Effect of Rhamnetin on Oxidative Stress and Prostate Cancer

鼠李素对氧化应激和前列腺癌的影响

基本信息

批准号：
8539586
负责人：
Sanjeev Shukla
金额：
$ 7.38万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-03 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8539586
关键词：
Adenocarcinoma Adverse effects Age Aging Aging-Related Process American Association of Cancer Research Antioxidants Apoptosis Atherosclerosis Biological Assay Blood Blood Circulation Cancer Patient Cell Culture Techniques Cell Nucleus Cells Chemopreventive Agent Clove Cytoplasm Cytosol Data Data Sources Development Diet Disease Disease-Free Survival Down-Regulation Drug Metabolic Detoxication Epithelial Cells Event Exhibits Fibroblast Growth Factor Receptors Flavanol Flavonoids Food Foxes Generations Genes Goals Growth Human IRS1 gene Immunoprecipitation Impaired cognition In Vitro Individual Infertility Insulin Insulin-Like Growth Factor I Integral Membrane Protein Lateral Lead MAP Kinase Gene MAPK14 gene Maintenance Malignant Epithelial Cell Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of prostate Masks Modeling Molecular Chaperones Molecular Target Mus Normal Cell Nuclear Oral Osteoporosis Oxidative Stress Paraquat Pathogenesis Phosphorylation Phosphotransferases Plant Preparations Plants Plasma Play Population Predisposition Premature aging syndrome Prevention strategy Prostate Prostate carcinoma Prostatic Diseases Proteins Public Health Reactive Oxygen Species Regulation Reporting Resistance Risk Factors Role Serum Signal Pathway Signal Transduction Stream Stress Testing Tissues Transgenic Mice Transgenic Organisms Tumor Suppression Tumor Suppressor Genes United States Work age effect age related base cancer cell cancer initiation cell growth clinically relevant dietary supplements feeding forkhead protein high risk human FRAP1 protein human disease in vivo klotho protein male meetings mouse model neoplastic cell normal aging novel oncoprotein p21 p66(ShcA) protein prevent prostate cancer cell prostate cancer prevention protective effect protein expression red wine response transcription factor

项目摘要

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.

描述（由申请人提供）：本研究的主要目标是确定天然植物黄酮酚的潜力，以维持对氧化菌株的耐药性以及通过Klotho（KL）（KL）和流浪汉中的Fox'O'信号的预防。衰老是前列腺癌的主要危险因素，已经提出，衰老和前列腺癌的机制彼此之间密切相关。随着年龄的增长，细胞和生物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以及细胞核的FoxO3a丧失有关。因此，迫切需要有效的药物，这可以减少细胞水平的氧化应激。 Rhamnetin是一种有前途的药物，在ORAC（氧自由基吸收能力）量表中排名很高，可能是减少氧化应激和赋予癌症化学预防效应的重要新范式。拟议的研究将探索鼠李糖蛋白在降低细胞水平下氧化应激方面的潜力，并补偿细胞培养研究中KL和FOXO3A的损失。此外，体内研究将确定鼠李糖蛋白是否有潜力调节非转基因的KL和FOXO3A水平，在随着年龄的增长的增长，保持对氧化应激的耐药性，这可能导致抑制前列腺癌和疾病自由存活。我们的长期目标是制定一种新颖有效的预防性预防策略，以了解前列腺癌发展的年龄增长的氧化应激产生的基本机制。公共卫生的意义：立即需要有效且与临床相关的策略来抑制前列腺癌的增长，主要是在高风险个体中，而没有任何副作用。特此使用丁香和其他草药制剂中的新药物，将测试鼠李糖蛋白，以防止前列腺癌和延长无疾病的生存。由于前列腺癌是一种男性衰老的疾病，在美国肺癌后仅次于肺癌，因此迫切需要预防策略。