Effects of 12-O-tetradecanoylphorbol-13-acetate and Mezerein on epidermal ornithine decarboxylase activity, isoproterenol-stimulated levels of cyclic adenosine 3':5'-monophosphate, and induction of mouse skin tumors in vivo

R. Allan Mufson, Susan M. Fischer, Greta L. Gleason, Thomas J. Slaga, A. K. Verma, R. K. Boutwell

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the antileukemic agent mezerein are diterpene esters of plant origin with certain structural similarities. Both compounds, when applied topically to mouse skin, were equipotent on a molar basis in inducing hyperplasia, inflammation, and ornithine decarboxylase activity, as well as in reducing cyclic adenosine 3':5'-monophosphate accumulation in response to β-adrener-gic stimulation. In contrast, mezerein was much less effective as a tumor promoter; the phorbol ester at 8.5 nmol/application yielded 78-fold more tumors than did 8.5 nmol mezerein per application to similarly initiated SENCAR mice. The superiority of the phorbol ester was nearly as great in CD-1 mice. These results suggest that although the induction of hyperplasia and ornithine decarboxylase activity may be necessary components of the carcinogenic process, they are not sufficient; 12-O-tetradecanoylphorbol-13-acetate must accomplish an essential event not accomplished by mezerein.

Original languageEnglish (US)
Pages (from-to)4791-4795
Number of pages5
JournalCancer Research
Volume39
Issue number12
StatePublished - Dec 1 1979
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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