title: Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester.
abstract: 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.
authors.affiliation: Department of Environmental Medicine, New York University Medical Center, New York 10016-6451.
authors.forename: K
authors.initials: K
authors.lastname: Frenkel
authors.forename: H
authors.initials: H
authors.lastname: Wei
authors.forename: R
authors.initials: R
authors.lastname: Bhimani
authors.forename: J
authors.initials: J
authors.lastname: Ye
authors.forename: J A
authors.initials: JA
authors.lastname: Zadunaisky
authors.forename: M T
authors.initials: MT
authors.lastname: Huang
authors.forename: T
authors.initials: T
authors.lastname: Ferraro
authors.forename: A H
authors.initials: AH
authors.lastname: Conney
authors.forename: D
authors.initials: D
authors.lastname: Grunberger
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D002417:Cattle; D003603:Cytotoxins / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004487:Edema / Q000517:prevention & control; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: D002109:Caffeic Acids; D003603:Cytotoxins; D004247:DNA; D006861:Hydrogen Peroxide; D009955:Ornithine Decarboxylase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D013755:Tetradecanoylphorbol Acetate