Dietary intake of pterostilbene, a constituent of blueberries, inhibits the β-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats
Dietary intake of pterostilbene, a constituent of blueberries, inhibits the β-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats
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DOI：
10.1093/carcin/bgq004
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发表时间：
2010-07-01
期刊：
影响因子：
4.7
通讯作者：
Suh, Nanjoo
中科院分区：
文献类型：
--
作者：
Paul, Shiby;DeCastro, Andrew J.;Suh, Nanjoo
芪是一种存在于葡萄、浆果、花生和红酒中的植物化学物质。白藜芦醇（反式-3,5,4'-三羟基苯乙烯）是一种被广泛研究的二苯乙烯，已被证明在许多生物系统中具有抗氧化、抗炎、化学预防和抗衰老作用。我们之前报道了一种在蓝莓中发现的结构相关的二苯乙烯（trans-3,5-二甲氧基-4'-羟基二苯乙烯），可以有效减少注射偶氮氧甲烷（AOM）的大鼠结肠中异常隐窝灶形成的发生率和多样性。本研究旨在以结肠癌形成为终点，确定紫檀芪的化学预防潜力，并进一步评价紫檀芪在结肠癌发生中的机制作用。F344大鼠在7、8周龄时皮下注射2次AOM，连续饲喂对照或40 pm紫檀芪日粮45周。综合分析表明，紫檀芪可降低非侵袭性腺癌结肠肿瘤的多样性，降低增殖细胞核抗原，下调β -catenin和cyclin D1的表达。紫檀芪可降低粘膜促炎细胞因子、肿瘤坏死因子- α、白细胞介素-1 β和白细胞介素-4的水平。来自紫菀芪类动物的结肠肿瘤显示炎症标志物的表达降低以及核因子- kappab途径的关键分子磷酸化-p65的核染色。在HT-29细胞中，紫芪可降低β -catenin、cyclin D1和c-MYC的蛋白水平，改变β -catenin的细胞定位，抑制p65的磷酸化。我们关于紫檀芪在体内和体外抑制结肠肿瘤发生、细胞增殖以及关键炎症标志物方面的数据表明，紫檀芪在结肠癌预防方面具有潜在的应用前景。
Stilbenes are phytochemicals present in grapes, berries, peanuts and red wine. A widely studied stilbene, resveratrol (trans-3,5,4'-trihydroxystilbene), has been shown to exert antioxidant, anti-inflammatory, chemopreventive and antiaging effects in a number of biological systems. We reported earlier that pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene), a structurally related stilbene found in blueberries, was effective in reducing the incidence and multiplicity of aberrant crypt foci formation in the colon of rats injected with azoxymethane (AOM). Our present study was to identify the chemopreventive potential of pterostilbene with colonic tumor formation as an end point and further to evaluate the mechanistic action of pterostilbene during colon carcinogenesis. F344 rats were given two AOM injections subcutaneously when they were 7 and 8 weeks old and continuously fed the control or 40 p.p.m. pterostilbene diet for 45 weeks. Overall analyses indicated that pterostilbene reduced colon tumor multiplicity of non-invasive adenocarcinomas, lowered proliferating cell nuclear antigen and downregulated the expression of beta-catenin and cyclin D1. Pterostilbene decreased mucosal levels of the proinflammatory cytokines, tumor necrosis factor-alpha, interleukin (IL)-1 beta and IL-4. Colon tumors from pterostilbene-fed animals showed reduced expression of inflammatory markers as well as nuclear staining for phospho-p65, a key molecule in the nuclear factor-kappaB pathway. In HT-29 cells, pterostilbene reduced the protein levels of beta-catenin, cyclin D1 and c-MYC, altered the cellular localization of beta-catenin and inhibited the phosphorylation of p65. Our data with pterostilbene in suppressing colon tumorigenesis, cell proliferation as well as key inflammatory markers in vivo and in vitro suggest the potential use of pterostilbene for colon cancer prevention.