Bioavailability and activity of dietary naringenin as a chemopreventive agent

膳食柚皮素作为化学预防剂的生物利用度和活性

基本信息

批准号：
8401774
负责人：
MARTHA A BELURY
金额：
$ 7.56万
依托单位：
OHIO STATE 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：
2012-07-18 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8401774
关键词：
5&apos -AMP-activated protein kinase Bioavailable Biological Biological Availability Blood Body Weight decreased Cells Chemopreventive Agent Colon Carcinoma Complement Data Diabetes Mellitus Diet Dose Eating Epidemiologic Studies Event Female Flavonoids Food Future Glucose Glycolysis Goals Grapefruit Growth Hepatic Hepatocyte Insulin Knowledge Lipids MCF7 cell Macronutrients Nutrition Malignant Neoplasms Mammary Neoplasms Mammary Tumorigenesis Mammary gland Metabolism Metformin Mus Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Obesity Pharmaceutical Preparations Postmenopause Pre-Clinical Model Preventive Relative (related person)Reporting Risk Role Signal Transduction Source Surface Testing Tissues Tomatoes Weight Gain Woman Work cancer risk cell growth cellular targeting design flavanoid glucose output glucose production improved insulin sensitivity malignant breast neoplasm mortality naringenin neoplastic cell oxidation prevent research study response tumor growth tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Type 2 diabetes increases the risk for developing breast cancer in postmenopausal women. Epidemiological studies have recently revealed that the glucose-lowering drug, metformin, reduces breast cancer in women with diabetes. We recently reported that the flavanoid, naringenin acts like metformin to lower glucose production by hepatocytes. Naringenin is surfacing as a chemopreventive agent in several preclinical models for cancer. Since the bioavailability, tissue accumulation and biological activity of dietar naringenin in mammary gland have not been reported, we propose to quantify the accumulation of naringenin in mammary tissues and blood then determine the ability of dietary naringenin to modulate growth of mammary tumors in obese female mice. There are three aims of this study. In Aim 1, we will test the hypothesis that increasing doses of dietary naringenin result in a dose- responsive accumulation of naringenin in blood and tissues without detrimental effects on food intake and weight gain. In Aim 2, we will test the hypothesis that naringenin reduces the rate of growth of tumors. In Aim 3, we will test the hypothesis that dietary naringenin modulates signaling events involved with tumorigenesis and metabolism. Accomplishment of the experiments outlined in this proposal will determine whether there is rationale for future experiments to identify dietary naringenin as a preventive agent against breast cancer. PUBLIC HEALTH RELEVANCE: Type 2 diabetes increases the risk for developing breast cancer in postmenopausal women. Our goal is to find dietary approaches that complement weight loss to reduce the risk and mortality from breast cancer in postmenopausal women. Experiments outlined in this application seek to use a pre-clinical model for dysregulated metabolism to quantify the accumulation and chemopreventive activity of naringenin in mammary tumorigenesis.

描述（由申请人提供）：2 型糖尿病会增加绝经后妇女患乳腺癌的风险。流行病学研究最近表明，降糖药物二甲双胍可以降低糖尿病女性患乳腺癌的风险。我们最近报道，类黄酮柚皮素的作用类似于二甲双胍，可以降低肝细胞产生的葡萄糖。柚皮素在多种癌症临床前模型中作为化学预防剂出现。由于膳食柚皮素在乳腺中的生物利用度、组织积累和生物活性尚未报道，我们建议量化柚皮素在乳腺组织和血液中的积累，然后确定膳食柚皮素调节肥胖雌性小鼠乳腺肿瘤生长的能力。这项研究有三个目的。在目标 1 中，我们将检验以下假设：增加膳食柚皮素剂量会导致剂量- 柚皮素在血液和组织中反应性积累，而不会对食物摄入和体重增加产生不利影响。在目标 2 中，我们将检验柚皮素降低肿瘤生长速度的假设。在目标 3 中，我们将检验膳食柚皮素调节与肿瘤发生和代谢相关的信号事件的假设。该提案中概述的实验的完成将决定未来实验是否有理由确定膳食柚皮素作为乳腺癌的预防剂。公共卫生相关性：2 型糖尿病会增加绝经后妇女患乳腺癌的风险。我们的目标是找到补充减肥的饮食方法，以降低绝经后妇女患乳腺癌的风险和死亡率。本申请中概述的实验试图使用代谢失调的临床前模型来量化柚皮素在乳腺肿瘤发生中的积累和化学预防活性。