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剂已经得到了相当大的关注 由于在细胞培养物中的生长抑制作用， 在动物模型中的作用以及对降低癌症和心脏病风险的作用 前瞻性人类队列研究中的疾病。 绿色中的多酚含量 红茶中的茶黄素和茶红素被认为是 负责抗癌活性的药物。 的比较 由以下茶包制备的绿色和红茶的多酚含量 不同的生产厂家表明，由于茶叶含量不同， 在袋中，一些红茶制剂具有相似的儿茶素含量， 到绿色茶制品。 研究还表明，抗氧化剂 通过ORAC测定法测定的容量显示出 不同的茶制剂，红茶显示出最高的ORAC值。 只有有限数量的研究调查生物利用度 绿色和红茶的区别。 因此，我们建议研究 茶多酚及其对小鼠血清抗氧化能力的影响 绿色与红茶和绿色提取物膳食补充剂相比， 前列腺癌的患者在前列腺切除术之前。 将血清 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。 前列腺癌被选中 作为研究儿茶素化学预防作用的良好模型 因为前列腺癌生长缓慢， 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 疾病预防的重点是集中注意力。 儿茶素浓度 在体外研究中使用的药物浓度通常高于血浆浓度 在茶消费之后。 没有研究表明 人体内儿茶素的浓度。 因此，我们建议 前列腺组织中儿茶素和茶黄素的浓度 服用绿色茶、红茶或 绿色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， 雄激素反应，多胺生物合成中的速率控制酶。 将分析尿液中的多酚以检查依从性。 拟议 研究将证明，如果消费5杯绿色茶，红茶 或绿色茶提取物膳食补充剂足以增加 前列腺组织中的儿茶素浓度达到可以影响 促进癌发生的细胞过程。 茶、血清、纸巾和 将使用HPLC方法分析尿多酚浓度 在我们的实验室里开发的。 血清抗氧化能力将是 最近使用氧自由基吸收能力测定法测定 建立在我们的实验室。将测定ODC酶活性 测量从14 C鸟氨酸释放14 C CO2。 这些研究将 提供设计研究的重要信息，以批判性地检验 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.