Stimulation of Gap Junctional Communication: Comparison of acyclo-Retinoic Acid and Lycopene

Carotenoids and retinoids stimulate gap junctional communication (GJC), thought to be related to cancer-preventive properties. Lycopene, a nonprovitamin A carotenoid and its possible oxidation product, acyclo-retinoic acid, were tested for their effect on GJC, on stabilization of connexin43 mRNA, and on the transactivation of the RAR-β2-promoter in vitro. In human fetal skin fibroblasts, GJC was stimulated by lycopene and acyclo-retinoic acid. Lycopene was effective at a concentration of 0.1 μM, whereas higher amounts of acyclo-retinoic acid (1 μM) were needed for comparable stimulation. Stabilizing effects of acyclo-retinoic acid on the mRNA of connexin43 via elements located in the 3′-UTR were weak. In comparison to retinoic acid (0.1 μM), considerably higher concentrations of the acyclo analog (50 μM) were required for similar effects; lycopene (0.1 μM) was not active in this system. Likewise, unphysiologically high levels of acyclo-retinoic acid (50 μM) were necessary to transactivate the RAR-β2 promoter. The data demonstrate that acyclo-retinoic acid is much less active than retinoic acid with respect to GJC and retinoid-related signaling. Therefore, we conclude that lycopene affects GJC independent of the formation of acyclo-retinoic acid.