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）筛查已大大提高了我们识别患有前列腺癌风险并在早期诊断这种疾病的男性的能力。但是，在因PSA升高而进行前列腺活检的男性中，只有大约25％的人被诊断出患有前列腺癌。对于那些活检阴性的男性，人们对前列腺癌风险的认识已经大大增加，并且可能有强烈的渴望识别降低其最终患上这种疾病风险的方法。这些男人中的许多人可能会寻找互补和替代药物（CAM），以改变其前列腺癌的风险。假设许多CAM化合物，包括Omega-3脂肪酸（Omega-3 FA）和绿茶儿茶素以降低前列腺癌的风险。但是，重要的是要了解它们如何起作用以减慢或抑制前列腺癌发生的生物学机制。欧米茄-3 FA和特定的绿茶儿茶素epigallocatechin-3-gallate（EGCG）可能会改变一种特定的生物途径，是脂肪酸合酶（FAS）途径。 FAS是一种催化从头脂肪酸合成的最后一步的脂肪生物多酶，已显示出在前列腺癌中高度表达，并且与较大的疾病严重程度相关。 EGCG和Omega-3 FA都在体外和体内都显示出抑制FAS的过表达。 主要目标或我们的建议是阐明患有前列腺癌高风险的男性，这是一种潜在的生物学机制，因此，EGCG单独或与omega-3 FA结合使用，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，随机，安慰剂控制的研究中，我们将评估EGCG和EGCG加上Omega-3 FA对FAS表达，FAS活性，细胞增殖和凋亡的独立和关节作用，孟买，持续性和肿瘤前和肿瘤的前列腺组织的重复训练。 这项研究的发现将提供一些第一个证据，这些证据与观察到的因素之间的关联（主要是EGCG和Omega-3 FA）与建议影响前列腺癌发生的特定生物学机制（FAS途径）之间的关联。可能通过饮食调节的单个致癌途径的阐明可能为有针对性的预防疗法提供了一个新的令人兴奋的机会。