Bioavailability of Tea Polyphenols in Prostate Cancer

描述(由申请人提供)： 茶作为一种癌症化学预防药物受到了相当大的关注。 由于细胞培养中的生长抑制作用，抗癌 动物模型的作用及对降低癌症和心脏风险的作用 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认为是 负责抗癌活性的药物。两个版本之间的比较 绿茶和红茶中多酚含量的测定 不同的厂家表示，由于茶叶的含量不同 在袋装中，一些红茶制剂的儿茶素含量与之类似 到绿茶制剂。研究还表明，抗氧化剂 ORAC测定的容量显示出不同的 不同茶剂与红茶的ORAC值最高。 只有有限数量的研究对生物利用度进行了调查 绿茶和红茶。因此，我们建议对其生物利用度进行研究。 茶多酚及其对小鼠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 前列腺癌患者在前列腺癌切除前。血清将会是 也用于研究雄激素依赖的体外生长抑制作用 LNCaP和雄激素非依赖性PC-3细胞株。前列腺癌被选为 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，通常处于亚临床状态 一段较长的时间。因此，化学预防特别适合 作为维持前列腺癌休眠状态的主要或辅助治疗 州政府。关于膳食补充剂有效性的一个重要考虑 在疾病预防中是集中的问题。儿茶素浓度 在体外研究中使用的药物浓度往往高于血浆浓度 在喝茶后到达。没有研究表明组织 儿茶素在人体内的浓度。因此，我们提议测量 前列腺组织中儿茶素和茶黄素的浓度 在饮用绿茶、红茶或红茶5天后行前列腺切除术 绿茶提取物膳食补充剂。此外，前列腺组织将被 鸟氨酸脱羧酶(ODC)活性分析 多胺生物合成中雄激素反应的速率控制酶。 将对尿液进行多酚分析，以检查合规性。建议数 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 导致癌变的细胞过程。茶、血清、纸巾和 尿液多酚浓度将使用高效液相色谱法进行分析。 这是我们实验室研发的。血清的抗氧化能力将是 新近用氧自由基吸收能力测定法测定 在我们的实验室建立。将测定ODC酶的活性 测量14C鸟氨酸释放的14C二氧化碳。这些研究将 为设计研究提供重要信息，以严格测试其作用 饮食补充剂在前列腺癌中的应用。

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.