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

Teruo Nakadate, Satoshi Yamamoto, Eriko Aizu, Ryuichi Kato

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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.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
JournalPharmacology
Volume32
Issue number3
DOIs
Publication statusPublished - 1986 Jan 1

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Keywords

  • 12-O-Tetradecanoylphorbol-13-acetate
  • Calmodulin
  • N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
  • Ornithine decarboxylase
  • Protein kinase C
  • Teleocidin

ASJC Scopus subject areas

  • Pharmacology

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