Frenkel K, Wei H, Bhimani R, Ye J, Zadunaisky J A, Huang M T, Ferraro T, Conney A H, Grunberger D
Department of Environmental Medicine, New York University Medical Center, New York 10016-6451.
Cancer Res. 1993 Mar 15;53(6):1255-61.
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.
咖啡酸苯乙酯（CAPE）是从蜂胶（蜜蜂蜂巢的产物）中分离出来的，蜂胶在民间医学中一直被用作一种强效抗炎剂。CAPE对肿瘤细胞和病毒转化细胞具有细胞毒性，但对正常细胞无毒性。我们的主要目标是确定CAPE是否能抑制肿瘤启动子（12-O-十四烷酰佛波醇-13-乙酸酯）诱导的与致癌作用相关的过程。用极低剂量（0.1-6.5纳摩尔/局部治疗）的CAPE对SENCAR小鼠进行局部治疗，能强烈抑制以下被认为对肿瘤促进至关重要的12-O-十四烷酰佛波醇-13-乙酸酯介导的氧化过程：（a）通过髓过氧化物酶活性定量的多形核白细胞浸润到小鼠皮肤和耳朵中；（b）过氧化氢（H2O2）的产生；（c）通过5-羟甲基尿嘧啶和8-羟基鸟嘌呤测量的表皮DNA中氧化碱基的形成。0.5纳摩尔剂量的CAPE可使人类多形核白细胞的氧化爆发抑制50%。在较高剂量（1-10微摩尔）时，CAPE可抑制CD-1和SENCAR小鼠的水肿和鸟氨酸脱羧酶诱导。有趣的是，我们发现CAPE也能抑制12-O-十四烷酰佛波醇-13-乙酸酯诱导的牛晶状体中H2O2的产生。总的来说，这些发现表明CAPE是一种强效的化学预防剂，可能有助于对抗具有强烈炎症和/或氧化应激成分的疾病，即各种类型的癌症以及可能的白内障发展。
