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

描述(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并在早期诊断这种疾病的能力。但是，在因PSA升高而接受前列腺活检的男性中，只有大约25%的人被诊断为前列腺癌。对于那些活检呈阴性的男性来说，他们对前列腺癌风险的认识已经大大提高，人们可能会强烈希望找到方法来降低他们最终患前列腺癌的风险。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omega-3脂肪酸(omega-3 FA)和绿茶儿茶素，已被假设可降低前列腺癌风险。然而，重要的是要了解它们可能如何发挥作用以减缓或抑制前列腺癌发生的生物学机制。一种特殊的生物途径，可以被omega-3 FA和特定的绿茶儿茶素，表没食子儿茶素没食子酸酯(EGCG)改变，是脂肪酸合成酶(FAS)途径。Fas是一种促脂多酶，催化从头合成脂肪酸的最后一步，已被证明在前列腺癌的发生中高表达，并与更严重的疾病相关。EGCG和omega-3 FA在体外和体内都被证明可以抑制这种Fas的过度表达。 我们的主要目标或建议是阐明前列腺癌高危男性的潜在生物学机制，即EGCG单独或与omega-3 FA联合使用可能改变细胞组成和生长，从而降低前列腺癌的总体风险。在这项由GCRC赞助、随机、安慰剂对照的拟议研究中，我们将评估EGCG和EGCG加omega-3 FA对接受重复前列腺活检的男性Bengin、肿瘤前病变和肿瘤组织中Fas表达、Fas活性、细胞增殖和凋亡的独立和联合影响。 这项研究的结果将提供一些初步证据，将饮食可改变的因子(主要是EGCG和omega-3 FA)与特定的生物机制(Fas途径)之间的联系联系起来，后者被认为影响前列腺癌的发生。阐明可能受饮食调控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.