Harper Curt E, Patel Brijesh B, Wang Jun, Eltoum Isam A, Lamartiniere Coral A
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
Prostate. 2007 Oct 1;67(14):1576-89. doi: 10.1002/pros.20643.
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.
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.
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).
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.
前列腺癌（PCa）是美国男性癌症相关死亡的第二大主要原因。许多男性已在日常饮食中加入所谓的化学预防剂，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。我们假设，绿茶中的主要多酚表没食子儿茶素-3-没食子酸酯（EGCG）将通过调节性类固醇受体、生长因子信号传导和炎症途径在前列腺中发挥其化学预防作用。
给5周龄的雄性TRAMP（转基因腺癌小鼠前列腺）后代喂食AIN-76A饮食，并在自来水中添加0.06%的EGCG。在28周龄时处死动物，并对整个前列腺进行组织病理学评分。此外，在12周龄时处死动物，取出腹侧（VP）和背外侧（DLP）前列腺进行组织病理学评估、免疫印迹分析或酶联免疫吸附测定（ELISA）。
在本研究中，EGCG抑制前列腺癌的早期而非晚期。在VP中，EGCG显著降低细胞增殖、诱导凋亡，并降低雄激素受体（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激酶1和2（磷酸化ERK 1和2）、环氧化酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）。
AR的减弱、强效生长因子IGF-1的下调、炎症生物标志物的调节以及丝裂原活化蛋白激酶（MAPK）信号传导的降低可能有助于减少细胞增殖和诱导凋亡，从而为EGCG无毒抑制前列腺癌提供生化基础。
