Project Funding Details

Background. At the time of the 2007 AICR report, foods containing lycopene met the criteria for a probable reduction in risk, and since then, pre-clinical studies continue to substantiate the relationships between lycopene-containing tomato foods with a reduced prostate cancer risk. As we continue study tomatoes and prostate cancer, we are also laying the groundwork for rationally-designed clinical trials by developing an optimized, defined, and reproducible tomato test juice and testing it in phase I & II clinical trials. As we continue to refine the formulation, a potentially superior, tangerine variety of tomato, has emerged, which is a rich source of highly bioavailable tetra-cis-lycopene and other carotenoids. To determine whether this tomato deserves further clinical evaluation, we must first test its efficacy and biological impacts in a rodent model of prostate cancer in comparison to standard, red tomato. Objectives. Aim 1.) To compare tangerine and red tomato with control-diet feeding on prostate cancer incidence and severity in the TRAMP model of prostate carcinogenesis. Aim 2.) To compare the biological impacts of tangerine vs. red tomato feeding in early prostate carcinogenesis. Setting & Methods. All procedures and analyses will be performed at the Ohio State University Comprehensive Cancer Center (OSUCCC). Aim 1.) TRAMP mice will be fed 1 of 3 experimental, macronutrient-balanced experimental diets containing either 10% red or 10% tangerine tomato powder, or neither (control) (n=30/group) from weaning to 18-wk (when 100% of control group will have histological cancer lesions). At 18 wk, mice will be sacrificed, and specimens will be collected. Total, histologically-defined prostate cancer incidence and severity and differences in carotenoid and metabolite serum concentrations (by HPLC-MS) will be compared between groups. Aim 2.) To study the impacts of tangerine vs. red tomato on early cellular and molecular carcinogenesis, mice will be fed 1 of the 3 test diets described in Aim 1 (n=15/group) from weaning to10 wk, when 100% of control group will have early prostatic intraepithelial neoplastic lesions. Prostatic histological assessments will be integrated with prostatic transcriptomic (Nanostring) and protein biomarker analyses to reveal the molecular pathways (Ingenuity Pathway Analysis) impacted by feeding tangerine or red tomato. Potential Impact. Evidence suggesting tangerine tomatoes are as or more effective than red tomatoes in reducing prostate carcinogenesis would provide rationale for or against testing tangerine tomato-based food products in clinical trials of prostate cancer prevention. Keywords. Prostate cancer, tomato, TRAMP, lycopene, carotenoids, carcinogenesis, chemoprevention

Background. In 2007, the AICR/WCRF report stated that foods containing lycopene met the criteria for a probable reduction in prostate cancer risk. Indeed, this was reported as the strongest relationship linking any dietary variable with prostate cancer risk. Since then, numerous laboratory studies found that lycopene-containing tomato foods reduce prostate cancer in animal models. As we continue laboratory studies of how to best utilize this knowledge and translate the experimental findings into human studies, we have several key issues to resolve. We are developing a fully-defined and reproducible tomato-based vegetable juice for human studies. We have recently completed studies of absorption and distribution of these bioactives to the prostate from our OSU-Tomato Soy Juice. We continue to refine the formulation based upon scientific evidence. Most critically, we have found that bioactive phytochemicals are more readily absorbed if the chemical structure of lycopene is in one of several cis-isomer configurations. Tangerine tomatoes are an orange variety of tomato available currently at most supermarkets, and are a particularly rich source of cis-lycopene. In addition to containing highly absorbable lycopene, tangerine tomatoes also are a rich source of other highly absorbable tomato carotenoids, including phytoene. To determine if tangerine tomatoes deserve further clinical evaluation, we must first test their activity in a rodent model of prostate cancer in comparison with standard, red tomatoes. Objectives. Aim 1.) To determine if the efficacy of tangerine tomato consumption for prostate cancer incidence reduction compared to control or red tomato-containing diets. Aim 2.) To determine if tangerine tomatoes have the same or better impact than red tomatoes on inhibiting early cancer processes. Potential Impact. Evidence suggesting that tangerine tomatoes have a similar or greater impact on prostate carcinogenesis will change our direction for future translational research. Our goal is to utilize this information to better design our tomato juice for future clinical trials of prostate cancer prevention and attenuation. Keywords. Prostate cancer, tomato, lycopene, carotenoids, carcinogenesis, chemoprevention