Saw Palmetto, Cyclooxygenase, and Prostate Cancer

锯棕榈、环氧合酶和前列腺癌

• 批准号: 7264471
• 负责人: CHARLES E. ROSELLI
• 金额: $ 0.52万
• 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: 2006-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7264471
• 关键词: Saw; Palmetto; Cyclooxygenase; Prostate; Cancer

DESCRIPTION (provided by applicant): Phytotherapeutic formulations based on Saw Palmetto (Serenoa repens) are a traditional alternative therapy for the relief of lower urinary tract symptoms due to prostatic disease. The lipo-sterolic extract of saw palmetto (SPE) has been shown to be as effective as finasteride in the treatment of urinary symptoms from benign prostatic hyperplasia. SPE is one of the most commonly self-prescribed nutriceuticals used by patients with existing CaP in conjunction with conventional medical treatments however no data are available regarding its use for the treatment of prostate cancer (CaP) in men. It is generally agreed that cyclooxygenase-2 (COX-2) overexpression is associated with CaP and that selective inhibition of COX-2 may be useful for prevention and/or therapy of CaP. In vitro studies from our lab show that SPE inhibits the growth of human LnCaP cells, in part by inhibiting the expression of cyclooygenase-2 (COX-2) protein. Basal levels of COX-2 enzyme activity and protein expression are elevated in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, an animal model that exhibits molecular pathways of multistage prostate tumorigenesis. Treatment of TRAMP mice with a selective COX-2 inhibitor reduces CaP progression and metastases suggesting that COX-2 has a causative role for CaP development in this model. In contrast to recent reports of cardiotoxicity associated with selective COX-2 inhibitor drugs, SPE is well tolerated and has no significant toxicity. Thus, we propose to test the hypothesis that SPE can exert chemopreventative activity against CaP development and progression in TRAMP mice by inhibiting COX-2 activity and the production of prostaglandin E2. In addition, we will assess the effects of SPE on molecular targets in CaP linked to proliferation, inflammation, angiogenesis and invasiveness. The data from this study will contribute valuable information on whether SPE is an effective COX-2 inhibitor and test the popular notion that it has chemopreventative properties.

描述（由申请人提供）：基于锯棕榈（Serenoa Repens）的植物治疗配方是一种传统的替代疗法，可缓解由于前列腺疾病而减轻较低的尿路症状。 SAW Palmetto（SPE）的脂质脂提取物已被证明在治疗良性前列腺增生的泌尿症状方面与非那雄胺一样有效。 SPE是现有CAP患者与常规医疗治疗结合使用的最常见的自我规定的营养物之一，但是没有数据可用于治疗男性前列腺癌（CAP）。人们普遍认为，环氧合酶-2（COX-2）过表达与CAP相关，并且选择性抑制COX-2可能有助于预防和/或CAP治疗。我们实验室的体外研究表明，SPE抑制了人LNCAP细胞的生长，部分原因是抑制环氧酶-2（COX-2）蛋白的表达。在小鼠前列腺（Tramp）小鼠的转基因腺癌​​中，COX-2酶活性和蛋白质表达的基础水平升高，这是一种表现出多阶段前列腺肿瘤发生的分子途径的动物模型。用选择性COX-2抑制剂对流浪汉小鼠的处理可降低帽的进展和转移，这表明COX-2在该模型中对CAP发育具有致病作用。与选择性COX-2抑制剂药物相关的最新性心脏毒性的报道相反，SPE耐受性良好，没有明显的毒性。因此，我们建议检验以下假设：SPE可以通过抑制COX-2活性和前列腺素E2的产生来对流浪汉小鼠的CAP发育和进展发挥化学预防活性。此外，我们将评估SPE对与增殖，炎症，血管生成和侵袭性有关的CAP中分子靶标的影响。这项研究的数据将贡献有关SPE是否是有效的COX-2抑制剂的宝贵信息，并测试其具有化学预防特性的流行概念。