Journal Article

Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-<i>O</i>-tetradecanoylphorbol-13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA, RNA and protein in HeLa cells

Mou-Tuan Huang, Wei Ma, Patricia Yen, Jian-Guo Xie, Jingkang Han, Krystyna Frenkel, Dezider Grunberger and Allan H. Conney

in Carcinogenesis

Volume 17, issue 4, pages 761-765
Published in print April 1996 | ISSN: 0143-3334
Published online April 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.4.761
Inhibitory effects of caffeic acid phenethyl ester (CAPE) on
                        12-O-tetradecanoylphorbol-13-acetate-induced tumor
                    promotion in mouse skin and the synthesis of DNA, RNA and protein in HeLa
                    cells

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Topical application of caffeic acid phenethyl ester (CAPE), a constituent of the propolis of honeybee hives, to the backs of CD-1 mice previously initiated with 7, 12-dimethylbenz[α]anthracene (DMBA) inhibited 12-O-tetra-decanoylphorbol-13-acetate (TPA)-induced tumor promotion and the formation of 5-hydroxymethyl-2'-deoxyuridine (HMdU) in epidermal DNA. Topical application of 5 nmol TPA twice weekly for 20 weeks to mice previously initiated with 200 nmol ofDMBA resulted in 18.8 skin papillomas per mouse. Topical application of 1, 10, 100 or 3000 nmol of CAPE together with 5 nmol of TPA twice a week for 20 weeks inhibited the number of skin papillomas per mouse by 24, 30, 45 or 70%, respectively, and tumor size per mouse was decreased by 42, 66, 53 or 74%, respectively. Topical application of 5 nmol of TPA twice weekly for 20 weeks to mice previously initiated with DMBA produced an average of 12.6 HMdU residues per 104 normal bases in epidermal DNA. Topical application of 1, 10, 100 or 3000 nmol of CAPE with 5 nmol of TPA twice weekly for 20 weeks to DMBA-initiated mice decreased the level of HMdU in epidermal DNA by 40-93%. The in vitro addition of 1.25, 2.5, 5, 10 or 20 μM CAPE to cultured HeLa cells inhibited the synthesis of DNA by 32, 44, 66, 79 or 95%, respectively, the synthesis of RNA was inhibited by 39, 43, 58, 64 or 75%, respectively, and the synthesis of protein was inhibited by 29, 30, 37, 32 or 47%, respectively. The results indicate a potent inhibitory effect of CAPE on TPA-induced tumor promotion and TPA-induced formation of HMdU in DNA of mouse skin as well as an inhibitory effect of CAPE on the synthesis of DNA, RNA and protein in cultured HeLa cells.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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