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

• 批准号: 8515361
• 负责人: MARTHA A BELURY
• 金额: $ 7.11万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-18 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8515361
• 关键词: 5' -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

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.

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。我们最近报道了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。

项目成果

The flavonoid, naringenin, decreases adipose tissue mass and attenuates ovariectomy-associated metabolic disturbances in mice.

• DOI: 10.1186/1743-7075-12-1
• 发表时间: 2015
• 期刊: Nutrition & metabolism
• 影响因子: 4.5
• 作者: Ke JY;Kliewer KL;Hamad EM;Cole RM;Powell KA;Andridge RR;Straka SR;Yee LD;Belury MA
• 通讯作者: Belury MA