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Avocado in cancer prevention

鳄梨预防癌症

基本信息

批准号：
8109246
负责人：
Haiming Ding
金额：
$ 7.55万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-15 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8109246
关键词：
Address Anthracenes Apoptosis Avocado Breast Cancerous Cell Culture Techniques Cell Line Cell Proliferation Cells Cheek structure Chemopreventive Agent Chloroform Clinical Trials Consumption Data Development Epidemiologic Studies Epithelial Cells Exhibits Foundations Freeze Drying Fruit Future Growth Hamsters Human Human Papillomavirus In Situ In Vitro Individual Lead Lesion Leukoplakia Malignant - descriptor Malignant Neoplasms Mammalian Cell Meat Mediating Metabolic Modeling Molecular Mouth Neoplasms Oral Oral mucous membrane structure Outcome Papilloma Phase II Clinical Trials Phytochemical Pilot Projects Population Premalignant Premalignant Cell Prevention Preventive Prostate Public Health Publishing Recurrent tumor Regulatory Pathway Risk Role Smoker Source Staging Testing Tissues Water base cancer cell cancer prevention carcinogenesis design dimethylbenzanthracene fruits and vegetables high risk in vivo leukemia malignant mouth neoplasm mouth squamous cell carcinoma novel oral cancer prevention oral tissue pre-clinical preclinical study prevent public health relevance tumor

项目摘要

DESCRIPTION (provided by applicant): This proposal is to define the efficacy and mechanisms of avocado phytochemicals in inhibiting oral cancer development and modulation of related regulatory pathways in vivo. We hypothesize that avocado meat and its extracts prevent the formation of oral squamous cell carcinoma in vivo via a ROS-mediated mechanism based on our preliminary and published data. High basal levels of ROS have been found in premalignant and malignant mammalian cells including HPV- transformed primary, premalignant and malignant human oral cell lines. This is thought to be due to increased metabolic activity. However, increasing ROS levels from endogenous sources appears to be toxic to these cells. The D003 extract (chloroform fraction) isolated from avocado meat selectively enhances the levels of ROS and induces apoptosis in HPV-transformed primary, premalignant and malignant human oral cell lines but not normal primary cells. Our preliminary data also shows that whole avocado extract of avocado meat increases ROS levels and inhibits proliferation of the premalignant and malignant human oral epithelial cell lines. Freeze-dried avocado meat prevents DMBA-induced oral cancer formation in hamster cheek pouch model. We hypothesize that modulating ROS in vivo will lead to inhibition/prevention of oral cancer development. This hypothesis will be addressed in the hamster cheek pouch model with the following specific aims: i) Determine the ability of whole avocado meat and D003 extract to prevent the formation of oral tumors; ii) Investigate at the tissue and cellular level the role of intracellular ROS levels modified by avocado meat and D003 extract in the prevention of oral tumors in vivo. These studies will provide valuable information for future clinical trials. PUBLIC HEALTH RELEVANCE: This study will provide essential data establishing the scientific foundation for prevention of oral cancer by avocado fruit. These novel studies will be the first to examine the in vivo effect of avocado fruit on the prevention of oral cancer and molecular effects modified by avocado fruit on oral mucosa in pre-initiated oral tissues. The current study will provide a definitive assessment of the chemopreventive effects on oral cancer and the usefulness of the avocado fruit in future clinical trials for inhibition of premalignant and cancerous outcomes in high-risk populations.

描述（由申请人提供）：本提案旨在定义鳄梨植物化学物质在体内抑制口腔癌发展和调节相关调控途径的功效和机制。基于我们的初步和已发表的数据，我们假设鳄梨肉及其提取物通过ROS介导的机制在体内预防口腔鳞状细胞癌的形成。已经在癌前和恶性哺乳动物细胞中发现了高基础水平的ROS，包括HPV转化的原代、癌前和恶性人口腔细胞系。这被认为是由于代谢活动增加。然而，来自内源性来源的增加的ROS水平似乎对这些细胞是有毒的。从鳄梨肉中分离的D 003提取物（氯仿级分）选择性地增强ROS水平并诱导HPV转化的原代、癌前和恶性人类口腔细胞系中的细胞凋亡，但不诱导正常原代细胞。我们的初步数据还表明，鳄梨肉的整个鳄梨提取物增加了ROS水平，并抑制了癌前和恶性人类口腔上皮细胞系的增殖。冷冻干燥鳄梨肉预防DMBA诱导的仓鼠颊囊模型口腔癌形成。我们假设体内调节ROS将导致抑制/预防口腔癌的发展。该假设将在仓鼠颊囊模型中解决，具有以下具体目的：i）确定整个鳄梨肉和D 003提取物预防口腔肿瘤形成的能力; ii）在组织和细胞水平上研究鳄梨肉和D 003提取物修饰的细胞内ROS水平在体内预防口腔肿瘤中的作用。这些研究将为未来的临床试验提供有价值的信息。公共卫生相关性：这项研究将提供必要的数据，为鳄梨水果预防口腔癌奠定科学基础。这些新的研究将是第一个研究鳄梨果实对预防口腔癌的体内作用以及鳄梨果实对预启动口腔组织中口腔粘膜的分子作用的研究。目前的研究将提供对口腔癌的化学预防作用的明确评估，以及鳄梨果实在未来临床试验中抑制高危人群癌前病变和癌症结局的有用性。