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Determine the extent to which the endpoint of ultimate relevance--the development of obesity-associated colorectal neoplasms--is inhibited by the combination of vitamin B6 and curcumin, and begin to define an optimally effective tumor-suppressive dose of this combination regimen.By using a factorial design, delineate the relative chemopreventive potencies of vitamin B6 and curcumin as individual agents, and compare the extent to which combining the two offers multiplicative protection against obesity-promoted tumorigenesis.Examine whether packaging the B6 and curcumin in a novel nanoparticle system that targets delivery to the colon potentiates the tumor-suppressive properties of the combination regimen, thereby improving the efficacy of cancer prevention and diminishing the required amounts of curcumin and B6.
Obesity substantially increases the risk of colorectal cancer, and a major avenue through which this effect appears to be mediated is the low-grade state of inflammation it produces. The central goal of this application is to delineate a means of preventing these obesity-promoted cancers using a novel dietary regimen consisting of two bioactive food components that have established anti-inflammatory effects--vitamin B6 and curcumin.We aim to promote gastrointestinal health by investigating the anti-inflammatory, cancer preventive properties of this combination of two bioactive components found in food. Further, we aim to improve the health value of food by developing an innovative nanoparticle packaging technology that directs the delivery of the curcumin and B6 to the colonic mucosa, thereby fortifying the cancer preventive properties of this regimen. To accomplish our goals we propose the following supporting objectives, to be conducted in well-established mouse models: Determine the extent to which obesity-promoted colorectal tumorigenesis is inhibited by the combination of vitamin B6 and curcumin, and define an optimally effective tumor-suppressive dose of this combination regimen. Delineate the relative chemopreventive potencies of vitamin B6 and curcumin as individual agents, and compare the extent to which combining the two offers multiplicative protection against tumorigenesis. Examine whether packaging the B6 and curcumin in a novel colon-targeting nanoparticle system potentiates the tumor-suppressive properties of the combination regimen.