Targeting colorectal carcinogenesis using a cinnamon-derived food factor

使用肉桂源性食物因子对抗结直肠癌

基本信息

批准号：
8442671
负责人：
Georg T Wondrak
金额：
$ 19.77万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8442671
关键词：
Animals Antioxidants Biochemical Genetics Cells Chemicals Chemoprevention Chemopreventive Agent Cinnamomum cassia Cinnamon - dietary Clinical Research Colitis Colon Colorectal Colorectal Cancer Consumption Cytoprotection Data Development Diabetic Nephropathy Dietary Factors Dimensions Disease Documentation Dose Epithelial Epithelial Cells FDA approved Flavoring Food Food Additives Future Health Human Incidence Inflammation Inflammatory Intervention Knockout Mice Lesion Modeling Molecular Molecular Target Morbidity - disease rate Mus Nature Nuclear Oral Oral Administration Oxidation-Reduction Powder dose form Predisposition Proteins Proteomics Publishing Research Research Project Grants Role Safety Skin Spices Sri Lanka Staging Structure-Activity Relationship Testing Time Volatile Oils base biological adaptation to stress cancer chemoprevention carcinogenesis cinnamic aldehyde design metastatic colorectal mortality outcome forecast preclinical study prototype public health relevance response tool transcription factor tumor

项目摘要

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is a major cause of tumor-related morbidity and mortality worldwide. Recent research strongly suggests that the redox-sensitive transcription factor Nrf2 (nuclear factor-E2-related factor 2) is a promising molecular target for chemoprevention of inflammation-driven colorectal carcinogenesis. The ground bark of Cinnamomum aromaticum (cassia) and Cinnamomum verum (Ceylon cinnamon), commonly referred to as 'cinnamon', is one of the three most consumed spices in the world, yet health effects of cinnamon consumption have remained mostly unexplored at the molecular level. Recently, we have identified the cinnamon-derived food factor cinnamaldehyde as the key principle in cinnamon powder responsible for potent induction of the Nrf2-regulated antioxidant response in human colon cells, conferring cytoprotection against subsequent oxidative and genotoxic insult. We propose exploratory research that tests the overall hypothesis that cinnamaldehyde represents a potent chemopreventive dietary factor targeting colorectal carcinogenesis through modulation of Nrf2-orchestrated cytoprotective mechanisms. To test this hypothesis, the following specific aims will be pursued: Aim #1. To define the specific molecular targets involved in Nrf2-activation by cinnamaldehyde in colorectal epithelial cells. Aim #2. To test feasibility of cinnamaldehyde-based intervention targeting colorectal carcinogenesis in an accepted murine model and to determine mechanistic involvement of Nrf2 in cinnamaldehyde chemopreventive activity. Successful completion of this project will generate critical proof-of-principle data guiding the rational design of future preclinical and clinical studies that aim at developing cinnamaldehyde for chemopreventive intervention targeting human colorectal carcinogenesis.

描述（由申请人提供）：结直肠癌（CRC）是全世界肿瘤相关发病率和死亡率的主要原因。最近的研究强烈表明，氧化还原敏感转录因子 Nrf2（核因子-E2 相关因子 2）是化学预防炎症驱动的结直肠癌发生的有前途的分子靶点。肉桂 (Cinnamomumaromaticum) 和锡兰肉桂 (Cinnamomum verum) 的地皮通常被称为“肉桂”，是世界上消费量最大的三种香料之一，但食用肉桂对健康的影响在分子水平上仍未得到充分探索。等级。最近，我们发现肉桂衍生的食物因子肉桂醛是肉桂粉中的关键成分，负责在人类结肠细胞中有效诱导 Nrf2 调节的抗氧化反应，从而提供细胞保护以防止随后的氧化和基因毒性损伤。我们提出了探索性研究来测试总体假设，即肉桂醛是一种有效的化学预防饮食因素，通过调节 Nrf2 协调的细胞保护机制来靶向结直肠癌的发生。为了检验这一假设，将追求以下具体目标：目标#1。确定结直肠上皮细胞中肉桂醛激活 Nrf2 所涉及的特定分子靶标。目标#2。在公认的小鼠模型中测试基于肉桂醛的干预措施针对结直肠癌发生的可行性，并确定 Nrf2 在肉桂醛化学预防活性中的机制参与。该项目的成功完成将产生关键的原理验证数据，指导未来临床前和临床研究的合理设计，旨在开发肉桂醛用于针对人类结直肠癌发生的化学预防干预。