Vitamin A acid (retinoic acid), a potent inhibitor of 12-O-tetradecanoyl-phorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis

A K Verma, R K Boutwell
1977 Cancer Research  
Topical application of retinole acid to mouse skin led to a dramatic inhibition of phorbol ester (12-O-tetradecanoylphorbol-13-acetate)-induced epidermal ornithine decarboxylase (EC activity, an event proposed to be essen tial for tumor promotion. The degree of inhibition was de pendent on the dose and time of application of retinoic acid. In contrast, treatment with retinoic acid did not de press significantly the phorbol ester-induced S-adenosylmethionine decarboxylase (EC
more » ... activity, a second enzyme in the pathway of polyamine biosynthesis. A number of natural vitamin A analogs (retinoids) were tested for their ability to inhibit tetradecanoyl-phorbol-acetate-induced epidermal ornithine decarboxylase activity and were found to be potent in the following order: retinoic acid > retinal > retinol > retinyl acetate > retinyl palmitate. The ability of retinoids to inhibit tetradecanoyl-phorbol-acetateinduced epidermal ornithine decarboxylase activity corre lated with their ability to inhibit skin tumor promotion. Mixing of soluble extracts from tetradecanoyl-phorbolacetate-treated mouse epidermis pretreated with either reti noic acid or acetone gave essentially additive ornithine decarboxylase activity, arguing against the production of an inhibitor of tetradecanoyl-phorbol-acetate-induced orni thine decarboxylase activity. Furthermore, retinoic acid did not alter tetradecanoyl-phorbol-acetate-induced ornithine decarboxylase activity when added to the assay mixture under normal assay conditions.
pmid:861945 fatcat:opyn57yahrfh5k5n5scws3qia4