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

EGCG 和 Omega-3 脂肪酸对前列腺脂肪酸合酶活性的影响

• 批准号: 7478587
• 负责人: JACKILEN SHANNON
• 金额: $ 21.98万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478587
• 关键词: ADD-1 protein; Address; Apoptosis; Apoptotic; Awareness; Biological Factors; Biopsy; Cell Death; Cell Proliferation; Clinical Research; Complementary and alternative medicine; Data; Diagnosis; Diet; Disease; Epigallocatechin Gallate; Fatty Acids; Fatty-acid synthase; Fish Oils; Gland; Green tea; Growth; Health Sciences; Histocompatibility Testing; In Vitro; Intervention; Intervention Studies; Investigation; Joints; Link; Malignant neoplasm of prostate; Mediating; Methods; National Center for Complementary and Alternative Medicine; Numbers; Omega-3 Fatty Acids; Oncogenic; Oregon; Pathway interactions; Placebos; Policies; Prevention therapy; Prostate; Prostate-Specific Antigen; Protein Overexpression; Purpose; Research; Research Personnel; Risk; Safety; Sampling; Screening procedure; Severity of illness; Staging; Supplementation; Testing; Text; Time; Tissues; Universities; Variant; cancer diagnosis; cancer risk; carcinogenesis; desire; gallocatechol; high risk men; improved; in vivo; innovation; men; neoplastic; neurophysiology; programs; randomized placebo controlled trial; response; tumor

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.

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有前列腺癌风险的男性并在早期阶段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% 被诊断患有前列腺癌。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大大提高，并且可能强烈希望找到方法来降低最终患上这种疾病的风险。其中许多男性可能会寻求补充和替代药物 (CAM)，以试图改变患前列腺癌的风险。许多 CAM 化合物，包括 omega-3 脂肪酸 (omega-3 FA) 和绿茶儿茶素，被认为可以降低前列腺癌风险。然而，了解它们如何减缓或抑制前列腺癌发生的生物学机制非常重要。一种特殊的生物途径是脂肪酸合酶 (FAS) 途径，该途径可能会被 omega -3 FA 和特定绿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，可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过程中高度表达，并且与更严重的疾病严重程度相关。 EGCG 和 omega-3 FA 均已在体外和体内被证明可以抑制 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一种潜在生物学机制，即 EGCG 单独或与 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。在拟议的 GCRC 赞助的随机安慰剂对照研究中，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前列腺组织中的 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，将观察到的饮食改变因素（主要是 EGCG 和 omega-3 FA）与影响前列腺癌发生的特定生物机制（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令人兴奋的新机会。