Green tea-mediated inhibition of aberrant DNA hypermethylation in prostate cancer

绿茶介导抑制前列腺癌异常 DNA 高甲基化

• 批准号: 7171726
• 负责人: ADAM R. KARPF
• 金额: $ 14.83万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7171726
• 关键词: DNA; epigenetics; methylation; neoplasm /cancer; prostate neoplasms; tea

DESCRIPTION (provided by applicant): A role for green tea in the prevention of human prostate cancer is supported by both epidemiological studies and laboratory investigations. Green tea extract (GTP) contains a number of bioactive polyphenolic compounds that account for its anti-carcinogenic properties. Previous studies have shown that oral infusion of GTP dramatically reduces tumor burden and metastasis in a spontaneous autochthonous transgenic mouse model of prostate cancer known as TRAMP. These data support the use of the TRAMP model to examine the molecular mechanisms involved in GTP-mediated prostate cancer chemoprevention. Recently, green tea polyphenols were identified as potent inhibitors of DNA methylation, a critical oncogenic mechanism. This suggests a novel and direct mechanism to account for the chemopreventive properties of GTP. Based on these data, it is hypothesized that DNA methylation changes are involved in the etiology of TRAMP prostate cancer, and that the chemopreventive effect of GTP in TRAMP is due to its ability to prevent or reverse aberrant DNA hypermethylation. To test this hypothesis, this proposal will: 1) Define the epigenetic changes coincident with prostate cancer progression in the TRAMP model; and 2) Determine the effect of GTP treatment on epigenetic parameters in TRAMP mice. Because prostate cancer has a long latency period and is most prevalent in men over the age of 65, dietary interventions that modestly delay progression time would have a profound impact on prostate cancer death rates. In this regard, GTP has the potential for significant utility as a chemopreventive agent in prostate cancer patients. Understanding the molecular mechanism(s) responsible for the activity of GTP is essential for the optimal design of prostate cancer chemoprevention trials and for the identification of novel molecular biomarkers to follow in clinical studies of GTP.

描述（由申请人提供）： 流行病学研究和实验室调查都支持绿茶在预防人类前列腺癌方面的作用。绿茶提取物 (GTP) 含有多种生物活性多酚化合物，具有抗癌特性。先前的研究表明，在自发性前列腺癌转基因小鼠模型（称为 TRAMP）中，口服 GTP 可以显着降低肿瘤负荷和转移。这些数据支持使用 TRAMP 模型来检查 GTP 介导的前列腺癌化学预防所涉及的分子机制。最近，绿茶多酚被确定为 DNA 甲基化（一种重要的致癌机制）的有效抑制剂。这提出了一种新颖且直接的机制来解释 GTP 的化学预防特性。基于这些数据，推测DNA甲基化变化与TRAMP前列腺癌的病因有关，并且GTP在TRAMP中的化学预防作用是由于其能够预防或逆转异常的DNA高甲基化。为了检验这一假设，该提案将： 1）定义 TRAMP 模型中与前列腺癌进展一致的表观遗传变化； 2) 确定 GTP 治疗对 TRAMP 小鼠表观遗传参数的影响。由于前列腺癌的潜伏期很长，并且在 65 岁以上的男性中最为常见，因此适度延迟进展时间的饮食干预将对前列腺癌的死亡率产生深远的影响。在这方面，GTP 作为前列腺癌患者的化学预防剂具有重要的用途。了解导致 GTP 活性的分子机制对于前列腺癌化学预防试验的优化设计以及鉴定 GTP 临床研究中遵循的新型分子生物标志物至关重要。