Inhibitory effect of ailanthoidol on 12-O-tetradecanoyl-phorbol-13-acetate-induced tumor promotion in mouse skin.
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.
Lee
Yean-Jang
YJ
Department of Chemistry, National Changhua University of Education, Changhua, Taiwan, ROC.
Kao
Erl-Shyh
ES
Chu
Chia-Yih
CY
Lin
Wea-Lung
WL
Chiou
Yea-Huey
YH
Tseng
Tsui-Hwa
TH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology*; D002273:Carcinogens; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009369:Neoplasms / Q000188:drug therapy*; D009195:Peroxidase / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D001572:Benzofurans; D002273:Carcinogens; C476933:ailanthoidol; D001564:Benzo(a)pyrene; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate