Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester

Cancer Res. 1993 Mar 15;53(6):1255-61.


Caffeic acid phenethyl ester (CAPE) was isolated from propolis (a product of honeybee hives) that has been used in folk medicine as a potent antiinflammatory agent. CAPE is cytotoxic to tumor and virally transformed but not to normal cells. Our main goal was to establish whether CAPE inhibits the tumor promoter (12-O-tetradecanoylphorbol-13-acetate)-induced processes associated with carcinogenesis. Topical treatment of SENCAR mice with very low doses (0.1-6.5 nmol/topical treatment) of CAPE strongly inhibits the following 12-O-tetradecanoylphorbol-13-acetate-mediated oxidative processes that are considered essential for tumor promotion: (a) polymorphonuclear leukocyte infiltration into mouse skin and ears, as quantified by myeloperoxidase activity; (b) hydrogen peroxide (H2O2) production; and (c) formation of oxidized bases in epidermal DNA, as measured by 5-hydroxymethyluracil and 8-hydroxylguanine. A 0.5-nmol dose of CAPE suppresses the oxidative burst of human polymorphonuclear leukocytes by 50%. At higher doses (1-10 mumol), CAPE inhibits edema and ornithine decarboxylase induction in CD-1 and SENCAR mice. Interestingly, we discovered that 12-O-tetradecanoylphorbol-13-acetate-induced H2O2 production in bovine lenses also is inhibited by CAPE. Cumulatively, these findings point to CAPE as being a potent chemopreventive agent, which may be useful in combating diseases with strong inflammatory and/or oxidative stress components, i.e., various types of cancer and possibly cataract development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caffeic Acids / pharmacology*
  • Cattle
  • Cytotoxins / pharmacology*
  • DNA / metabolism
  • Edema / prevention & control
  • Female
  • Humans
  • Hydrogen Peroxide / metabolism
  • In Vitro Techniques
  • Lens, Crystalline / drug effects*
  • Lens, Crystalline / metabolism
  • Mice
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Ornithine Decarboxylase / biosynthesis
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology
  • Skin / drug effects*
  • Skin / metabolism
  • Tetradecanoylphorbol Acetate / toxicity*


  • Caffeic Acids
  • Cytotoxins
  • DNA
  • Hydrogen Peroxide
  • Ornithine Decarboxylase
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol
  • Tetradecanoylphorbol Acetate