Avocado in cancer prevention

描述(申请人提供)：本提案旨在明确鳄梨植物化学物质抑制口腔癌发展的功效和机制，以及体内相关调控途径的调节。根据我们的初步和已发表的数据，我们假设鳄梨肉及其提取物在体内通过ROS介导的机制防止口腔鳞状细胞癌的形成。在包括HPV转化的原代、癌前和恶性口腔细胞系在内的癌前和恶性哺乳动物细胞中发现了高基础水平的ROS。这被认为是由于代谢活动增加所致。然而，内源性ROS水平的增加似乎对这些细胞是有毒的。从鳄梨肉中分离出的D003提取物(氯仿部分)选择性地增强HPV转化的原代、癌前和恶性口腔细胞株的ROS水平并诱导其凋亡，但不能诱导正常原代细胞的凋亡。我们的初步数据还显示，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。冷冻干燥牛油果肉可预防DMBA诱发的仓鼠颊囊口腔癌的形成。我们假设，在体内调节ROS将导致抑制/预防口腔癌的发展。这一假说将在金黄地鼠颊囊模型中得到解决，具体目的如下：i)确定整个鳄梨肉和D003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经鳄梨肉和D003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，为鳄梨预防口腔癌奠定科学基础。这些新的研究将首次考察鳄梨果预防口腔癌的体内效应以及鳄梨果对口腔粘膜的分子作用。目前的研究将对口腔癌的化学预防作用和鳄梨果在未来抑制高危人群癌前和癌症结果的临床试验中的有用性提供明确的评估。

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.