Carotenoids and retinoids stimulate gap junctional communication (GJC), tho
ught to be related to cancer-preventive properties. Lycopene, a nonprovitam
in A carotenoid and its possible oxidation product, acyclo-retinoic acid, w
ere tested for their effect on GJC, on stabilization of connexin43 mRNA, an
d on the transactivation of the RAR-beta 2-promoter in vitro. In human feta
l skin fibroblasts, GJC was stimulated by lycopene and acyclo-retinoic acid
. Lycopene was effective at a concentration of 0.1 mu M, whereas higher amo
unts of acyclo-retinoic acid (1 mu M) were needed for comparable stimulatio
n. Stabilizing effects of acyclo-retinoic acid on the mRNA of connexin43 vi
a elements located in the 3'-UTR were weak. In comparison to retinoic acid
(0.1 mu M), considerably higher concentrations of the acyclo analog (50 mu
M) were required for similar effects; lycopene (0.1 mu M) was not active in
this system. Likewise, unphysiologically high levels of acyclo-retinoic ac
id (50 mu M) were necessary to transactivate the RAR-beta 2 promoter. The d
ata demonstrate that acyclo-retinoic acid is much less active than retinoic
acid with respect to GJC and retinoid-related signaling, Therefore, we con
clude that lycopene affects GJC independent of the formation of acyclo-reti
noic acid. (C) 2000 Academic Press.