Chemoprevention of familial adenomatous polyposis in ApcMin/+ mice by phenethyl isothiocyanate (PEITC)
Chemoprevention of familial adenomatous polyposis in ApcMin/+ mice by phenethyl isothiocyanate (PEITC)
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DOI：
10.1002/mc.20390
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发表时间：
2008-05-01
影响因子：
4.6
通讯作者：
Kong, Ah-Ng Tony
中科院分区：
文献类型：
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作者：
Khor, Tin Oo;Cheung, William Ka Lung;Kong, Ah-Ng Tony
异硫氰酸苯乙酯（PEITC）是一种异硫氰酸酯，是西洋菜和其他十字花科蔬菜的主要成分。其化学预防潜力先前已在各种啮齿动物癌症模型中显示。在这项研究中，我们研究了PEITC在Apc（Min/+）小鼠模型中的化学预防功效。Apc（Min/+）小鼠饲喂添加0.05% PEITC的饲料3周。我们的结果清楚地表明，与用标准AIN-76 A饮食喂养的小鼠相比，用PEITC补充的饮食喂养的Apc（Min/+）小鼠产生显著更少（减少31.7%）和更小的息肉。随后使用蛋白质印迹法的机制研究表明，PEITC抑制腺瘤生长与细胞凋亡（切割的半胱天冬酶-3，半胱天冬酶-7和PARP）的增加有关。治疗还导致细胞周期相关生物标志物的抑制，如细胞周期蛋白（D1，A和E）和p21的激活。然而，PEITC对p-Erk、p-JNK和p-p38的表达没有影响。总之，我们的研究结果表明，PEITC是一种有效的天然膳食化合物，用于胃肠道癌症的化学预防。其作用机制可能包括诱导细胞凋亡和细胞周期阻滞。(c)2007 Wiley-Liss，Inc.
Phenethyl isothiocyanate (PEITC) is an isothiocyanate which is a major constituent of watercress and other cruciferous vegetables. Its chemopreventive potential has been previously shown in various rodent models of cancer. In this study, we investigated the chemopreventive efficacy of PEITC in the Apc(Min/+) mouse model. Apc(Min/+) mice were fed with diet supplemented with 0.05% of PEITC for 3-wk. Our results clearly demonstrated that Apc(Min/+) mice fed with PEITC supplemented diet developed significantly less (31.7% reduction) and smaller polyps in comparison to mice fed with the standard AIN-76A diet. Subsequent mechanistic study using Western blotting shows that inhibition of growth of adenomas by PEITC is associated with increase of apoptosis (cleaved-caspase-3, -caspase-7, and PARP). Treatments also led to the inhibition of cell cycle-related biomarkers such as the cyclins (D1, A, and E) and activation of p21. However, PEITC has no effect on the expression of p-Erk, p-JNK or p-p38. In conclusion, our results demonstrate that PEITC is a potent natural dietary compound for chemoprevention of gastrointestinal cancers. Its mechanism of actions may include induction of apoptosis and cell cycle arrest. (c) 2007 Wiley-Liss, Inc.