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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.

Abstract
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.
AuthorsT Nakadate, S Yamamoto, E Aizu, R Kato
JournalPharmacology (Pharmacology) Vol. 32 Issue 3 Pg. 167-75 ( 1986) ISSN: 0031-7012 [Print] Switzerland
PMID3083437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Calmodulin
  • Lyngbya Toxins
  • Phorbols
  • Sulfonamides
  • teleocidins
  • W 7
  • Protein Kinase C
  • Ornithine Decarboxylase
  • Tetradecanoylphorbol Acetate
  • Calcium
Topics
  • Animals
  • Calcium (pharmacology)
  • Calmodulin (antagonists & inhibitors)
  • Enzyme Induction (drug effects)
  • Female
  • Lyngbya Toxins (toxicity)
  • Mice
  • Mice, Inbred Strains
  • Ornithine Decarboxylase (biosynthesis)
  • Papilloma (chemically induced)
  • Phorbols
  • Protein Kinase C (analysis)
  • Skin (drug effects, enzymology)
  • Skin Neoplasms (chemically induced, prevention & control)
  • Sulfonamides (pharmacology)
  • Tetradecanoylphorbol Acetate

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