Research Project
7491024
DESCRIPTION (provided by applicant): The cancer inhibitory action by a variety of nutrients and nonnutritive components derived from food has been confirmed in numerous experimental models & has led to an increased emphasis on cancer prevention strategies in which these dietary factors are utilized. Because of their expected safety & since they are not perceived as "medicine", food-derived products may find wide-spread long-term use in the general population; thus they have been highly sought for development as chemopreventive agents. Resveratrol is one such agent that has been identified as an excellent candidate for cancer prevention. Similarly, vitamin D 1alpha(OH)D3 has demonstrated chemopreventive and growth inhibitory actions in several experimental models. However, one major limitation with the use of 1alpha(OH)D3 is that the concentration needed to induce chemopreventive effects also induces hypercalcemia. As a result, several vitamin D analogs have been synthesized. Our laboratory synthesized an analog of vitamin D 1alpha(OH)D5 and since then has shown its efficacy in several experimental models. For this application, the preliminary data supporting the use of 1alpha(OH)D5 and resveratrol against colon cancer is presented. The objectives of this application are: (1) to use a molecular-based approach to delineate the mechanisms of action of these two promising chemopreventive agents, (2) to establish the efficacy of resveratrol and 1alpha(OH)D5 in a chemically-induced colon cancer model, and (3) to investigate whether the combination of resveratrol and 1alpha(OH)D5 5 has a greater chemopreventive effect over the montherapeutic appoarch. The overall hypothesis is that the combination of resveratrol and 1alpha(OH)D5 will serve to be more effective than the monotherapeutic approach. The goal is to increase the understanding of how food derived agents modulate cancer risk at the molecular level so that eventually evidence-based strategies for cancer prevention by dietary modification can be developed. This objective denotes the career goal of the candidate. The long-term goal is to focus on diet-related cancer research within an academic setting. As a dietitian with a PhD in Nutrition & postdoctoral training in chemoprevention, the candidate seeks to investigate the basic molecular and genetic mechanisms by which nutrients influence the different step of carcinogenesis. The career development award would provide the candidate with an opportunity to enhance her understanding of molecular biology & guide her to design more molecular-based studies. Given the supportive research environment at the University, the extensive mentodng experience & expertise in the areas of chemoprevention & molecular biology by the mentors, the candidate will be better prepared to develop an independent competitive cancer research program.
