Document Detail


DA6034 promotes gastric epithelial cell migration and wound-healing through the mTOR pathway.
MedLine Citation:
PMID:  21793913     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND AIM: 7-Carboxymethyloxy-3',4',5-trimethoxy flavone (DA6034), a synthetic derivative of eupatilin, has a protective effect on gastric mucosa against various ulcerogens, and is currently in the phase III clinical trial in the treatment of peptic ulcer disease. Cell migration and/or growth plays a role in the repair process of gastric ulcer, so this study investigated the effect of DA6034 on the movement and proliferation of gastric epithelial cells and its associated signaling pathway.
METHODS: The migration of AGS or SNU484 human gastric epithelial cells was shown by scratch-induced wound healing and transwell assays, and the proliferation of the cells was assessed by FACS and proliferation assays.
RESULTS: Treatment of DA6034 promoted the migration of gastric epithelial cells in a concentration-dependent manner. DA6034 treatment facilitated the phosphorylation of mTOR that led to an increase in the activity of S6K1, indicating its ability to activate mTOR and S6K1. Rapamycin aborted the wound-healing effect of DA6034, which supported the role of mTOR activation in the wound-healing process. In addition, DA6034 treatment increased PI3K-dependent Akt phosphorylation, which was necessary for the enhancement of cell migration. DA6034, however, did not stimulate the proliferation of gastric epithelial cells, being consistent with no activation of ERK1/2 by the agent.
CONCLUSIONS: DA6034 has the ability to heal scratch wounds, which may result from an increase in gastric epithelial cell migration as mediated by PI3K-Akt-dependent activation of mTOR and S6K1. Our finding may be of help in understanding the molecular basis of the anti-ulcer effect of DA6034.
Authors:
Young Woo Kim; Woo Hyung Lee; Seul Min Choi; Yoon Young Seo; Byoung Ok Ahn; Soon Hoe Kim; Sang Geon Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of gastroenterology and hepatology     Volume:  27     ISSN:  1440-1746     ISO Abbreviation:  J. Gastroenterol. Hepatol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-20     Completed Date:  2012-05-15     Revised Date:  2012-10-17    
Medline Journal Info:
Nlm Unique ID:  8607909     Medline TA:  J Gastroenterol Hepatol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  397-405     Citation Subset:  IM    
Copyright Information:
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Affiliation:
Innovative Drug Research Center for Metabolic and Inflammatory Diseases, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Anti-Ulcer Agents / pharmacology*
Cell Line
Cell Movement / drug effects*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Enzyme Activation
Epithelial Cells / drug effects*,  enzymology,  pathology
Extracellular Signal-Regulated MAP Kinases / metabolism
Flavonoids / pharmacology*
Gastric Mucosa / drug effects*,  enzymology,  pathology
Humans
Phosphatidylinositol 3-Kinase / metabolism
Phosphorylation
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-akt / metabolism
Ribosomal Protein S6 Kinases, 70-kDa / metabolism
Signal Transduction / drug effects*
TOR Serine-Threonine Kinases / antagonists & inhibitors,  metabolism*
Time Factors
Wound Healing / drug effects*
Chemical
Reg. No./Substance:
0/7-carboxymethoxyloxy-3',4',5-trimethoxyflavone; 0/Anti-Ulcer Agents; 0/Flavonoids; 0/Protein Kinase Inhibitors; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.137/Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa; EC 2.7.11.1/ribosomal protein S6 kinase, 70kD, polypeptide 1; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
Comments/Corrections
Comment In:
J Gastroenterol Hepatol. 2012 Sep;27(9):1414-6   [PMID:  22908869 ]

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