INHIBITORY EFFECTS OF SEMISYNTHETIC FLAVONOID DERIVATIVES ON THE BIOCHEMICAL MARKERS OF TUMOR PROMOTION IN MOUSE EPIDERMIS IN-VIVO

Two sets of flavonoid derivatives were synthesized from condensed tannins (CTs) or catechin, and compared with the procyanidin monomer models, (+)-catechin and (-)-epicatechin, for their abilities to inhibit the biochemical effects of the potent tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in mouse epidermis in vivo. Topical applications of the semisynthetic flavonoids, catechin dialkyl ketals and epicatechin-4-alkylsulphides inhibit TPA-induced ornithine decarboxylase (ODC) activity to a much greater degree than catechin or epicatechin. Moreover, they reduce TPA-stimulated hydroperoxide (HPx) production, a response that cannot be inhibited by catechin or epicatechin. These compounds also inhibit the sequential stimulations of protein and DNA synthesis linked to TPA promotion. The remarkable effectiveness of these synthetic compounds, especially against the ODC marker of skin tumor promotion, suggests that they may be effective anti-tumor promoters.