Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable
Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable
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DOI：
10.1093/carcin/bgl049
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发表时间：
2006-10-01
期刊：
影响因子：
4.7
通讯作者：
Kong, Ah-Ng Tony
中科院分区：
文献类型：
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作者：
Hu, Rong;Khor, Tin Oo;Kong, Ah-Ng Tony
萝卜硫素（SFN）是一种异硫氰酸酯，广泛存在于十字花科蔬菜中，在花椰菜和花椰菜中含量特别高。它已被证明是一种有效的抑制剂，对某些致癌物质诱发的癌症在啮齿动物。在这里，我们研究了SFN在ApcMin/+小鼠模型中的化学预防功效。ApcMin/+小鼠用补充有两种不同剂量水平的SFN（300和600 p. p.m.）三个星期。我们的研究结果清楚地表明，ApcMin/+小鼠喂养SFN补充饮食发展显着更少，更小的息肉，更高的凋亡和更低的增殖指数，在其小肠，在SFN剂量依赖性的方式。此外，腺瘤的免疫组织化学（IHC）染色表明SFN显著抑制磷酸化c-Jun N-末端激酶（p-JNK）、磷酸化细胞外信号调节激酶（p-ERK）和磷酸化Akt（p-Akt）的表达，这些蛋白在ApcMin/+小鼠的腺瘤中高度表达。相反，两个重要的Wnt信号通路的生物标志物，β-连环蛋白和细胞周期蛋白-D1的表达不受SFN治疗的影响。使用LC-MS测量小肠中的SFN及其代谢物SFN-GSH表明，需要3至30 nmol/g的浓度来预防或延迟ApcMin/+小鼠胃肠道中的腺瘤形成。
Sulforaphane (SFN) is an isothiocyanate that is present abundantly in widely consumed cruciferous vegetables and has a particularly high content in broccoli and cauliflower. It has been shown to be an effective inhibitor of some carcinogen-induced cancers in rodents. Here, we investigated the chemopreventive efficacy of SFN in the ApcMin/+ mouse model. ApcMin/+ mice were fed with diet supplemented with two different dose levels of SFN (300 and 600 p.p.m.) for 3 weeks. Our results clearly demonstrated that ApcMin/+ mice fed with SFN-supplemented diet developed significantly less and smaller polyps with higher apoptotic and lower proliferative indices in their small intestine, in a SFN dose-dependent manner. In addition, immunohistochemical (IHC) staining of the adenomas indicated that SFN significantly suppressed the expression of phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated extracellular signal-regulated kinases (p-ERK) and phosphorylated-Akt (p-Akt), which were found to be highly expressed in the adenomas of ApcMin/+ mice. In contrast, expression of two important biomarkers of the Wnt signaling pathway, beta-catenin and cyclin-D1 was unaffected by SFN treatment. Measurement of SFN and its metabolite SFN-GSH in the small intestine using LC-MS indicates that the concentrations between 3 and 30 nmol/g are required to prevent, or retard adenoma formation in the gastrointestinal tract of ApcMin/+ mice.