title: EGFR tyrosine kinase inhibitory peptide attenuates Helicobacter pylori-mediated hyper-proliferation in AGS enteric epithelial cells.
abstract: Helicobacter pylori infection is one of the most critical causes of stomach cancer. The current study was conducted to explore the protective effects of an isolated active peptide H-P-6 (Pro-Gln-Pro-Lys-Val-Leu-Asp-Ser) from microbial hydrolysates of Chlamydomonas sp. against H. pylori-induced carcinogenesis. The peptide H-P-6 has effectively suppressed H. pylori-induced hyper-proliferation and migration of gastric epithelial cells (AGS). However, the peptide did not inhibit the viability of the bacteria or invasion into AGS cells. Therefore, the effect of the peptide on regulating H. pylori-induced molecular signaling was investigated. The results indicated that H. pylori activates the EGFR tyrosine kinase signaling and nuclear translocation of the β-catenin. The EGFR activation has led to the up-regulation of PI3K/Akt signaling pathway. Moreover, the nuclear translocation levels of β-catenin were significantly increased as a result of Akt mediated down-regulation of GSK3/β protein levels in the cytoplasm. Both of these consequences have resulted in increased expression of cell survival and migration related genes such as c-Myc, cyclin-D, MMP-2 and matrilysin. Interestingly, the isolated peptide potently inhibited H. pylori-mediated EGFR activation and thereby down-regulated the subsequent P13K/Akt signaling leading to β-catenin nuclear translocation. The effect of the peptide was confirmed with the use of EGFR tyrosine kinase inhibitor AG1487 and molecular docking studies. Collectively this study identifies a potent peptide which regulates the H. pylori-induced hyper-proliferation and migration of AGS cells at molecular level.
authors.affiliation: Marine Bio-Process Research Center, Pukyong National University, Nam-Gu, Busan, 608-737, Republic of Korea.
authors.forename: S W A
authors.initials: SW
authors.lastname: Himaya
authors.forename: Pradeep
authors.initials: P
authors.lastname: Dewapriya
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002696:Chlamydomonas / Q000378:metabolism; D004848:Epithelium; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000382:microbiology* / Q000648:ultrastructure; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009842:Oligopeptides / Q000302:isolation & purification / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000209:etiology
chemical_list: C582240:H-P-6 peptide; D009842:Oligopeptides; D066246:ErbB Receptors