Sterol and Triterpene Derivatives from Plants Inhibit the Effects of a Tumor Promoter, and Sitosterol and Betulinic Acid Inhibit Tumor Formation in Mouse Skin Two-Stage Carcinogenesis

A single topical application of 1 jag of 12–O-tetradecanoylphorbol-13-acetate (TPA) to the ears of mice was shown to induce edema, and this TPA-induced inflammation was inhibited by 4-methylsterol and triterpene derivatives. The ED50 of these compounds against TPA-induced inflammation was 0.1–3 μmol. Phytosterols had only slight inhibitory effects. Furthermore, application of 5 μg TPA to mouse skin rapidly caused accumulation of ornithine decarboxylase (ODC). Similarly, sitosterol and lupane-type triterpene derivatives markedly inhibited this TPA-induced ODC accumulation. In addition, 5 umol betulinic acid markedly inhibited the promoting effect of 2.5 μg TPA applied twice weekly on skin tumor formation in mice initiated with 50 ug of 7,12-dimethylbenz[a]anthracene, and 5 μmol of sitosterol caused slight suppression. Thus, the inhibitory effects of sterol and triterpene derivatives on TPA-induced inflammation roughly parallelled their inhibitory activities against tumor promotion.