EGCG and Omega-3 Fatty Acids Impact on Fatty Acid Synthase Activity in the Prosta

描述（由申请人提供）：前列腺特异性抗原（PSA）筛查极大地提高了我们识别前列腺癌风险男性和早期诊断这种疾病的能力。但是，由于PSA升高而接受前列腺活检的男性中，只有大约25%被诊断为前列腺癌。对于那些活检阴性的男性，他们对前列腺癌风险的认识已经大大提高，并且可能强烈希望确定降低最终发展这种疾病风险的方法。这些男性中的许多人可能会寻求补充和替代药物（CAM），试图改变他们患前列腺癌的风险。许多CAM化合物，包括欧米茄-3脂肪酸（omega-3 FA）和绿色茶儿茶素已被假设为降低前列腺癌的风险。然而，重要的是要了解它们如何发挥作用以减缓或抑制前列腺癌发生的生物学机制。一种特定的生物途径是脂肪酸合成酶（FAS）途径，其可以被ω-3 FA和特定的绿色茶儿茶素、表没食子儿茶素-3-没食子酸酯（EGCG）改变。FAS是一种脂肪生成多酶，催化脂肪酸从头合成的最后一步，已被证明在前列腺癌发生中高度表达，并与更严重的疾病相关。体外和体内研究表明，EGCG和omega-3 FA均可抑制FAS的过度表达。 我们的主要目标或建议是阐明在前列腺癌高风险的男性中，一种潜在的生物学机制，即单独使用EGCG或与omega-3 FA联合使用，可能会改变细胞组成和生长，从而降低前列腺癌的总体风险。在拟定的GCRC申办的随机安慰剂对照研究中，我们将评估EGCG和EGCG + omega-3 FA对接受重复前列腺活检的男性bengin、肿瘤前和肿瘤前列腺组织中FAS表达、FAS活性、细胞增殖和凋亡的独立和联合作用。 这项研究的结果将提供一些第一个证据，将观察到的可通过饮食改变的因素（主要是EGCG和omega-3 FA）与影响前列腺癌发生的特定生物学机制（FAS途径）之间的关联联系起来。阐明可能受饮食调节的单一致癌途径可能为靶向预防治疗提供新的令人兴奋的机会。

DESCRIPTION (provided by applicant): Prostate specific antigen (PSA) screening has vastly improved our ability to identify men at risk of prostate cancer and diagnose this disease at an early stage. But, of men who undergo prostate biopsy due to elevated PSA, only approximately 25% are diagnosed with prostate cancer. For those men with a negative biopsy, the awareness of their risk of prostate cancer has been raised dramatically, and there may be a strong desire to identify methods to reduce their risk of ultimately developing this disease. Many of these men may seek out complementary and alternative medicines (CAM) in an attempt to alter their risk of prostate cancer. A number of CAM compounds, including omega-3 fatty acids (omega-3 FA) and green tea catechins have been hypothesized to reduce prostate cancer risk. However, it is important to understand the biologic mechanism underlying how they may function to slow or inhibit prostate carcinogenesis. One particular biologic pathway, which may be altered by both omega -3 FA and the specific green tea catechin, epigallocatechin-3-gallate (EGCG), is the fatty acid synthase (FAS) pathway. FAS, a lipogenic multienzyme that catalyzes the final step in de novo fatty acid synthesis, has been shown to be highly expressed in prostate carcinogenesis, and has been correlated with greater disease severity. Both EGCG and omega-3 FA have been shown in vitro and in vivo to inhibit this overexpression of FAS. The primary objective or our proposal is to elucidate in men at high risk for prostate cancer, a potential biologic mechanism whereby EGCG, alone or in combination with omega-3 FA, may alter cellular composition and growth, thereby reducing overall risk of prostate cancer. In the proposed GCRC sponsored, randomized, placebo-controlled study we will evaluate the independent and joint effect of EGCG and EGCG plus omega-3 FA on FAS expression, FAS activity, cell proliferation and apoptosis in bengin, pre-neoplastic and neoplastic prostate tissue of men undergoing repeat prostate biopsy. Findings from this study will provide some of the first evidence linking the observed associations between factors modifiable by diet (primarily EGCG and omega-3 FA) and a specific biologic mechanism (FAS pathway) that is suggested to influence prostate carcinogenesis. The elucidation of a single oncogenic pathway that may be regulated by diet may provide a new and exciting opportunity for targeted prevention therapy.