Avocado in cancer prevention

描述（由申请人提供）：本提案旨在确定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。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通过ros介导的机制在体内阻止口腔鳞状细胞癌的形成。在人乳头瘤病毒转化的原发、癌前和恶性口腔细胞系中发现了高基础水平的ROS。这被认为是由于代谢活动的增加。然而，从内源性来源增加ROS水平似乎对这些细胞有毒。从鳄梨肉中分离的D003提取物（氯仿部分）选择性地提高了人hpv转化的原代、癌前和恶性口腔细胞系的ROS水平，并诱导细胞凋亡，但对正常的原代细胞没有作用。我们的初步数据还表明，鳄梨肉的整个鳄梨提取物增加ROS水平，抑制恶性和恶性人类口腔上皮细胞系的增殖。冻干鳄梨肉防止dba诱导的仓鼠颊袋模型口腔癌的形成。我们假设在体内调节ROS将导致抑制/预防口腔癌的发展。这一假设将在仓鼠颊袋模型中得到验证，具体目的如下：i)确定整个鳄梨肉和D003提取物防止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D003提取物对细胞内ROS水平的影响在体内对口腔肿瘤的预防作用。这些研究将为今后的临床试验提供有价值的信息。

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.