Bioavailability of Tea Polyphenols in Prostate Cancer

茶多酚在前列腺癌中的生物利用度

• 批准号: 6334562
• 负责人: Susanne Margarete Henning
• 金额: $ 7.65万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-15 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6334562
• 关键词: antineoplastics; clinical research; dietary supplements; enzyme activity; enzyme inhibitors; flavonoids; free radical oxygen; free radical scavengers; high performance liquid chromatography; human subject; male; neoplasm /cancer pharmacology; nutrition aspect of cancer; nutrition related tag; ornithine decarboxylase; oxidative stress; pharmacokinetics; plant extracts; prostate neoplasms; tea

DESCRIPTION (provided by applicant): Tea has gained considerable attention as a cancer chemopreventive agent because of the growth inhibitory effect in cell cultures, anticarcinogenic effects in animal models and effect on risk reduction of cancer and heart disease in prospective human cohort studies. The polyphenol content in green tea and theaflavins and thearubigins in black tea have been suggested as responsible agents for the anticarcinogenic activity. A comparison of the polyphenol content of green and black tea prepared from tea bags from different manufacturers showed that due to the different content of tea leaves in the bag, some black tea preparations have similar catechin content compared to green tea preparations. It also has been shown that the antioxidant capacity as determined by the ORAC assay shows great variations among different tea preparations with black tea showing the highest ORAC value. There are only a limited number of studies investigating the bioavailability of green and black tea. Therefore we propose to study the bioavailability of tea polyphenols and their effect on the serum antioxidative capacity from green tea compared to black tea and a green tea extract dietary supplement in men with prostate cancer before the time of prostatectomy. The serum will be also used to study the in vitro growth inhibiting effect in androgen-dependent LNCaP and androgen-independent PC-3 cell lines. Prostate cancer was selected as an excellent model to study the chemoprevention effect of tea catechins because prostate carcinoma are slow growing and often remain subclinical for an extended period of time. Therefore chemoprevention is particularly suited as a primary or adjuvant therapy for maintaining prostate cancer in a dormant state. An important consideration of the effectiveness of dietary supplements in disease prevention is the concentration issue. Catechin concentrations used in in vitro studies are frequently higher than plasma concentrations reached after tea consumption. There are no studies showing tissue concentrations of catechins in humans. Therefore we are proposing to measure prostate tissue concentration of catechins and theaflavins at the time of prostatectomy after 5 days of consumption of either green tea, black tea or a green tea extract dietary supplement. In addition prostate tissues will be analyzed for the enzyme activity of ornithine decarboxylase (ODC), an androgen-responsive, rate-controlling enzyme in the polyamine biosynthesis. Urine will be analyzed for polyphenols to check compliance. The proposed studies will demonstrate if the consumption of 5 cups of green tea, black tea or green tea extract dietary supplement is sufficient to increase the concentration of catechin in prostate tissue to a level which can affect cellular processes contributing to carcinogenesis. Tea, serum, tissue and urine polyphenol concentrations will be analyzed using an HPLC method developed in our laboratory. The serum antioxidant capacity will be determined using the oxygen radical absorbance capacity assay recently established in our laboratory. ODC enzyme activity will be determined measuring the release of 14C CO2 from 14C ornithine. These studies will provide information important in designing studies to critically test the role of dietary supplementation in prostate cancer.

描述（由申请人提供）： 作为一种癌症化学预防剂，茶引起了极大的关注 由于细胞培养物的生长抑制作用，抗癌作用 动物模型的影响以及对癌症和心脏降低风险的影响 前瞻性人类队列研究中的疾病。 绿色的多酚含量 建议在红茶中茶和theaflavins和thearubigins 负责抗癌活性的负责药。 比较 由绿茶和红茶的多酚含量用茶袋制备 不同的制造商表明，由于茶叶的含量不同 在袋子中，一些红茶制剂比较有类似的儿茶素含量 进行绿茶制备。 还显示抗氧化剂 由ORAC测定确定的能力显示出很大的差异 带有红茶的不同茶制剂显示出最高的ORAC价值。 研究生物利用度只有有限的研究 绿茶和红茶。 因此，我们建议研究 茶多酚及其对血清抗氧化能力的影响 绿茶与红茶和绿茶提取物相比 前列腺切除术之前的前列腺癌男性。 血清会 还用于研究依赖雄激素的体外生长抑制作用 LNCAP和雄激素无关的PC-3细胞系。 选择了前列腺癌 作为研究Catechins化学预防效应的出色模型 因为前列腺癌的生长缓慢，并且通常是亚临床的 长时间。 因此，化学预防特别适合 作为在休眠中维持前列腺癌的主要或辅助治疗 状态。 对饮食补充剂有效性的重要考虑 在疾病预防中是集中问题。 儿茶素浓度 用于体外研究通常高于血浆浓度 消耗茶后到达。 没有显示组织的研究 人类儿茶素的浓度。 因此，我们建议衡量 前列腺组织浓度在儿茶素和剧场时在 在食用绿茶，红茶或a饮食5天后，前列腺切除术 绿茶提取物饮食补充剂。 另外，前列腺组织将是 分析了鸟氨酸脱羧酶（ODC）的酶活性， 多胺生物合成中的雄激素反应性，速率控制酶。 尿液将分析多酚检查合规性。 提议 研究将证明是否消耗5杯绿茶，红茶 或绿茶提取物饮食补充剂足以增加 前列腺组织中儿茶素的浓度达到可能影响的水平 导致致癌作用的细胞过程。 茶，血清，组织和 尿液多酚浓度将使用HPLC方法分析 在我们的实验室中开发。 血清抗氧化能力将是 使用氧自由基吸光度能力测定法确定 在我们的实验室中建立。将确定ODC酶活性 测量从14C鸟嘌呤中释放14C CO2。 这些研究会 提供有关设计研究重要的信息，以批判性测试角色 饮食中补充前列腺癌。