Green tea catechins in precancerorus prevention

绿茶儿茶素预防癌前病变

• 批准号: 7682931
• 负责人: Hwa-Chain Robert Wang
• 金额: $ 19.06万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7682931
• 关键词: Address; Benzo(a)pyrene; Biochemical; Biological; Breast; Breast Cancer Prevention; Butanones; Cancer Etiology; Cancerous; Carcinogens; Cell model; Cells; Chronic; Clinical Research; Diet; Diet Habits; Disease; Dose; Effectiveness; Environmental Carcinogens; Environmental Pollution; Environmental Risk Factor; Epidemiologic Studies; Epigallocatechin Gallate; Epithelial Cells; Exposure to; Gene Expression; Gene Mutation; Genes; Goals; Green tea; Health; Human; Individual; Malignant Neoplasms; Metabolic; Microarray Analysis; Molecular; Noninfiltrating Intraductal Carcinoma; Play; Polymerase Chain Reaction; Premalignant; Premalignant Cell; Prevention; Preventive; Process; Property; Reporting; Research; Risk; Role; Societies; Staging; System; Testing; Time; Work; cDNA Arrays; cancer prevention; carcinogenesis; cell transformation; chemical carcinogen; cost; design; dietary constituent; dietary supplements; exposed human population; innovation; loss of function; malignant breast neoplasm; prevent; public health relevance; success; transcriptomics

DESCRIPTION (provided by applicant): The goal of this project is to identify effective constituents and mechanisms of green tea catechins (GTCs) in precancerous prevention of human breast cancers associated with long-term exposures to environmental carcinogens. Carcinogenesis of breast epithelial cells from non-cancerous to precancerous and cancerous stages is a multi-year, multi-step, and multi-path disease process with progressive genetic mutations. Environmental factors (exposures to chemical carcinogens, dietary habits, etc.) are part of that process and are responsible for more than 70% of human breast cancers. Clinically, the transformed breast cells involved in ductal carcinoma-in-situ (DCIS) are precancerous and can either develop into or raise the risk of invasive breast cancer. Therefore, it is important to develop effective strategies to identify preventive agents that block formation of DCIS as a target endpoint for early prevention of breast cancers. We have developed a precancerous cellular model that verifies the potency of carcinogens that cause breast cells to acquire distinct cancerous properties in an accumulative, stepwise, and exposure-dependent manner, mimicking formation of DCIS in culture. Epidemiologic studies have suggested that GTCs may prevent breast cancer. However, the abilities of GTCs to block precancerous carcinogenesis of human breast cells have not been addressed, representing a serious gap in our understanding of the use of green tea to prevent these types of human breast cancers. Our central hypothesis is that the carcinogen-induced cancerous properties can be used as target endpoints for identification of GTC constituents and mechanisms in suppressing carcinogenesis of human breast cells. To address this hypothesis, we will use our cellular system to: 1) identify GTC constituents that block biological and biochemical target endpoints, and 2) identify transcriptomic target endpoints for GTCs in the prevention of precancerous carcinogenesis of breast epithelial cells. Success of this project will lay the groundwork for identifying biological, biochemical, metabolic, and molecular mechanisms for GTCs in the prevention of precancerous carcinogenesis of breast cells, and formulating designs for the clinical studies of dietary agents in the precancerous prevention of human cancers caused by environmental carcinogens. Our paradigm serves as a new, time- and cost-efficient approach for identifying dietary agents that are capable of blocking precancerous carcinogenesis of human breast epithelial cells and delineating their mechanisms for prevention of carcinogenesis. The broad impact of this project will benefit the whole of society by scientifically identifying active dietary agents to be used to formulate diets and dietary supplements that reduce the health risk of breast cancer and other cancers resulting from long-term exposure to carcinogens in environmental pollution. PUBLIC HEALTH RELEVANCE:Our paradigm serves as a new, time- and cost-efficient approach for identifying dietary agents that are capable of blocking precancerous carcinogenesis of human breast epithelial cells and delineating their mechanisms for prevention of carcinogenesis. The broad impact of this project will benefit the whole of society by scientifically identifying active dietary agents to be used to formulate diets and dietary supplements that reduce the health risk of breast cancer and other cancers resulting from long-term exposure to carcinogens in environmental pollution.

