Restoration of gap junctional intercellular communication by caffeic acid phenethyl ester (CAPE) in a ras-transformed rat liver epithelial cell line

Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having anti-inflammatory, anti-viral and anti-cancer properties. Since the deficiency of gap junctional intercellular communication (GJIC) has been shown to be a characteristic of most cancer cells, this study was designed to test the hypothesis that the anti-carcinogenic activity of CAPE might be related to its ability to restore GJIC in tumorigenic GJIC-deficient cells (WB-ras2 cells). The results showed that CAPE restored GJIC, phosphorylation of connexin 43 (Cx43) and its normal localization on the plasma membrane in WB-ras2 cells after 3 days at 5 μg/ml concentration. Additionally, CAPE inhibited growth in soft agar and decreased the protein level of p21ras. The results are consistent with the hypothesis that the anti-cancer mechanism of CAPE may be mediated by its ability to restore GJIC.