Search

Background: Helicobacter pylori infection is a major risk factor in the development of gastric cancer. H. pylori infection of gastric epithelial cells increases the levels of reactive oxygen species (ROS), activates oncogenes, and leads to β-catenin-mediated hyper-proliferation. β-Carotene reduces ROS levels, inhibits oxidant-mediated activation of inflammatory signaling and exhibits anticancer properties. The present study was carried out to determine if β-carotene inhibits H. pylori -induced cell proliferation and the expression of oncogenes c-myc and cyclin E by reducing the levels of β-catenin and phosphorylated glycogen synthase kinase 3β (p-GSK3β)., Methods: Gastric epithelial AGS cells were pre-treated with β-carotene (5 and 10 μM) for 2 hours prior to H. pylori infection and cultured for 6 hours (for determination of the levels of p-GSK3β, GSK3β, and β-catenin) and 24 hours (for determination of cell viability and protein levels of c-myc and cyclin E). Cell viability was determined by the MTT assay and protein levels were determined via western blot-based analysis., Results: β-Carotene inhibited H. pylori -induced increases in the percentage of viable cells, phosphorylated GSK3β (p-GSK3β), and the levels of β-catenin, c-myc and cyclin E., Conclusions: β-Carotene inhibits H. pylori -induced hyper-proliferation of gastric epithelial cells by suppressing β-catenin signaling and oncogene expression., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed., (Copyright © 2019 Korean Society of Cancer Prevention.)

Gastric cancer, as well as inflammation, caused by Helicobacter pylori, activates the production of chemokines by activation of redox-sensitive transcription factor NF- κ B in gastric epithelial cells. Mitogen-activated protein kinases including extracellular signal-regulated kinase (ERK) and p38 kinase (p38) are activated by Helicobacter pylori, which may regulate NF- κ B activation in the infected cells. However the mechanisms how ERK and p38 induce NF- κ B activation have not been investigated. Present study aims to investigate the role of ERK and p38 on the activation of NF- κ B in Helicobacter pylori-infected AGS cells. Western blot analysis was performed for determining the levels of I κ B, p105, p50 and p65 in gastric epithelial cells infected with Helicobacter pylori and treated with ERK inhibitor U0126 and p38 inhibitor SB203580. Helicobacter pylori induced the degradation of I κ Bα and upregulation of p105, p50 and p65 in the infected cells. U0126 inhibited the degradation of I κ Bα while SB203580 suppressed expression of p105, p50 and p65 in Helicobacter pylori-infected cells. ERK and p38 differentially activate NF- κ B; ERK induces degradation of I κ Bα while p38 upregulates the expression of p50 and p65, subunits of NF-κB in Helicobacter pylori-infected gastric epithelial AGS cells.