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Dietary Prevention of Cancer

饮食预防癌症

基本信息

批准号：
7405370
负责人：
Shrikant Anant
金额：
$ 27.43万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7405370
关键词：
1-Phosphatidylinositol 3-Kinase AKT inhibition Adenocarcinoma Affect Angiogenic Factor Apoptosis Apoptosis Promoter Apoptotic Azoxymethane BAX gene Bax protein Biochemical Cause of Death Cell Proliferation Cell Survival Colon Colon Carcinoma Colonic Adenoma Cultured Cells Curcumin Development Diet Dinoprostone Disease Drug Delivery Systems Drug resistance EGF gene Effectiveness End Point Epidermal Growth Factor Epidermal Growth Factor Receptor Food Supplements Gene Targeting Genus Cola Goals Growth Growth Factor Human Hypoxia In Vitro Incidence Intestines Ligands MAPK14 gene MAPK8 gene Malignant Neoplasms Matrix Metalloproteinases Mediating Methods Molecular Mus Neoplasm Metastasis Nude Mice Pathway interactions Pharmaceutical Preparations Phosphorylation Phosphotransferases Population Preventive Process Prostaglandins Prostaglandins E Protein Kinase Protein Tyrosine Kinase Protein p53 Proto-Oncogene Proteins c-akt Rattus Receptor Protein-Tyrosine Kinases Regulation Resistance Risk Role Signal Pathway Signal Transduction Solid Neoplasm Source Specificity Spices Staging TP53 gene Therapeutic Tumeric Tumor Angiogenesis Tumor Biology Tumor Suppressor Proteins United States Vascular Endothelial Growth Factors adenoma angiogenesis cancer cell cancer prevention chemotherapeutic agent chemotherapy clinical phenotype colon cancer cell line cyclooxygenase 2 dietary constituent dietary supplements genetic manipulation in vivo insight irinotecan microbial alkaline proteinase inhibitor migration mutant neoplastic cell neovascularization novel oncoprotein p21 polyphenol prevent receptor response transcription factor tumor tumor progression tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Colon Cancer is a leading cause of death in the United States. Accordingly, methods of preventing this disease or discovery of agents that increase effectiveness of existing chemotherapeutic agents would be very beneficial. Our studies and those of others have indicated that dietary curcumin, an active ingredient in the spice turmeric, potently inhibits intestinal tumorigenesis. We have now characterized the mechanisms by which curcumin modulates this function. Proliferation, angiogenesis and tumor invasiveness constitute the major pathways that are necessary for the growth and metastatic potential of cancer. Our preliminary studies show that curcumin inhibits cell proliferation, and tumor angiogenesis and invasiveness, while it enhances spontaneous and chemotherapy-induced apoptosis of tumor cells. The goals of the current project are to determine the mechanistic effects of curcumin on each of theses processes. Specifically, we will determine the effects of curcumin on growth factor-mediated activation of cellular signaling pathways. We will also determine the role of curcumin in signaling mediated by epidermal growth factor and prostaglandins, two molecules that are active in cancer progression. In addition, we will determine the effect of curcumin on the expression and regulation of tumor suppressor protein p53, an important regulator of cell survival. We will examine the effect of curcumin on expression of p53 target genes such as p21 WAF1, BAX. Moreover, we will examine the role of curcumin in the expression of VEGF and related angiogenesis factors as well as matrix metalloproteinases as regulators of tumor invasiveness. We will compare the results obtained in cell culture studies with that observed in mice with defined genetic manipulations. Together these studies should provide insight into the cancer process and how curcumin suppresses the risk and proliferation of colon cancer, and of no less importance, why curcumin is of great value as a food supplement.

描述（由申请人提供）：结肠癌是美国的主要死因。因此，预防这种疾病的方法或发现增加现有化疗剂有效性的药剂将是非常有益的。我们和其他人的研究表明，饮食姜黄素，香料姜黄中的活性成分，有效地抑制肠道肿瘤的发生。我们现在已经描述了姜黄素调节这一功能的机制。增殖、血管生成和肿瘤侵袭性构成了癌症生长和转移潜力所必需的主要途径。我们的初步研究表明，姜黄素抑制细胞增殖，肿瘤血管生成和侵袭，同时它增强自发和化疗诱导的肿瘤细胞凋亡。目前项目的目标是确定姜黄素对这些过程中的每一个的机械作用。具体来说，我们将确定姜黄素对生长因子介导的细胞信号通路激活的影响。我们还将确定姜黄素在表皮生长因子和胡萝卜素介导的信号传导中的作用，这两种分子在癌症进展中具有活性。此外，我们将确定姜黄素对肿瘤抑制蛋白p53的表达和调节的影响，p53是细胞存活的重要调节因子。我们将研究姜黄素对p53靶基因如p21 WAF 1，BAX表达的影响。此外，我们将研究姜黄素在VEGF和相关血管生成因子以及基质金属蛋白酶作为肿瘤侵袭调节因子的表达中的作用。我们将比较在细胞培养研究中获得的结果与在小鼠中观察到的确定的遗传操作。总之，这些研究应该提供深入了解癌症过程以及姜黄素如何抑制结肠癌的风险和增殖，以及同样重要的是，为什么姜黄素作为食品补充剂具有巨大价值。