In vivo effects of sulforaphane supplementation on normal human prostate

补充萝卜硫素对正常人前列腺的体内影响

基本信息

批准号：
8069167
负责人：
BEATRICE S KNUDSEN
金额：
--
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-23 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8069167
关键词：
AKR1C1 Adopted Adverse effects Adverse event Affect Animals Antioxidants Basic Science Biological Assay Biopsy Brassica Brassica oleracea Brassicaceae Broccoli - dietary Catabolism Cell Proliferation Cells Cessation of life Clinical Trials Consumption Controlled Clinical Trials Cyclin A Cyclin B DNA Deoxyguanosine Detection Development Diagnosis Diagnostic Diet Double-Blind Method Drug Metabolic Detoxication Enzyme Induction Enzyme-Linked Immunosorbent Assay Enzymes Epidemiologic Studies Epithelium Experimental Animal Model F2-Isoprostanes Family Food GSTM1 gene Gene Expression Genes Genotype Goals Growth Health High Pressure Liquid Chromatography Human Immunohistochemistry In Vitro Intervention Isothiocyanates Knowledge Lipids Literature MAP Kinase Gene MAPK8 gene Malignant Neoplasms Malignant neoplasm of prostate Mass Spectrum Analysis Measurable Measures Metabolism Modeling Monitor NQO1 gene Oxidative Stress Pathway interactions Peroxidases Phase Placebo Control Placebos Plants Prevention Preventive Production Prostate Prostatectomy Prostatic Public Health Radical Prostatectomy Randomized Randomized Clinical Trials Recommendation Research Retinoblastoma Protein Reverse Transcriptase Polymerase Chain Reaction SRD5A2 gene Serum Signal Pathway Signal Transduction Pathway Stanolone Sulforaphane Supplementation Testing Time Tissues Toxic effect Translations United States Vegetables Work anticancer research base cancer cell cancer diagnosis cancer prevention cancer risk candidate validation cost cost effective design feeding glutathione S-transferase alpha in vitro Model in vivo male men novel oxidation oxidative damage oxidized lipid prostate cancer prevention randomized trial response steroid hormone metabolism thioredoxin reductase

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this proposal is to use a novel in vivo human intervention model to understand the activities of sulforaphane (the bioactive compound in Brassica vegetables) in human prostate since these bioactive plant compounds are believed to be associated with prostate cancer risk. Several large, well-designed epidemiological studies have found that regular consumption of vegetables in the Brassica oleracea (Cruciferae) family is associated with reduced prostate cancer risk. Further, there is ample evidence from in vitro and experimental animal studies, along with a limited number of human feeding studies, that metabolites of the these compounds induce phase II detoxification enzymes, decrease cancer growth, and modulate oxidative stress. However, the in vivo effects of the bioactive compounds in Brassica vegetables on human prostate are unknown. Here we propose a randomized, double-blinded, placebo-controlled clinical trial to evaluate the in vivo effects of a high-sulforaphane, broccoli sprout extract on human prostate tissue. We will randomize 100 men with localized, low-grade prostate cancer, and use prostate tissue collected at both the time of diagnosis (biopsy) and prostatectomy to assess carefully selected and evaluated measures of phase II detoxifying enzyme induction, intra-prostatic steroid hormone metabolism, oxidative damage, and growth of prostate cancer cells. The Primary Specific Aims are to test whether the broccoli sprout extract: (1) induces an antioxidant response and reduces oxidative damage in human prostate and (2) increases DHT catabolism and reduces intra-prostatic dihydrotestosterone (DHT) concentration. Secondary Aims will examine: (1) whether the high-sulforaphane broccoli sprout extract affects pathways associated with development and/or early progression of prostate cancer and (2) whether GSTM1 genotype modifies responses to the high- sulforaphane broccoli sprout extract. We hope to confirm in humans the findings from studies examining sulforaphane in animal and in vitro models, which would be an important advance in our work toward the dietary prevention of prostate cancer. We believe it is likely that sulforaphane could be an effective preventive agent for prostate cancer, and that research to evaluate the effects of Brassica compounds in humans is well motivated. PUBLIC HEALTH RELEVANCE: Project Narrative Prostate cancer is the most commonly diagnosed cancer among men as well as the second leading cause of male cancer deaths in the United States. Dietary change interventions, or use of bioactive compounds derived from food, are an especially appealing approach to prostate cancer prevention due to their low cost, low toxicity, and absence of adverse events. Before public health recommendations for prostate cancer can be offered to men, a better understanding of the potential mechanisms, as well as efficacy of the agents is needed. This randomized trial of bioactive compounds in broccoli may provide an important, cost-effective, low-adverse-event means of prevention of the most common cancer in US males.

描述（由申请人提供）：该提案的总体目标是使用一种新颖的体内人类干预模型来了解萝卜硫素（芸苔属蔬菜中的生物活性化合物）在人类前列腺中的活性，因为这些生物活性植物化合物被认为与前列腺癌风险相关。几项精心设计的大型流行病学研究发现，经常食用十字花科蔬菜与降低前列腺癌风险相关。此外，来自体外和实验动物研究以及有限数量的人类喂养研究的充足证据表明，这些化合物的代谢物可诱导 II 相解毒酶、减少癌症生长并调节氧化应激。然而，芸苔类蔬菜中的生物活性化合物对人类前列腺的体内影响尚不清楚。在这里，我们提出了一项随机、双盲、安慰剂对照临床试验，以评估高萝卜硫素、西兰花芽提取物对人类前列腺组织的体内影响。我们将随机抽取 100 名患有局部低级别前列腺癌的男性，并使用在诊断（活检）和前列腺切除术时收集的前列腺组织来评估精心挑选和评估的 II 期解毒酶诱导、前列腺内类固醇激素代谢的指标、氧化损伤和前列腺癌细胞的生长。主要具体目标是测试西兰花芽提取物是否：(1) 诱导抗氧化反应并减少人类前列腺的氧化损伤；(2) 增加 DHT 分解代谢并降低前列腺内二氢睾酮 (DHT) 浓度。次要目标将检查：(1) 高萝卜硫素西兰花芽提取物是否影响与前列腺癌的发生和/或早期进展相关的途径，以及 (2) GSTM1 基因型是否改变对高萝卜硫素西兰花芽提取物的反应。我们希望在人类身上证实在动物和体外模型中检查萝卜硫素的研究结果，这将是我们在前列腺癌饮食预防方面的工作的重要进展。我们相信萝卜硫素可能是前列腺癌的有效预防剂，并且评估芸苔属化合物对人类影响的研究也很积极。公共健康相关性：项目叙述前列腺癌是男性中最常诊断出的癌症，也是美国男性癌症死亡的第二大原因。饮食改变干预或使用从食物中提取的生物活性化合物是预防前列腺癌的一种特别有吸引力的方法，因为它们成本低、毒性低且无不良事件。在向男性提供前列腺癌的公共卫生建议之前，需要更好地了解潜在机制以及药物的功效。这项对西兰花中生物活性化合物的随机试验可能为预防美国男性最常见的癌症提供一种重要的、具有成本效益的、低不良事件的方法。