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

• 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
• 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

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。几项大型的、精心设计的流行病学研究发现，经常食用甘蓝（十字花科）家族的蔬菜与降低前列腺癌风险有关。此外，从体外和实验动物研究以及沿着有限数量的人类喂养研究中有充分的证据表明，这些化合物的代谢物诱导II期解毒酶，减少癌症生长，并调节氧化应激。然而，芸苔属蔬菜中的生物活性化合物对人前列腺的体内作用尚不清楚。在这里，我们提出了一个随机，双盲，安慰剂对照的临床试验，以评估在体内的影响，高萝卜硫素，西兰花芽提取物对人类前列腺组织。我们将随机选择100名患有局限性低度前列腺癌的男性，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仔细选择和评估的II期解毒酶诱导，前列腺内类固醇激素代谢，氧化损伤和前列腺癌细胞生长的措施。主要特定目的是测试西兰花芽提取物是否：（1）诱导抗氧化反应并减少人前列腺中的氧化损伤，以及（2）增加DHT催化剂并降低前列腺内二氢睾酮（DHT）浓度。次要目标将审查：（1）高萝卜硫素西兰花芽提取物是否影响与前列腺癌的发展和/或早期进展相关的途径，和（2）GSTM 1基因型是否改变对高萝卜硫素西兰花芽提取物的应答。我们希望在人类中证实在动物和体外模型中检查萝卜硫素的研究结果，这将是我们在饮食预防前列腺癌方面的重要进展。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在人类中的作用的研究很有动机。公共卫生相关性：前列腺癌是男性中最常见的癌症，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来自食物的生物活性化合物是一种特别有吸引力的前列腺癌预防方法，因为它们成本低，毒性低，没有不良事件。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的机制以及药物的疗效。这项关于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。