Studies of the Chemopreventive Actions of Carotenoids and Retinoids

Abstract

Multiple epidemiological studies have shown that the consumption of dietary carotenoids is linked to a decreased risk of cancer. Experiments in murine cells have supported the fact that carotenoids, regardless of their provitamin A activity, can function as chemopreventive agents. Their ability to inhibit neoplastic transformation appears to be analogous to that of a related class of compounds known as the retinoids (vitamin A derivatives). In mouse C3H IOTI/2 cells, chemopreventive activity is correlated with the ability of these two compounds to upregulate intercellular communication through gap junctions. Gap junctions, comprised of a family of proteins known as the connexins, serve as conduits for small molecules and ions proposed to be involved in cell growth regulation. Previous experiments have shown that there is an increase in Cx43 mRNA, preceding an increase in Cx43 protein, when gap junctional communication (GJC) is upregulated by retinoids and carotenoids. This increase in Cx43 mRNA could be the result of increased transcription, or increased mRNA stability. Here, we present the results from experiments designed to examine the stability of Cx 43 mRNA. Our data indicates that upon treatment of C3H 1OT112 cells with 2x1o-6 M of canthaxanthin, a carotenoid, or 2x10-8 M of tetrahydrotetramethylnaphalenylpropenyl benzoic acid (TTNPB), a synthetic retinoid, the half-life of Cx 43 mRNA is not prolonged in comparison with cells that were not treated with either compound. This suggests that the increase in the expression of Cx 43 mRNA in the cell, after treatment with a carotenoid or retinoid, may be the result of increased transcription rather than increased mRNA stability. In addition, we have also found through the use of cycloheximide, that carotenoids and retinoids upregulate Cx43 mRNA directly, independent of the de novo synthesis of proteins in the cell.