Effect of Rhamnetin on Oxidative Stress and Prostate Cancer

描述（由申请人提供）：本研究的主要目标是确定天然植物黄烷醇鼠李素在TRAMP小鼠中通过klotho（KL）和Fox“O”信号传导维持抗氧化应激和预防前列腺癌的潜力。衰老是前列腺癌的主要危险因素，并且已经提出衰老和前列腺癌的机制彼此密切相关。随着年龄的增长，在细胞和生物体水平上的氧化应激增加，这与分泌的KL蛋白的血清水平降低和FOXO 3a从细胞核的损失相关。因此，迫切需要一种有效的药剂，其可以在细胞水平上降低氧化应激。鼠李素是一种很有前途的药物，在ORAC（氧自由基吸收能力）量表中排名很高，可能是降低氧化应激和赋予癌症化学预防作用的重要新范例。拟议的研究将探索鼠李素在细胞水平上降低氧化应激的潜力，并补偿细胞培养研究中KL和FOXO 3a的损失。此外，体内研究将确定鼠李素是否具有随着年龄增加调节非转基因以及TRAMP模型中KL和Foxo3a水平的潜力，维持对氧化应激的抗性，这可能导致前列腺癌的抑制和无病生存。我们的长期目标是开发一种新的和有效的预防前列腺癌的策略，并了解随着年龄的增长，在前列腺癌的发展调节氧化应激产生的基本机制。公共卫生意义：迫切需要有效的和临床相关的策略来抑制前列腺癌生长，主要是在高风险个体中，而没有任何副作用。因此，使用一种新的代理商从甘草和其他草药制剂，鼠李素将被测试，以防止前列腺癌和延长无病生存。由于前列腺癌是一种老年男性人群的疾病，也是美国仅次于肺癌的第二大杀手，因此迫切需要预防策略。

DESCRIPTION (provided by applicant): The major goal of this study is to determine the potential of rhamnetin, a natural plant flavanol, in maintaining resistance against oxidative stres and prevention of prostate cancer through klotho (KL) and Fox 'O' signaling in TRAMP mice. Aging is a major risk factor for prostate cancer and it has been proposed that the mechanisms of aging and prostate cancer are intimately related with each other. With increasing age, there is an increase in oxidative stress at cellular and organismal level, which correlates with reduced serum levels of secreted KL protein and loss of FOXO3a from the nucleus. Hence, there is an urgent need for an effective agent, which can reduce oxidative stress at cellular level. Rhamnetin, is a promising agent, ranks high in ORAC (Oxygen Radical Absorbance Capacity) scale may be an important new paradigm for reducing oxidative stress and impart cancer chemopreventive effects. The proposed study will explore the potential of rhamnetin in reducing oxidative stress at cellular level and compensate the loss of KL and FOXO3a in cell culture studies. Furthermore, in vivo studies will determine whether rhamnetin has potential to regulate KL and Foxo3a levels in the non-transgenic as well as in TRAMP model with increasing age, maintaining resistance against oxidative stress which could lead to inhibition of prostate cancer and disease free survival. Our long term goal is to develop a novel and effective preventive strategy for prostate cancer and to understand the basic mechanism of oxidative stress generation with increasing age in the regulation of prostate cancer development. Public Health Significance: There is an immediate need for the effective and clinically relevant strategies for inhibition of prostate cancer growth, mainly in high-risk individuals, without any side effects. Hereby using a novel agent from the clove and other herbal preparation, rhamnetin will be tested to prevent prostate cancer and prolong disease free survival. Since prostate cancer is a disease of aging male population and second largest killer after lung cancer in the United States, prevention strategies are urgently needed.