Prevention of Bladder Cancer with Broccoli Sprouts

用西兰花芽预防膀胱癌

• 批准号: 6858819
• 负责人: YUESHENG ZHANG
• 金额: $ 23.42万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6858819
• 关键词: Cruciferae; antineoplastics; apoptosis; biomarker; bladder neoplasm; cancer prevention; carcinogenesis; cell growth regulation; chemical carcinogen; chemoprevention; detoxification; enzyme activity; enzyme induction /repression; glucuronosyltransferase; glutathione transferase; human tissue; laboratory rat; nonhuman therapy evaluation; nutrition aspect of cancer; nutrition related tag; oral administration; plant extracts; sulfoxide; tissue /cell culture; urinary bladder epithelium; Cruciferae; antineoplastics; apoptosis; biomarker; bladder neoplasm; cancer prevention; carcinogenesis; cell growth regulation; chemical carcinogen; chemoprevention; detoxification; enzyme activity; enzyme induction /repression; glucuronosyltransferase; glutathione transferase; human tissue; laboratory rat; nonhuman therapy evaluation; nutrition aspect of cancer; nutrition related tag; oral administration; plant extracts; sulfoxide; tissue /cell culture; urinary bladder epithelium

DESCRIPTION (provided by applicant): This project focuses on the cancer preventive activity of broccoli sprout extracts in the bladder. The hypothesis to be tested is that broccoli sprout extracts are able to suppress tumorigenesis in the bladder by inducing carcinogen-detoxifying enzymes, inducing apoptosis, and inhibiting cell proliferation, all of which contribute, perhaps synergistically, to the prevention of carcinogenesis. Molecular markers relevant to these biological events, as well as inhibition of tumorigenesis will be studied. Broccoli sprouts are the richest plant source of sulforaphane, which is known to possess the above-described chemopreventive mechanisms. Both sulforaphane and broccoli sprout extracts have been shown to inhibit tumorigenesis in animal models (non-bladder tissues). Particularly, ingested sulforaphane in humans is disposed rapidly and concentrated in urine, making bladder epithelial cells probably the most exposed cells to sulforaphane in the body. The overwhelming majority of bladder cancers originate from the epithelial cells. Aim 1 is to determine the effect of broccoli sprout extracts on the expression of critical Phase 2 detoxification enzymes in cultured human bladder epithelial cells. Glutathione transferase and UDP-glucuronosyl-transferase, whose deficiencies have been linked to bladder carcinogenesis, will be examined using both enzyme activity analysis and Western blot analysis. Aim 2 is to determine the effect of broccoli sprout extracts on apoptosis and cell cycle regulation in cultured human bladder epithelial cells. The biomarkers include nuclear DNA fragmentation, activation of selected caspases, cell cycle change and related cell cycle regulators, using both flow cytometry and Western blot analysis. Aim 3 is to determine the in vivo cancer chemopreventive activity of broccoli sprout extracts in the rat bladder. Aim 3a is designed to determine the effect of orally administered broccoli sprout extracts on Phase 2 enzymes, apoptosis, and cell proliferation in bladder epithelia. Biomarkers, including the two Phase 2 enzymes listed above, plus the TUNEL and PCNA assays, will be evaluated immunohistochemically. Aim 3b is to determine the effect of orally administered broccoli sprout extracts on N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumorigenesis. Tumor incidence, tumor multiplicity, and the nature of each tumor will be determined.

描述（由申请人提供）：该项目着重于膀胱中西兰花发芽提取物的癌症预防活性。要检验的假设是，西兰花发芽提取物能够通过诱导致癌氧化酶，诱导细胞凋亡和抑制细胞增殖来抑制膀胱中的肿瘤发生，从而抑制细胞增殖，所有这些酶，也许会导致促成预防性的致癌作用。将研究与这些生物学事件有关的分子标记物以及抑制肿瘤发生。西兰花新芽是磺胺硫烷的最丰富植物来源，已知具有上述化学预防机制。硫烷和西兰花发芽提取物均已证明可以抑制动物模型（非叶片组织）中的肿瘤发生。特别是，人类摄入的磺胺素迅速处置并浓缩在尿液中，使膀胱上皮细胞可能是体内硫磷酸硫烷最暴露的细胞。绝大多数膀胱癌源自上皮细胞。目的1是确定西兰花发芽提取物对培养的人膀胱上皮细胞中临界2期解毒酶表达的影响。谷胱甘肽转移酶和UDP-葡萄糖基转移酶的缺陷将与膀胱癌变有关，将使用酶活性分析和蛋白质印迹分析进行检查。目的2是确定西兰花发芽提取物对培养的人膀胱上皮细胞中细胞凋亡和细胞周期调节的影响。生物标志物包括核DNA碎片，所选胱天蛋白酶的激活，细胞周期变化和相关的细胞周期调节剂，都使用流式细胞仪和蛋白质印迹分析。目标3是确定大鼠膀胱中西兰花发芽提取物的体内癌症化学预防活性。 AIM 3A旨在确定口服的西兰花发芽提取物对膀胱上皮中2阶段酶，凋亡和细胞增殖的影响。生物标志物，包括上面列出的两种2期2酶，以及TUNEL和PCNA分析，将通过免疫组织化学评估。 AIM 3B是确定口服的西兰花发芽提取物对N-丁基N-（4-羟基丁基）硝基胺诱导的膀胱肿瘤发生的影响。将确定肿瘤的发病率，肿瘤多样性和每个肿瘤的性质。