描述（由申请人提供）：该项目的目标是确定绿茶儿茶素（GTC）在与长期暴露于环境致癌物相关的人类乳腺癌的癌前预防中的有效成分和机制。乳腺上皮细胞从非癌变到癌前期和癌变阶段的癌变过程是一个多年、多步骤、多途径的疾病过程，伴随着渐进的基因突变。环境因素（接触化学致癌物、饮食习惯等）是这一过程的一部分，并且导致 70% 以上的人类乳腺癌。临床上，参与导管原位癌 (DCIS) 的转化乳腺细胞是癌前细胞，可能发展为浸润性乳腺癌或增加浸润性乳腺癌的风险。因此，制定有效的策略来确定阻止 DCIS 形成的预防药物作为早期预防乳腺癌的目标终点非常重要。我们开发了一种癌前细胞模型，可验证致癌物的效力，这些致癌物会导致乳腺细胞以累积、逐步和暴露依赖性的方式获得独特的癌特性，模拟培养中 DCIS 的形成。流行病学研究表明 GTC 可以预防乳腺癌。然而，GTC 阻止人类乳腺癌细胞癌前致癌作用的能力尚未得到解决，这表明我们对使用绿茶预防此类人类乳腺癌的理解存在严重差距。我们的中心假设是，致癌物诱发的癌特性可以作为目标终点，用于鉴定 GTC 成分和抑制人类乳腺细胞癌变的机制。为了解决这一假设，我们将使用我们的细胞系统：1）识别阻断生物和生化目标终点的 GTC 成分，2）识别 GTC 在预防乳腺上皮细胞癌前癌变中的转录组目标终点。该项目的成功将为确定GTC预防乳腺细胞癌前癌变的生物学、生化、代谢和分子机制奠定基础，并为膳食制剂预防乳腺癌引起的人类癌症的临床研究设计设计。环境致癌物。我们的范例是一种新的、时间和成本效益高的方法，用于识别能够阻止人类乳腺上皮细胞癌前致癌作用的饮食制剂，并描述其预防致癌作用的机制。该项目的广泛影响将使整个社会受益，通过科学地识别用于配制饮食和膳食补充剂的活性膳食制剂，降低因长期接触环境污染中的致癌物质而导致乳腺癌和其他癌症的健康风险。公共健康相关性：我们的范例是一种新的、时间和成本效益高的方法，用于识别能够阻止人类乳腺上皮细胞癌前癌变的膳食制剂，并描述其预防癌变的机制。该项目的广泛影响将使整个社会受益，通过科学地识别用于配制饮食和膳食补充剂的活性膳食制剂，降低因长期接触环境污染中的致癌物质而导致乳腺癌和其他癌症的健康风险。

项目成果

Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

干预2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶长期诱导的人乳腺细胞癌变。

• 发表时间: 2012-04
• 影响因子: 4.7
• 作者: Choudhary, Shambhunath;Sood, Shilpa;Donnell, Robert L;Wang, Hwa
• 通讯作者: Wang, Hwa

Dipyridamole intervention of breast cell carcinogenesis.

双嘧达莫干预乳腺细胞癌变。

• 发表时间: 2014-03
• 影响因子: 4.6
• 作者: Choudhary, Shambhunath;Sood, Shilpa;Wang, Hwa
• 通讯作者: Wang, Hwa

Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin.

三氯卡班诱导人乳腺细胞癌变及姜黄素干预。

• 发表时间: 2013-09-06
• 影响因子: 3.1
• 作者: Sood, Shilpa;Choudhary, Shambhunath;Wang, Hwa
• 通讯作者: Wang, Hwa