Oral Consumption of Green Tea Polyphenols Inhibits Insulin-Like Growth Factor-I–Induced Signaling in an Autochthonous Mouse Model of Prostate Cancer

作者：Vaqar Mustafa Adhami, Imtiaz Ahmad Siddiqui, Nihal Ahmad, Sanjay Gupta, Hasan Mukhtar · 发表于：Cancer Research · 年份：2004 · DOI：10.1158/0008-5472.can-04-2840 · 被引用次数：297 · 研究领域：Tea Polyphenols and Effects、Growth Hormone and Insulin-like Growth Factors、Cancer, Hypoxia, and Metabolism

We earlier demonstrated that oral infusion of green tea polyphenols inhibits development and progression of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Evidence indicates that elevated levels of IGF-I with concomitant lowering of IGF binding protein (IGFBP)-3 are associated with increased risk for prostate cancer development and progression. In this study, we examined the role of IGF/IGFBP-3 signaling and its downstream and other associated events during chemoprevention of prostate cancer by green tea polyphenols in TRAMP mice. Our data demonstrated an increase in the levels of IGF-I, phosphatidylinositol 3'-kinase, phosphorylated Akt (Thr-308), and extracellular signal-regulated kinase 1/2 with concomitant decrease in IGFBP-3 in dorso-lateral prostate of TRAMP mice during the course of cancer progression, i.e., as a function of age. Continuous green tea polyphenol infusion for 24 weeks to these mice resulted in substantial reduction in the levels of IGF-I and significant increase in the levels of IGFBP-3 in the dorso-lateral prostate. This modulation of IGF/IGFBP-3 was found to be associated with an inhibition of protein expression of phosphatidylinositol 3'-kinase, phosphorylated forms of Akt (Thr-308) and extracellular signal-regulated kinase 1/2. Furthermore, green tea polyphenol infusion resulted in marked inhibition of markers of angiogenesis and metastasis most notably vascular endothelial growth factor, urokinase plasminogen activ...