Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice.
This investigation studied the effect of topical application of apigenin on skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) in SENCAR mice. Apigenin was a potent inhibitor of epidermal ornithine decarboxylase induction by TPA in a dose-dependent manner from 1 to 20 mumol. Two tumorigenesis studies were conducted. In the first study, 20 mumol of apigenin was applied topically and no effect on body weight was observed. By week 33 after DMBA initiation, 48% of DMBA/TPA-treated mice developed carcinomas, while none occurred in DMBA/apigenin/TPA-treated groups. In the second study, doses of 5 and 20 mumol of apigenin were used. The papilloma incidence for 0, 5, and 20 mumol apigenin at 26 weeks after DMBA was 93.3, 58, and 39.3%, and papilloma numbers per mouse were 7.5, 2.5, and 1.8, respectively. Apigenin prolonged by 3 weeks the latency period of tumor appearance. In addition, apigenin significantly inhibited the incidence of carcinoma and the numbers of carcinomas. The incidence of carcinomas per tumor-bearing animal and the ratio of carcinomas/papillomas in two apigenin-treated groups decreased although there were no significant differences between the three groups. These data indicate that apigenin inhibited skin papillomas and showed the tendency to decrease conversion of papillomas to carcinomas.
Wei
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Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68105.
Tye
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Bresnick
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Birt
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D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D020843:Chamomile; D003043:Cocarcinogenesis; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004817:Epidermis / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology*; D051379:Mice; D009822:Oils, Volatile / Q000494:pharmacology*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010212:Papilloma / Q000139:chemically induced; D010946:Plants, Medicinal; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate
D005419:Flavonoids; D009822:Oils, Volatile; D015127:9,10-Dimethyl-1,2-benzanthracene; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate