Comparison of the Inhibitory Effects of Monomeric, Dimeric, and Trimeric Procyanidins on the Biochemical Markers of Skin Tumor Promotion in Mouse Epidermis in vivo

Abstract

Several procyanidin dimers and an epicatechin trimer purified from Douglas fir 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 µmol, all procyanidin dimers inhibit the ODC response to TPA to a greater degree than 20 µmol of epicatechin and 10 µmol 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 µmol, the epicatechin trimer also inhibits TPA-induced ODC activity and HPx production to a greater degree than 10 - 30 µmol 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.

Key words

Procyanidins - Pseudotsuga - Pinaceae - ornithine decarboxylase - hydroperoxides - DNA synthesis - tumor promotion - mouse skin