Project Number: 1950-51000-064-06
Project Type: Specific Cooperative Agreement

Start Date: Oct 01, 2006
End Date: Sep 30, 2011

Objective:
LAB:Cancer Biology To establish the dose response effects of lycopene in plasma and lung tissue with and without smoke exposure. To establish the potential for lycopene inhibition of smoke-induced lung lesions and mechanism(s) of action. To characterize both the expression and activity of carotene 9', 10'-monooxygenase in the metabolism of lycopene with and without smoke exposure, and the biological effect of the metabolite(s) of lycopene.

Approach:
LAB:Nutrition and Cancer Biology We will investigate the chemopreventive efficacy of lycopene against lung and prostate carcinogenesis in a ferret model (which is highly analogous to humans) under a variety of different circumstances (low and high doses of lycopene, with and without exposure to tobacco smoke, lung vs. prostate). We then would like to extend our work to an in vitro cell culture model, which allows in-depth mechanistic studies and examines whether the induction of IGFBP-3 with lycopene or its metabolites affect kinase activity in the IGF-I/Ras/PI3K/Akt or MAP Kinase pathways. Lastly, we will examine lycopene metabolism in different tissues (lung, liver, prostate, colon and stomach) and in the lycopene treated lung cells (normal cells vs. transformed cells) by examining carotene 9',10'-monooxygnase expression/function and its regulation by varying treatments.