Dietary Prevention of Cancer

描述（由申请人提供）：结肠癌是美国的主要死亡原因。因此，预防这种疾病的方法或发现增加现有化疗药物有效性的药物将是非常有益的。我们的研究和其他人的研究表明，姜黄素是香料姜黄中的一种活性成分，可以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构成了肿瘤生长和转移潜能的主要途径。我们的初步研究表明，姜黄素抑制细胞增殖，抑制肿瘤血管生成和侵袭性，同时增强肿瘤细胞自发和化疗诱导的凋亡。当前项目的目标是确定姜黄素在这些过程中的作用机制。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前列腺素介导的信号传导中的作用，这两种分子在癌症进展中是活跃的。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p21、WAF1、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表达中的作用，以及作为肿瘤侵袭调节因子的基质金属蛋白酶。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定义遗传操作的结果。综上所述，这些研究应该能让我们深入了解癌症的发生过程以及姜黄素如何抑制结肠癌的风险和增殖，同样重要的是，为什么姜黄素作为一种食物补充剂具有巨大的价值。

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.