Are anthocyanins necessary for oral cancer chemoprevention by berries?

浆果化学预防口腔癌是否需要花青素？

基本信息

批准号：
7590645
负责人：
CHRISTOPHER M WEGHORST
金额：
$ 7.5万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-12 至 2010-08-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7590645
关键词：
Address Animal Cancer Model Animal Model Animals Anthocyanins Anthracenes Antioxidants Apoptosis Berry Bioflavonoid Biological Biological Markers Breast Carcinogens Cell Proliferation Cheek structure Chemoprevention Chemopreventive Agent Colon Colon Carcinoma Color Complex Complex Mixtures Consumption Count Cultured Cells Daily Data Depth Development Diet Ellagi-Tannins Ellagic Acid Epidemiologic Studies Esophageal Flavonols Foundations Fruit Future Gallo-Tannins Gene Expression Genes Genomics Genus Cola Hamsters Harvest Human In Vitro Inflammation Intake Kaempferols Laboratories Lesion Lignans Literature Malignant Neoplasms Mammary gland Methods Modeling Molecular Molecular Target Mouth Neoplasms Nature Neoplasm Metastasis Oral Outcome Paint Pathway interactions Pattern Population Powder dose form Preparation Prevention Quercetin Raspberries Regulatory Pathway Research Design Risk Skin Cancer Strawberries Time Week anthracene base cancer cell cancer risk chemical carcinogen day defined contribution feeding fruits and vegetables kaempferol lot production malignant mouth neoplasm neoplastic cell novel nutrition oral tumorigenesis phenolic acid polyphenol pre-clinical preclinical study prevent tumor tumor progression tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Numerous epidemiological studies have shown a strong correlation between consumption of fresh fruits and vegetables and a decreased risk of oral cancer. Several preclinical studies demonstrate the remarkable chemopreventive activity of two berry fruits, black raspberries and strawberries, that inhibit human oral cancer cell proliferation in vitro and development of chemically-induced aerodigestive tract tumors in animals. A pressing, yet unanswered, question remains "What types of polyphenols in fruit are primarily responsible for these activities?" Prior studies have employed lyophilized powders or extracts of ripe fruits containing a complex mixture of berry polyphenols of which a major group is the anthocyanins. Epidemiological evidence suggests that diets rich in anthocyanins (colored fruits and vegetables) reduce the overall risk of cancer and laboratory evidence illustrates the inhibition of proliferation of tumor cells in culture and prevention of tumors in animal models. However, there are numerous other fruit phenolics in berries that have demonstrated antioxidant, antiproliferative, and chemopreventive activity in both cell cultures and animal models of cancer. Among these are the phenolic acids, (gallic, procatechuic, p-hydroxybenzoic, caffeic, p- coumaric, ferulic, chlorogenic, and ellagic acids), the flavonols (quercetin, kaempferol, mycetrin, and isorhamntin), and complex polyphenols (lignans, ellagitannin, and gallotannin). To examine the chemopreventive capacity of these latter berry phenolics, separate from their combined activity with anthocyanins, we propose to evaluate green berry fruits (with minimal anthocyanin content) and ripe berry fruits (with high levels of anthocyanins) for inhibition of oral tumorigenesis in an animal model and to determine their effect on modulation of cancer-associated genes. Hypothesis: We hypothesize that bioactive phenolics found in green strawberries and black raspberries, independent of the anthocyanins, will inhibit tumorigenesis just as effectively as ripe berries in an animal model of oral cancer and will modulate the expression of critical genes associated with oral cancer. Methods: Hamster pellets will be prepared using 5% and 10% green and ripe strawberries and black raspberries. Beginning 7 days after commencement of feeding with berry pellets, cheek pouches will be painted 3x/week for six weeks with the chemical carcinogen 7,12-dimethylbenz(a)anthracene. Berry pellets will be given during, and for six weeks after, carcinogen treatment. At 12-13 weeks, cheek pouches will be evaluated for total lesions and tumors and for modulation of caner- associated gene expression. Significance: The novel studies outlined herein will provide a practical assessment of the chemopreventive potential of berries that are essentially devoid of anthocyanins, as well as an opportunity to determine their ability to modulate specific molecular targets in oral cancers. The outcome will provide a suitable foundation for in-depth studies designed to elucidate the chemoprevention potential for oral cancer of various bioactive berry components.

描述（由申请人提供）：大量流行病学研究表明，食用新鲜水果和蔬菜与降低口腔癌风险之间存在很强的相关性。几项临床前研究表明，黑树莓和草莓这两种浆果具有显着的化学预防活性，可在体外抑制人口腔癌细胞增殖以及化学诱导的动物呼吸消化道肿瘤的发展。一个紧迫但尚未解答的问题仍然是“水果中哪些类型的多酚主要负责这些活动？”先前的研究使用了冻干粉末或成熟水果的提取物，其中含有复杂的浆果多酚混合物，其中主要成分是花青素。流行病学证据表明，富含花青素（有色水果和蔬菜）的饮食可降低患癌症的总体风险，实验室证据表明，可以抑制培养物中肿瘤细胞的增殖，并预防动物模型中的肿瘤。然而，浆果中还有许多其他水果酚类物质，在细胞培养物和癌症动物模型中都显示出抗氧化、抗增殖和化学预防活性。其中包括酚酸（没食子酸、原儿茶酸、对羟基苯甲酸、咖啡酸、对香豆酸、阿魏酸、绿原酸和鞣花酸）、黄酮醇（槲皮素、山奈酚、霉菌素和异鼠李素）和复合多酚（木脂素、鞣花单宁和没食子单宁）。为了检查这些浆果酚类物质的化学预防能力，与它们与花青素的组合活性分开，我们建议评估绿色浆果（花青素含量最低）和成熟浆果（花青素含量高）在口腔肿瘤发生中的抑制作用。动物模型并确定它们对癌症相关基因调节的影响。假设：我们假设在绿色草莓和黑树莓中发现的生物活性酚类物质（独立于花青素）将像口腔癌动物模型中的成熟浆果一样有效地抑制肿瘤发生，并调节与口腔癌相关的关键基因的表达。方法：使用 5% 和 10% 绿色和成熟的草莓以及黑树莓制备仓鼠颗粒。从开始饲喂浆果颗粒后 7 天开始，将在颊囊上每周 3 次涂上化学致癌物 7,12-二甲基苯并（a）蒽，持续六周。浆果颗粒将在致癌剂治疗期间和治疗后六周内给予。在 12-13 周时，将评估颊囊的总病变和肿瘤以及癌症相关基因表达的调节。意义：本文概述的新颖研究将为基本上不含花青素的浆果的化学预防潜力提供实际评估，并提供确定其调节口腔癌特定分子靶点的能力的机会。该结果将为旨在阐明各种生物活性浆果成分对口腔癌的化学预防潜力的深入研究提供合适的基础。