Some lupane-type triterpenes inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin

We have found that several lupane-type Triterpenes, including lupeol, its acetate, betulin and betulinic acid, inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, and that betulinic acid inhibits tumor promotion in two-stage carcinogenesis in mice. Among seven lupane-type Triterpenes assayed, these compounds inhibited the inflammatory activity induced by TPA in mice. The 50 % inhibitory dose of these compounds for TPA-induced inflammation was 0.4-4.0 μmol. Furthermore, topical application of lupeol, lupeol 3-acetate and betulin markedly suppressed the tumor-promoting effect of TPA (1 μg/mouse) in mouse skin initiated with 7,12-dimethyl-benz[a]anthracene (50 μg/mouse), at a grade corresponding to that of betulinic acid.