Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.
Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.
J Cell Mol Med. 2017 Nov;21(11):2837-2851. doi: 10.1111/jcmm.13197. Epub 2017 May 19.
It is supposed that plant functional foods, rich in phytochemicals, may potentially have preventive effects in carcinogenesis. In this study, the anticancer effects of cloves in the in vivo and in vitro mammary carcinoma model were assessed. Dried flower buds of cloves (CLOs) were used at two concentrations of 0.1% and 1% through diet during 13 weeks after the application of chemocarcinogen. After autopsy, histopathological and immunohistochemical analyses of rat mammary carcinomas were performed. Moreover, in vitro evaluation using MCF-7 cells was carried out. Dietary administered CLO caused the dose-dependent decrease in tumour frequency by 47.5% and 58.5% when compared to control. Analysis of carcinoma cells in animals showed bcl-2, Ki67, VEGFA, CD24 and CD44 expression decrease and Bax, caspase-3 and ALDH1 expression increase after high-dose CLO administration. MDA levels were substantially decreased in rat carcinomas in both CLO groups. The evaluation of histone modifications revealed increase in lysine trimethylations and acetylations (H4K20me3, H4K16ac) in carcinomas after CLO administration. TIMP3 promoter methylation levels of CpG3, CpG4, CpG5 islands were altered in treated cancer cells. An increase in total RASSF1A promoter methylation (three CpG sites) in CLO 1 group was found. In vitro studies showed antiproliferative and pro-apoptotic effects of CLO extract in MCF-7 cells (analyses of cytotoxicity, Brdu, cell cycle, annexin V/PI, caspase-7, Bcl-2 and mitochondrial membrane potential). This study showed a significant anticancer effect of clove buds in the mammary carcinoma model in vivo and in vitro.
据推测，富含植物化学物质的植物功能性食品可能具有潜在的抗癌作用。在这项研究中，评估了丁香在体内和体外乳腺癌模型中的抗癌作用。使用两种浓度（0.1%和 1%）的丁香干花蕾（CLOs）通过饮食在应用化学致癌剂后 13 周内给药。尸检后，对大鼠乳腺癌进行了组织病理学和免疫组织化学分析。此外，还进行了 MCF-7 细胞的体外评估。与对照组相比，饮食给予 CLO 导致肿瘤频率呈剂量依赖性降低，分别为 47.5%和 58.5%。对动物中癌细胞的分析表明，高剂量 CLO 给药后 bcl-2、Ki67、VEGFA、CD24 和 CD44 表达减少，Bax、caspase-3 和 ALDH1 表达增加。在两个 CLO 组的大鼠癌中，MDA 水平均显著降低。组蛋白修饰的评估显示，给药后 CLO 可增加赖氨酸三甲基化和乙酰化（H4K20me3、H4K16ac）。TIMP3 启动子 CpG3、CpG4、CpG5 岛的甲基化水平在处理的癌细胞中发生改变。在 CLO1 组中发现总 RASSF1A 启动子甲基化（三个 CpG 位点）增加。体外研究显示 CLO 提取物在 MCF-7 细胞中具有抗增殖和促凋亡作用（细胞毒性、Brdu、细胞周期、Annexin V/PI、caspase-7、Bcl-2 和线粒体膜电位分析）。本研究表明，丁香花蕾在体内和体外乳腺癌模型中具有显著的抗癌作用。
