Carotenoids Upregulate Cell-to-Cell Communication and Connexin43 Gene Expression in Human Dermal Fibroblast Cells
Carotenoids are plant pigments found in vegetables and fruits as common components of the human diet. Evidence from epidemiological and experimental studies has shown that carotenoids have anticancer action. However, their mode of action is unknown. We have previously reported that carotenoids, which inhibit carcinogen-induced neoplastic transformation of mouse fibroblast cells, increase gap junctional communication (GJC) [Carcinogenesis, 12:2109 (1991)], induce the gene expression of connexin43 (Cx43), a gene coding for a major gap junctional protein in various cells and tissues, and this activity is highly correlated with their ability to inhibit transformation. Here, we extend these carotenoid effects on murine cells to human dermal fibroblasts. Using a dye microinjection method, we found that carotenoids, β-carotene and canthaxanthin, strongly enhance GJC in a dose- and time-dependent manner. Northern and Western blotting revealed that this enhanced communication was accompanied by an increase in the levels of Cx43 mRNA and protein. Immunofluorescence microscopy using a connexin43 antibody demonstrated that carotenoids induced many junctional plaques in regions of cell-to-cell contact. Since GJC plays an important role in cell growth control, we propose that much of the chemopreventive action of carotenoids in humans could be explained by the enhanced intercellular transfer of growth regulatory signals. Since canthaxanthin, a nonprovitamin A carotenoid, is as active as the provitamin A carotenoid, β-carotene, the induction of GJC and Cx43 gene expression by carotenoids is unlikely to be due to provitamin A properties.