Caffeic acid phenethyl ester modulates Helicobacter pylori-induced nuclear factor-kappa B and activator protein-1 expression in gastric epithelial cells

1 Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives (honeybee resin), has anti-inflammatory, anti-carcinogenic and anti-bacterial properties. This study was designed to investigate the anti-inflammatory effects of CAPE on Helicobacter pylori-induced NF-kappa B and AP-1 in the gastric epithelial cell line AGS. 2 Electrophoretic mobility shift assay was used to measure NF-kappa B- and AP-1-DNA binding activity. Western blotting was used to detect I kappa B-alpha and COX-2 expression in AGS cells cocultured with H. pylori. The antiproliferative effect of CAPE was measured by MTT assay. 3 Our results showed that caffeic phenethyl ester inhibits H. pylori-induced NF-kappa B and AP-1 DNAbinding activity in a dose (0.1 - 25 mu gml(-1) 0.35-88 mu M) and time- (15-240 min) dependent manner in AGS cells. Maximum inhibition by CAPE was observed at concentrations of 25 mu g ml(-1) (similar to 88 mu M) CAPE prevented H. pylori- and cytokine- induced degradation of I kappa B-a protein. 4 Pretreatment of AGS cells with CAPE also blocked cytokine- and mitogen-induced NF-kB and AP-1 expression. Furthermore, CAPE suppressed H. pylori- induced cell proliferation and production of the cytokines TNF-alpha and IL-8. In addition, CAPE blocked H. pylori- induced COX-2 expression. 5 The inhibition of such transcription by CAPE could result in suppression of many genes during H. pylori- induced inflammation, and also provide new insights into the anti-cancer and anti-inflammatory properties of CAPE.