β-Carotene Inhibits Expression of Matrix Metalloproteinase-10 and Invasion in -Infected Gastric Epithelial Cells.

Matrix metalloproteinases (MMPs), key molecules of cancer invasion and metastasis, degrade the extracellular matrix and cell-cell adhesion molecules. MMP-10 plays a crucial role in -induced cell-invasion. The mitogen-activated protein kinase (MAPK) signaling pathway, which activates activator protein-1 (AP-1), is known to mediate MMP expression. Infection with , a Gram-negative bacterium, is associated with gastric cancer development. A toxic factor induced by infection is reactive oxygen species (ROS), which activate MAPK signaling in gastric epithelial cells. Peroxisome proliferator-activated receptor γ (PPAR-γ) mediates the expression of antioxidant enzymes including catalase. β-Carotene, a red-orange pigment, exerts antioxidant and anti-inflammatory properties. We aimed to investigate whether β-carotene inhibits -induced MMP expression and cell invasion in gastric epithelial AGS (gastric adenocarcinoma) cells. We found that induced MMP-10 expression and increased cell invasion via the activation of MAPKs and AP-1 in gastric epithelial cells. Specific inhibitors of MAPKs suppressed -induced MMP-10 expression, suggesting that induces MMP-10 expression through MAPKs. β-Carotene inhibited the -induced activation of MAPKs and AP-1, expression of MMP-10, and cell invasion. Additionally, it promoted the expression of PPAR-γ and catalase, which reduced ROS levels in -infected cells. In conclusion, β-carotene exerts an inhibitory effect on MAPK-mediated MMP-10 expression and cell invasion by increasing PPAR-γ-mediated catalase expression and reducing ROS levels in -infected gastric epithelial cells.