Indomethacin Interferes with EGF-Induced Activation of Ornithine Decarboxylase in Gastric Cancer Cells

Abstract

Background/Aims: Epidermal growth factor (EGF) has a wide variety of biological activities in the protection of gastric mucosa against acute injury and the healing of gastric ulcer. However, the molecular basis of the EGF action remains unknown. EGF-induced activation of ornithine decarboxylase (ODC) was examined, because ODC is a key enzyme for the cell proliferation. Methods: The effects of epidermal growth factor (EGF) and indomethacin on ornithine decarboxylase (ODC) mRNA and enzyme activity were examined in gastric cancer derived KATO-III cells. Results: EGF induced both ODC mRNA expression and enzyme activation in a biphasic manner with the peaks at 0.5 and 3 h for mRNA and at 5 and 9 h for enzyme activity, respectively. Indomethacin pretreatment significantly reduced EGF-induced ODC activation and was completely abolished for the first 5 h. Conclusion: Since it has been reported that both EGF and ODC are involved in cell migration and proliferation, two actions of EGF for gastric mucosal healing may be through, at least in part, this biphasic activation of ODC. Indomethacin suppresses and changes the response of ODC induced by EGF.

High molecular protein of Helicobacter pylori responsible for inhibition of ornithine decarboxylase activity of human gastric cultured cells

“…As the H. pylori extract used in the present study did not affect the viability of gastric cells, the inhibitory effect of H. pylori extract on ODC activity was not due to cellular damage. ODC is regulated by growth factors such as epidermal growth factor (EGF), and EGF can stimulate ODC mRNA expression and enzyme activity of human gastric cultured cells 26 . H. pylori , especially VacA, interferes with binding of EGF to its receptor 10 and EGF‐activated signal transduction of gastric cells 27 .…”

Gastric mucosal cell protection by epidermal growth factor in primary monolayer culture of guinea pig gastric mucous cells

“…In the gastrointestinal tract, EGF enhances epithelial cell proliferation, inhibits gastric acid secretion, and exerts anti-ulcer and cytoprotective effects. [1][2][3][4][5][6][7][8][9][10][11][12][13] However, the mechanism by which EGF prevents gastric mucosal injury remains unclear. The cytoprotective effect of EGF has been suggested to be mediated through the enhancement of PG synthesis, as it has been shown that gastric mucosal PG and somatostatin, 5,6 as well as gastric mucin, are decreased in rats after submandibular gland resection.…”

“…One potential contributor to gastric mucosal defense is epidermal growth factor (EGF), which has various activities in the gastrointestinal tract, including enhancement of epithelial cell proliferation, inhibition of gastric acid secretion, an anti-ulcer effect, and a cytoprotective effect. [1][2][3][4][5][6][7][8][9][10][11][12][13] Additionally, we have suggested the importance of mucin as a mucosal protectant. 14,15 In the present study, we used a primary gastric mucous cell monolayer culture system [15][16][17] to investigate the gastric mucosal protective mechanisms of EGF at the cellular level.…”

Suppression of Growth Arrest and DNA Damage-Inducible 45α Expression Confers Resistance to Sulindac and Indomethacin-Induced Gastric Mucosal Injury

“…Mounting evidence indicates that NSAIDs also exert COX/ prostaglandin-independent effects, such as inhibition of epidermal growth factor signaling, regulation of cell cycle proteins such as p21 and cyclins, inhibition of the mitogenactivated protein-kinase pathway (Ishikawa et al, 1998;Tegeder et al, 2001), and increased ubiquitination of proteins such as hypoxia-inducible factor-1␣ and ␤-catenin in T cells for degradation by the ubiquitin-proteasome (Jones et al, 2002;Dihlmann et al, 2003). NSAIDs also directly activate proapoptotic factors such as caspases and Bax (Zhou et al, 2001), and they down-regulate levels of survivin, an antiapoptosis protein, both in vivo in human and rat gastric mucosa and in vitro in rat gastric epithelial RGM-1 cells (Chiou et al, 2005).…”