and IgG antibody responses to alpha-casein are poorly suppressed in previously sensitized mice even after prolonged feeding of cow's milk formula or hydrolysate formulas.