APIGENIN AND TANGERETIN ENHANCE GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN RAT-LIVER EPITHELIAL-CELLS

Two flavones, apigenin and tangeretin, were studied for their ability to modulate gap junctional intercellular communication (GJIC) in the r at liver epithelial cell line REL. Their cytotoxicity was first determ ined by cell density and neutral red uptake assays: neither apigenin n or tangeretin are cytotoxic at 10 and 25 mu M, the concentrations used in our experiments. We then studied GJIC using the dye transfer assay and we observed that both apigenin and tangeretin enhance it, the max imum stimulation (x 1.7-1.8) being achieved at 25 mu M for 24 h. When the dye transfer was enhanced, the amount of connexin 43 increased, wh ich was demonstrated by Western blot and immunofluorescence analysis. For apigenin only, Northern blot analysis showed an accumulation of co nnexin 43 mRNA. In addition, the incubation of REL cells with the two compounds, for 1 or 24 h, prevented the inhibition of dye transfer by 12-O-tetradecanoylphorbol-13-acetate (1 or 10 ng/ml). The enhancement of GJIC by apigenin could be one of the major mechanisms responsible f or apigenin's anti-tumour promoting action in vivo. As for tangeretin, its capacity to enhance GJIC completes its potential protective prope rties towards the post-initiation process.