Breast Cancer Chemoprevention Potential of Common Spices

常见香料的乳腺癌化学预防潜力

• 批准号: 7319537
• 负责人: RAMESH C GUPTA
• 金额: $ 29.62万
• 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/7319537
• 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; 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; PCNA gene; Pathology; Phytochemical; Plants; Polymerase Chain Reaction; Rattus; Risk; Route; Silastic; Site; Spices; Standards of Weights and Measures; Subgroup; System; Testing; Time; Tissues; United States; Western Blotting; Woman; Work; base; carcinogenicity; disorder prevention; improved; in vivo; indexing; malignant breast neoplasm; 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氧化DNA损伤，这可能导致基因突变并最终导致乳腺癌。越来越清楚的是，乳腺癌死亡率问题不能仅通过治疗来解决。因此，人们的注意力理所当然地转向了早期暴露标记物的检测和疾病预防。与当前的趋势不同，该应用重点关注属于一种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。我们假设伞形科常见香料（茴香、香菜、香菜、孜然、莳萝和茴香）中存在的植物化学物质将有利地改变雌激素代谢、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，可显着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香料的作用模式来识别有效的香料，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相关联。具体来说，i) 确定香料在短期体内试验中有利地调节雌激素代谢、氧化 DNA 加合和细胞增殖的潜力； ii) 确定测试香料抑制雌激素介导的乳腺肿瘤发生的功效，并将早期标志物的调节与肿瘤指数相关联； iii) 确定两种选定香料的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识别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级，并测试活性亚级分和纯化成分的抗雌激素致癌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可检测病变发生之前识别出罹患乳腺癌风险较高的女性，并通过使用常见的家用香料进行干预来预防该疾病。