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 microgram 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 mumol. Phytosterols had only slight inhibitory effects. Furthermore, application of 5 micrograms 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 mumol betulinic acid markedly inhibited the promoting effect of 2.5 micrograms TPA applied twice weekly on skin tumor formation in mice initiated with 50 micrograms of 7,12-dimethylbenz[a]anthracene, and 5 mumol 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.
Yasukawa
K
K
College of Pharmacy, Nihon University, Chiba, Japan.
Takido
M
M
Matsumoto
T
T
Takeuchi
M
M
Nakagawa
S
S
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009955:Ornithine Decarboxylase / Q000032:analysis; D053978:Pentacyclic Triterpenes; D010840:Phytosterols / Q000494:pharmacology*; D012855:Sitosterols / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid
D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D010840:Phytosterols; D012855:Sitosterols; D014315:Triterpenes; D015127:9,10-Dimethyl-1,2-benzanthracene; C025473:gamma-sitosterol; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; D000094062:Betulinic Acid