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 | K Frenkel, H Wei, R Bhimani, J Ye, J A Zadunaisky, M T Huang, T Ferraro, A H Conney, D Grunberger |
Journal | Cancer research
(Cancer Res)
Vol. 53
Issue 6
Pg. 1255-61
(Mar 15 1993)
ISSN: 0008-5472 [Print] United States |
PMID | 7680281
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Caffeic Acids
- Cytotoxins
- DNA
- Hydrogen Peroxide
- Ornithine Decarboxylase
- caffeic acid phenethyl ester
- Phenylethyl Alcohol
- Tetradecanoylphorbol Acetate
|
Topics |
- Animals
- Caffeic Acids
(pharmacology)
- Cattle
- Cytotoxins
(pharmacology)
- DNA
(metabolism)
- Edema
(prevention & control)
- Female
- Humans
- Hydrogen Peroxide
(metabolism)
- In Vitro Techniques
- Lens, Crystalline
(drug effects, metabolism)
- Mice
- Neutrophils
(drug effects, metabolism)
- Ornithine Decarboxylase
(biosynthesis)
- Phenylethyl Alcohol
(analogs & derivatives, pharmacology)
- Skin
(drug effects, metabolism)
- Tetradecanoylphorbol Acetate
(toxicity)
|