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Inhibitory Effect of Apigenin, a Plant Flavonoid, on Epidermal Ornithine Decarboxylase and Skin Tumor Promotion in Mice¹

Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68105

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 µmol. Two tumorigenesis studies were conducted. In the first study, 20 µmol 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 µmol of apigenin were used. The papilloma incidence for 0, 5, and 20 µmol 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 tumorbearing animal and the ratio of carcinomas/papillomas in two apigenintreated 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.

¹ The Eppley Institute is a National Cancer Institute-sponsored Laboratory Cancer Research Center supported in part by Grant CA36727 and is an American Cancer Society Cancer Prevention Center supported in part by Grant SIG-16.

² To whom requests for reprints should be addressed, at Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, NE 68105-1065.

Received 2/16/89. Revised 9/27/89. Accepted 10/25/89.

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