Anti-tumor-promoting action of FK506, a potent immunosuppressive agent.
The effect of FK506, a potent immunosuppressive agent, on 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13- acetate (TPA)-promoted skin papilloma formation was examined in CD-1 mice. A topical application of FK506 to mouse skin 15 min before each TPA treatment resulted in a dose-related inhibition of tumor formation. FK506 (1 mumol) almost completely inhibited tumor formation. This inhibitory effect of FK506 was not due to any damage inflicted on the initiated cells but due to its anti-tumor-promoting action. A topical application of FK506 also inhibited epidermal ornithine decarboxylase induction and skin inflammation caused by TPA in a dose-related manner. Significant inhibition by FK506 of TPA-induced endogenous protein phosphorylation in intact epidermal cells was not detected. These results indicate that FK506 inhibits TPA-induced tumor promotion at a step distal to the endogenous protein phosphorylation by TPA.
Jiang
H
H
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
Yamamoto
S
S
Nishikawa
K
K
Kato
R
R
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000517:prevention & control; D004790:Enzyme Induction; D005260:Female; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D065108:Ornithine Decarboxylase Inhibitors; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control; D010766:Phosphorylation; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D016559:Tacrolimus / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate
D016588:Anticarcinogenic Agents; D065108:Ornithine Decarboxylase Inhibitors; D015127:9,10-Dimethyl-1,2-benzanthracene; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; D016559:Tacrolimus