Breast Cancer Chemoprevention Potential of Common Spices

常见香料的乳腺癌化学预防潜力

• 批准号: 7851052
• 负责人: RAMESH C GUPTA
• 金额: $ 28.12万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7851052
• 关键词: 17p; American Cancer Society; Anise Seed; Antioxidants; Apiaceae; Attention; Binding; Biological Assay; Biological Markers; Breast Cancer Model; Breast Cancer Prevention; Caraway; Cell Proliferation; Chemoprevention; Chemopreventive Agent; Coriander (Spice); Cumin (spice); Cytochrome P450; DNA Adduction; DNA Adducts; DNA Damage; Data; Development; Dill; Disease; Dose; Early Diagnosis; Enzymes; Epidemiology; Estradiol; Estrogen Metabolism; Estrogen Receptors; Estrogen Replacement Therapy; Estrogens; Family; Female; Fennel - dietary; Free Radicals; Future; Gene Mutation; Goals; Hormones; Housing; Human; Immunohistochemistry; Implant; In Vitro; Inbred ACI Rats; Intervention; Laboratories; Lead; Lesion; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Mammary Tumorigenesis; Measures; Mediating; Modeling; Molecular; Nutritionist; Oxidation-Reduction; Pathology; Phytochemical; Plants; Rattus; Risk; Route; Silastic; Site; Spices; Subgroup; System; Testing; Time; Tissues; United States; Western Blotting; Woman; Work; base; cancer chemoprevention; carcinogenicity; disorder prevention; efficacy testing; high risk; improved; in vivo; indexing; malignant breast neoplasm; meetings; mortality; multidisciplinary; oxidative DNA damage; prevent; subcutaneous; trend; tumor

DESCRIPTION (provided by applicant): The female hormone, 1715-estradiol (E2) and its metabolites, particularly, 4-hydroxy-E2 (4E2), have been implicated in breast cancer. It is proposed that excessive estrogen exposure causes cell proliferation, and oxidative DNA damage, which may lead to gene mutations and ultimately breast cancer. It has become increasingly clear that the problem of breast cancer mortality cannot be solved by treatment alone. Therefore, attention has rightfully turned to the detection of early markers of exposure and disease prevention. Unlike the current trend, this application focuses on common spices belonging to one plant family for their potential against estrogen-mediated breast cancer. We hypothesize that phytochemicals present in common spices belonging to the Apiaceae family (anise, caraway, coriander, cumin, dill, and fennel) will favorably alter estrogen metabolism, oxidative DNA damage and cell proliferation, and ultimately diminish the mammary tumorigenesis. Results obtained from extracts of all the six spices have shown drastic reduction of estrogen-mediated oxidative DNA damage by inhibiting P450 activity and/or scavenging hydroxy radicals, as well as antiproliferative activity in vivo, supporting our working hypothesis. Our major objectives are to identify efficacious spices based on their modes of action to inhibit estrogen-mediated mammary tumorigenesis, and to correlate early markers with tumor indices. Specifically, i) determine potential of the spices in short-term in vivo assays to favorably modulate estrogen metabolism, oxidative DNA adduction, and cell proliferation; ii) determine efficacy of test spices to inhibit estrogen-mediated mammary tumorigenesis, and correlate modulation of early markers with tumor indices; and iii) determine potential of extracts of two selected spices against estrogen-mediated mammary cancer. Data resulting from this project will identify spices with the potential to inhibit breast cancer, and establish an association of early biomarkers with tumor indices. Efficacious extracts will in future be fractionated and active subfractions and purified component(s) will be tested for their efficacy against estrogen carcinogenicity and their effects on early biomarkers. Thus, the early biomarkers may identify women who may be at the higher risk of developing breast cancer much before the onset of pathologically detectable lesions, and prevent the disease by intervention with common house-hold spices.

描述（由申请人提供）：女性激素1715-雌二醇（E2）及其代谢物，特别是4-羟基E2 (4E2)，与乳腺癌有关。有人提出，过量的雌激素暴露会导致细胞增殖和DNA氧化损伤，从而可能导致基因突变，最终导致乳腺癌。越来越清楚的是，乳腺癌死亡率问题不能单靠治疗来解决。因此，人们的注意力理所当然地转向了检测暴露的早期标志物和预防疾病。与目前的趋势不同，该应用侧重于属于一个植物家族的常见香料，因为它们具有对抗雌激素介导的乳腺癌的潜力。我们推测，属于Apiaceae家族的常见香料（八角、香菜、香菜、孜然、莳萝和茴香）中的植物化学物质有利于改变雌激素代谢、氧化DNA损伤和细胞增殖，并最终减少乳腺肿瘤的发生。从所有六种香料的提取物中获得的结果表明，通过抑制P450活性和/或清除羟基自由基，以及体内抗增殖活性，显著减少雌激素介导的氧化DNA损伤，支持我们的工作假设。我们的主要目标是根据它们的作用模式来确定有效的香料，以抑制雌激素介导的乳腺肿瘤发生，并将早期标志物与肿瘤指数联系起来。具体来说，i)确定香料在短期体内试验中的潜力，有利于调节雌激素代谢，氧化DNA内聚和细胞增殖；Ii)确定试验香料抑制雌激素介导的乳腺肿瘤发生的功效，并将早期标志物与肿瘤指数的调节联系起来；以及iii)确定两种选定香料提取物对抗雌激素介导的乳腺癌的潜力。该项目产生的数据将确定具有抑制乳腺癌潜力的香料，并建立早期生物标志物与肿瘤指数的关联。未来将对有效提取物进行分离，并对活性亚组分和纯化组分进行测试，以确定其对雌激素致癌性的有效性及其对早期生物标志物的影响。因此，早期生物标志物可以在病理学上可检测到的病变发生之前识别出患乳腺癌风险较高的妇女，并通过使用常见的家用香料进行干预来预防疾病。