咖啡酸苯乙酯（CAPE）对12-O-十四烷酰佛波醇-13-乙酸酯诱导的小鼠皮肤肿瘤促进作用以及对HeLa细胞中DNA、RNA和蛋白质合成的抑制作用。

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.

作者信息

Huang M T, Ma W, Yen P, Xie J G, Han J, Frenkel K, Grunberger D, Conney A H

机构信息

Department of Chemical Biology, College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08855-0789, USA.

出版信息

Carcinogenesis. 1996 Apr;17(4):761-5. doi: 10.1093/carcin/17.4.761.

DOI:10.1093/carcin/17.4.761

PMID:8625488

Abstract

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[a]anthracene (DMBA) inhibited 12-O-tetradecanoylphorbol-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 of DMBA 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 10(4) 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 microM 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 culture HeLa cells.

摘要

将蜂胶的一种成分咖啡酸苯乙酯（CAPE）局部涂抹于先前用7,12-二甲基苯并[a]蒽（DMBA）启动的CD-1小鼠背部，可抑制12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的肿瘤促进作用以及表皮DNA中5-羟甲基-2'-脱氧尿苷（HMdU）的形成。每周两次给先前用200 nmol DMBA启动的小鼠局部涂抹5 nmol TPA，持续20周，每只小鼠产生18.8个皮肤乳头状瘤。每周两次将1、10、100或3000 nmol的CAPE与5 nmol TPA一起局部涂抹20周，每只小鼠的皮肤乳头状瘤数量分别减少24%、30%、45%或70%，每只小鼠的肿瘤大小分别减少42%、66%、53%或74%。每周两次给先前用DMBA启动的小鼠局部涂抹5 nmol TPA，持续20周，表皮DNA中每10(4)个正常碱基平均产生12.6个HMdU残基。每周两次将1、10、100或3000 nmol的CAPE与5 nmol TPA一起局部涂抹20周，给DMBA启动的小鼠使用后，表皮DNA中HMdU水平降低40 - 93%。在培养的HeLa细胞中体外添加1.25、2.5、5、10或20 μM的CAPE，DNA合成分别被抑制32%、44%、66%、79%或95%，RNA合成分别被抑制39%、43%、58%、64%或75%，蛋白质合成分别被抑制29%、30%、37%、32%或47%。结果表明，CAPE对TPA诱导的肿瘤促进作用以及TPA诱导的小鼠皮肤DNA中HMdU的形成具有强大的抑制作用，并且CAPE对培养的HeLa细胞中DNA、RNA和蛋白质的合成具有抑制作用。