Biological Activities of Apo-canthaxanthinoic Acids Related to Gap Junctional Communication

Apo-carotenoids with different numbers of conjugated double bonds are formed upon excentric cleavage of carotenoids. These compounds may exhibit biological activities similar to those of the parent carotenoids or their central cleavage products, the retinoids. 11-Apo-canthaxanthin-11-oic acid, 13-apo-canthaxanthin-13-oic acid, and 14′-apo-canthaxanthin-14′-oic acid, carrying 2, 3, or 5 conjugated double bonds in the polyene chain, respectively, were tested for their effects on gap junctional communication (GJC), on stabilization of connexin43 mRNA, and on the activation of the retinoic acid-β2 receptor (RAR-β2 receptor); the effects were compared to those of retinoic acid and 4-oxo-retinoic acid, known to stimulate GJC and to activate the RAR-β2 receptor. The effects of 4-oxo-retinoic acid were comparable to those of retinoic acid. 4-Oxo-retinoic acid, like retinoic acid, influences the stability of connexin 43 mRNA via elements located in the 3′-UTR. No effects were observed with the short-chain apo-canthaxanthinoic acids. A small but statistically significant induction of GJC and transactivation activity towards the RARβ2 was found with 14′-apo-canthaxanthin-14′-oic acid. This might be due to biological effects of the compound itself or to biologically active breakdown products. The data suggest that the major biological effects of canthaxanthin on retinoid signaling pathways are related to activities mediated by the products of the central cleavage.