Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity and tumor promotion by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) in mouse skin.
N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) inhibited epidermal ornithine decarboxylase (ODC) induction caused either by 12-O-tetradecanoylphorbol-13-acetate (TPA) or teleocidin in CD-1 mice. Inhibitory effect of W-7 on TPA-caused ODC induction was also observed in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated skin and even after repetitive TPA treatment. TPA-induced skin tumor promotion was also suppressed by W-7. Meanwhile, W-7 showed only slight inhibitory effects on calcium-activated, phospholipid-dependent protein kinase (protein kinase C) activity of mouse epidermis stimulated either by Ca2+ or TPA in the presence of phosphatidylserine. Thus, it is unlikely that the anti-ODC-inducing and anti-tumor-promoting actions of W-7 are due to its inhibitory effect on protein kinase C. It may be possible that a calmodulin-mediating process is involved in the mechanism of epidermal ODC induction and tumor promotion caused by tumor promoters such as TPA and teleocidin.
Nakadate
T
T
Yamamoto
S
S
Aizu
E
E
Kato
R
R
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008235:Lyngbya Toxins / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010212:Papilloma / Q000139:chemically induced*; D010704:Phorbols; D011493:Protein Kinase C / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D013449:Sulfonamides / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate
D002147:Calmodulin; D008235:Lyngbya Toxins; D010704:Phorbols; D013449:Sulfonamides; C022176:teleocidins; C017967:W 7; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium