NATURAL INHIBITORS OF CARCINOGENESIS

天然致癌抑制剂

• 批准号: 3094298
• 负责人: John M. Pezzuto
• 金额: $ 78.84万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-15 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3094298
• 关键词: antineoplastics; carcinogenesis inhibitor; chemoprevention; drug design /synthesis /production; drug screening /evaluation; medicinal plants; neoplasm /cancer pharmacology; plant extracts

It is well known that human cancer can result from exposure to a variety of natural and synthetic chemical carcinogens, many of which are ubiquitous environmental contaminants. Conversely, a number of substances have been established as inhibitors of chemically-induced tumorigenesis (e.g., antioxidants, indoles, aromatics isothiocyanates, coumarins, flavones, diterpenes, and vitamins). Most of these substances are naturally occurring and found in the diet of humans. However, since a systematic effort of exploring natural products as sources of chemopreventive agents has never been implemented, it is reasoned that many agents of interest remain to be uncovered. Thus, we currently proposed a program project comprised of six multidisciplinary, integrated research programs. The major aim of this program project is the identification, isolation and characterization (structural and mechanistic) of unique cancer chemopreventive agents from natural sources. For the accomplishment of these goals, the individual research programs involve (1) the provision of source material, (2) isolation and identification of active principles, (3) short term in vitro and in vivo biological studies to provide bioassay- directed purification capability and mechanistic information, (4) in vivo evaluations to establish efficacy, and (5) chemical synthesis, semisynthesis and structural modification to aid in the establishment of structure, mechanism and efficacy. In additional, core facilities will contribute to the Program Project in a number of ways, such as data management and biostatistical analysis. Also, databases will be utilized to aid in the establishment of structure, decrease the chance of isolating known chemopreventive entities, and predict which materials may demonstrate the desired activity. Over a period of five years, approximately 250 materials (primarily plants) will be evaluated for chemopreventive activity. Initial selections will be based on reputed activity (literature surveillance) and preliminary studies. As a result of this work, long-term contributions that are anticipated include: the development, characterization and provision of procedures for identifying dietary materials capable of preventing human cancer; the provision of heretofore unknown chemical entities that are capable of preventing human cancer; synthetic procedures that are capable of providing sufficient quantities of chemopreventive entities (or derivatives thereof) to permit more thorough evaluations in the future; mechanistic information of general value concerning the prevention of tumorigenesis. Overall, this project should provide a better understanding of the relationship between diet and cancer (cause and prevention), and establish a scientifically valid approach of comprehensively studying this relationship.

众所周知，人类癌症可能是由于接触到各种不同的 天然和合成的化学致癌物，其中许多是普遍存在的 环境污染物。相反，一些物质已经被 被确定为化学诱导的肿瘤形成的抑制物(例如， 抗氧化剂，吲哚，芳香族异硫氰酸酯，香豆素，黄酮类 二萜和维生素)。这些物质中的大多数是天然的 在人类的饮食中发生和发现的。然而，由于系统性的 探索天然产物作为化学预防药物来源的努力 从未实施过，据推测，许多利益相关的代理 仍然没有被发现。因此，我们目前提出了一个程序项目 由六个多学科的综合研究项目组成。这个 该计划项目的主要目标是鉴定、隔离和 独特癌症的特征(结构和机制) 来自天然来源的化学防护剂。为了完成…… 这些目标，个人研究方案涉及(1)提供 来源材料，(2)有效成分的分离和鉴定，(3) 短期的体外和体内生物学研究，以提供生物测定- 定向纯化能力和机制信息，(4)体内 评估以确定疗效，以及(5)化学合成， 半合成和结构修饰以帮助建立 结构、机制和功效。此外，核心设施将 以多种方式为计划项目做出贡献，例如数据 管理和生物统计分析。此外，还将利用数据库 帮助建立结构，减少隔离的机会 已知的化学预防实体，并预测哪些材料可能证明 想要的活动。在五年的时间里，大约250 将对材料(主要是植物)进行化学预防评估 活动。最初的选择将基于著名的活动(文献 监测)和初步研究。作为这项工作的结果，长期 预期的贡献包括：发展， 确定膳食的特征和程序的规定 能够预防人类癌症的材料；迄今为止提供的 能够预防人类癌症的未知化学物质； 合成程序能够提供足够数量的 化学预防实体(或其衍生物)允许更彻底 未来评估；一般价值的机械性信息 关于预防肿瘤发生的问题。总体而言，这个项目应该 更好地了解饮食与癌症之间的关系 (原因和预防)，并建立科学有效的方法 全面研究这一关系。