Inhibitory effect of ailanthoidol on 12-O-tetradecanoyl-phorbol-13-acetate-induced tumor promotion in mouse skin

Abstract

Many components derived from dietary or medicinal plants showing antioxidant and anti-inflammatory potential have been found to possess chemopreventive properties. In our previous study, we achieved the total synthesis of ailanthoidol (AT), a neolignan from Zanthoxylum ailanthoides or Salvia miltiorrhiza Bunge, which are used in Chinese traditional herbal medicine. In the present study, preliminarily, AT exhibited a radical quenching property by DPPH assay. Following this, we assessed the effect of AT on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress and inflammation in female CD-1 mouse skin which was closely linked to tumor promotion. The topical application of AT (0.5-2.5 mM; 200 microl) reduced the formation of hydrogen peroxide and inhibited the myeloperoxidase (MPO) activity in the mouse skin when compared with that of the TPA-treated alone group. In addition, AT presented a suppression effect on the TPA-induced hyperplasia and leukocyte infiltration in the epidermis and edema of mouse ears. Furthermore, it showed that AT inhibited the TPA-induced expression of COX-2 protein and ornithine decarboxylase (ODC) activity in epidermis. Finally, AT was evaluated for its ability to inhibit the TPA-induced promotion in skin tumors of female CD-1 mice. Topical application of AT 5 min prior to TPA (5 nmol) three times weekly for 12 weeks to mice which were initiated with benzo[a]pyrene (B[a]P) inhibited the incidence of skin tumors in mice and the average number of tumors per mice as compared to TPA-treated alone. These results indicate that AT possesses potential as a chemopreventive agent against tumor promotion.