Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Mol Nutr Food Res. 2014 Mar;58(3):457-65. doi: 10.1002/mnfr.201300345. Epub 2013 Oct 1.
Colorectal cancer is an important health problem across the world. Here, we investigated the possible antiproliferative/proapoptotic effects of bromelain (from the pineapple stem Ananas comosus L., family Bromeliaceae) in a human colorectal carcinoma cell line and its potential chemopreventive effect in a murine model of colon cancer.
Proliferation and apoptosis were evaluated in human colon adenocarcinoma (Caco-2) cells by the (3) H-thymidine incorporation assay and caspase 3/7 activity measurement, respectively. Extracellular signal-related kinase (ERK) and Akt expression were evaluated by Western blot analysis, reactive oxygen species production by a fluorimetric method. In vivo, bromelain was evaluated using the azoxymethane murine model of colon carcinogenesis. Bromelain reduced cell proliferation and promoted apoptosis in Caco-2 cells. The effect of bromelain was associated to downregulation of pERK1/2/total, ERK, and pAkt/Akt expression as well as to reduction of reactive oxygen species production. In vivo, bromelain reduced the development of aberrant crypt foci, polyps, and tumors induced by azoxymethane.
Bromelain exerts antiproliferative and proapoptotic effects in colorectal carcinoma cells and chemopreventive actions in colon carcinogenesis in vivo. Bromelain-containing foods and/or bromelain itself may represent good candidates for colorectal cancer chemoprevention.
结直肠癌是全世界的一个重要健康问题。在这里,我们研究了菠萝茎(菠萝属,凤梨科)中的菠萝蛋白酶对人结肠癌细胞系的可能抗增殖/促凋亡作用及其在结肠癌小鼠模型中的潜在化学预防作用。
通过(3)H-胸腺嘧啶掺入测定法和半胱天冬酶 3/7 活性测定法分别评估人结肠腺癌(Caco-2)细胞的增殖和凋亡。通过 Western blot 分析评估细胞外信号调节激酶(ERK)和 Akt 的表达,通过荧光法评估活性氧的产生。在体内,使用氧化偶氮甲烷诱导的结肠癌小鼠模型评估了菠萝蛋白酶。菠萝蛋白酶可降低 Caco-2 细胞的增殖并促进其凋亡。菠萝蛋白酶的作用与下调 pERK1/2/总、ERK 和 pAkt/Akt 表达以及减少活性氧产生有关。在体内,菠萝蛋白酶可减少氧化偶氮甲烷诱导的异常隐窝病灶、息肉和肿瘤的发展。
菠萝蛋白酶对结直肠癌细胞具有抗增殖和促凋亡作用,并在体内结肠癌发生中具有化学预防作用。含菠萝蛋白酶的食物和/或菠萝蛋白酶本身可能是结直肠癌化学预防的良好候选物。