Epigallocatechin-3-gallate suppresses early stage, but not late stage prostate cancer in TRAMP mice: Mechanisms of action
Epigallocatechin-3-gallate suppresses early stage, but not late stage prostate cancer in TRAMP mice: Mechanisms of action
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DOI：
10.1002/pros.20643
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发表时间：
2007-10-01
期刊：
影响因子：
2.8
通讯作者：
Lamartiniere, Coral A.
中科院分区：
文献类型：
--
作者：
Harper, Curt E.;Patel, Brijesh B.;Lamartiniere, Coral A.
背景资料。前列腺癌(PCA)是美国男性癌症相关死亡的第二大原因。许多男性在日常饮食中加入所谓的化学预防药物，试图延缓前列腺癌的早期发病。绿茶多酚就是这样一种物质，已被证明对皮肤癌、乳腺癌和前列腺癌具有化学预防作用。我们推测，绿茶中发现的主要多酚-表没食子儿茶素没食子酸酯(EGCG)将通过调节性类固醇受体、生长因子信号和炎症途径在前列腺发挥化学预防作用。方法：5周龄雄性流浪鼠(转基因前列腺癌小鼠)子代在自来水中添加AIN-76A饲料和0.06%的EGCG。动物在28周龄时被处死，并对整个前列腺进行组织病理学评分。此外，动物在12周龄时被处死，取出前列腺腹侧(VP)和背侧(DLP)进行组织病理学评估和免疫印迹分析。结果在本研究中，EGCG抑制了早期但不是晚期的前列腺癌。在VP中，EGCG显著抑制细胞增殖，诱导细胞凋亡，降低雄激素受体(AR)、胰岛素样生长因子-1(IGF-1)、IGF-1受体(IGF-1R)、磷酸化细胞外信号调节蛋白1和2(Pho-ERKs1和2)、环氧合酶-2(COX-2)和诱导型一氧化氮合酶(INOS)。而MAPK信号通路的减少可能有助于抑制细胞增殖和诱导细胞凋亡，从而为EGCG无毒抑制PCa提供了生化基础。
BACKGROUND. Prostate cancer (PCa) is the second leading cause of cancer-related death in men in the United States. Many men have implemented purported chemopreventive agents into their daily diet in an attempt to delay the early onset of a PCa. Green tea polyphenols, one such agent, has been shown to be chemopreventive in skin, breast, and prostate cancers. We hypothesized that Epigallocatechin-3-Gallate (EGCG), the major polyphenol found in green tea, will exert its chemopreventive effect in the prostate via regulation of sex steroid receptor, growth factor-signaling, and inflammatory pathways.METHODS. Five-week-old male TRAMP (Transgenic Adenocarcinoma Mouse Prostate) offspring were fed AIN-76A diet and 0.06% EGCG in tap water. Animals were sacrificed at 28 weeks of age and the entire prostates were scored histopathologically. In addition, animals were sacrificed at 12 weeks of age and ventral (VP) and dorsolateral (DLP) prostates were removed for histopathological evaluation and immunoblot analyses or ELISA.RESULTS. EGCG, inhibited early but not late stage PCa in the current study. In the VP, EGCG significantly reduced cell proliferation, induced apoptosis, and decreased androgen receptor (AR), insulin-like growth factor-1 (IGF-1), IGF-1 receptor (IGF-1R), phospho-extracellular signal-regulated kinases 1 and 2 (phospho-ERKs 1 and 2), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS).CONCLUSIONS. The attenuation of the AR, the down-regulation of potent growth factor IGF-1, modulation of inflammation biomarkers, and decrease in the MAPK signaling may contribute to the reduction in cell proliferation and induction of apoptosis and hence provide a biochemical basis for EGCG suppressing PCa without toxicity.