COMPARISON OF THE INHIBITORY EFFECTS OF MONOMERIC, DIMERIC, AND TRIMERIC PROCYANIDINS ON THE BIOCHEMICAL MARKERS OF SKIN TUMOR PROMOTION IN MOUSE EPIDERMIS IN-VIVO

Several procyanidin dimers and an epicatechin trimer purified from Douglas hr bark tannins were compared with their monomer components (+)-catechin and (-)-epicatechin for their abilities to inhibit the biochemical effects of the potent tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) in mouse epidermis in vivo. Topical applications of the procyanidins, 15 min before the tumor promoter, inhibit TPA-induced ornithine decarboxylase (ODC) activity and this inhibition increases with the degree of polymerization (trimer > dimer > monomer). At a dose of 10 mu mol, all procyanidin dimers inhibit the ODC response to TPA to a greater degree than 20 mu mol of epicatechin and 10 mu mol of epicatechin and/or catechin. Under similar conditions, catechin and epicatechin fail to inhibit the hydroperoxide (HPx) response to TPA whereas the procyanidin dimers inhibit this response by almost 40 %. At a dose of 10 mu mol, the epicatechin trimer also inhibits TPA-induced ODC activity and HPx production to a greater degree than 10-30 mu mol of epicatechin. However, these various treatments with monomeric, dimeric, and trimeric procyanidins do not differ significantly in their abilities to inhibit TPA-stimulated DNA synthesis. These results suggest that some of the antitumor-promoting effects of procyanidins might increase at the biflavanoid and triflavanoid levels.