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）： 茶作为癌症化学预防剂而受到广泛关注 由于细胞培养物中的生长抑制作用，具有抗癌作用 对动物模型的影响以及对降低癌症和心脏病风险的影响 前瞻性人类队列研究中的疾病。 绿色中的多酚含量 茶和红茶中的茶黄素和茶红素被建议为 抗癌活性的负责剂。 比较 茶袋制备的绿茶和红茶的多酚含量 不同厂家表明，由于茶叶含量不同 在袋子里，一些红茶制剂具有相似的儿茶素含量 绿茶制剂。 还表明，抗氧化剂 由 ORAC 测定确定的容量显示出很大的差异 不同的茶制剂中，红茶显示出最高的 ORAC 值。 调查生物利用度的研究数量有限 绿茶和红茶。 因此我们建议研究其生物利用度 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膳食补充剂的比较 在前列腺切除术之前患有前列腺癌的男性。 血清将是 也用于研究雄激素依赖性的体外生长抑制作用 LNCaP 和雄激素非依赖性 PC-3 细胞系。 被选为前列腺癌 作为研究茶儿茶素化学预防作用的优秀模型 因为前列腺癌生长缓慢，并且常常处于亚临床状态 很长一段时间。 因此化学预防特别适合 作为维持前列腺癌处于休眠状态的主要或辅助疗法 状态。 膳食补充剂有效性的重要考虑因素 防病就是浓度问题。 儿茶素浓度 体外研究中使用的浓度通常高于血浆浓度 喝茶后达到。 没有研究表明组织 儿茶素在人体中的浓度。 因此我们建议衡量 前列腺组织中儿茶素和茶黄素的浓度 饮用绿茶、红茶或茶 5 天后进行前列腺切除术 绿茶提取物膳食补充剂。 此外，前列腺组织将 分析鸟氨酸脱羧酶 (ODC) 的酶活性， 多胺生物合成中的雄激素响应性速率控制酶。 将分析尿液中的多酚以检查依从性。 拟议的 研究将证明如果饮用 5 杯绿茶、红茶 或绿茶提取物膳食补充剂足以增加 前列腺组织中儿茶素的浓度达到可以影响的水平 导致癌变的细胞过程。 茶、血清、组织和 将使用 HPLC 方法分析尿液多酚浓度 我们实验室开发的。 血清抗氧化能力为 最近使用氧自由基吸收能力测定法测定 在我们的实验室建立。 ODC酶活性将被测定 测量 14C 鸟氨酸释放 14C CO2。 这些研究将 提供设计研究以批判性测试角色的重要信息 前列腺癌的膳食补充剂。