The overall research focus of the collaborative team from the University of Illinois and The Ohio State University has been to determine the impact of tomatoes and their bioactive components, especially lycopene, on prostate carcinogenesis. Prostate cancer is the most common cancer in American men and dietary approaches that reduce risk, or delay onset, would have profound impact on public health. Epidemiological and animal studies suggest that consumption of tomato products reduces the risk of prostate cancer. We propose to carry out studies in transgenic mice to determine if the tomato carotenoids, lycopene, phytoene, and phytofluene, or their metabolic products reduce the risk of development and progression of prostate cancer. In order to answer the questions raised in this proposal, we will utilize two new mouse strains that lack one of the two known mammalian carotenoid cleavage enzymes, carotenoid 15, 15'monooxygenase (CMO-I) and carotenoid 9', 10'monooxygenase (CMO-II). The three major specific aims are: 1) delineate the tissue-specific expression of CMO-I and CMO-II in A) wild-type, CMO-I knockout (KO), and CMO-II KO mice in response to short (3 days) and long term (30 days) feeding of different levels of tomato powder or lycopene, and in B) TRAMP mice during the development of carcinogenesis, 2) precisely determine how changes in CMO-I and CMO-II expression dictate A) tissue biodistribution of tomato carotenoids, and B) production of lycopenoids and other tomato carotenoid metabolites, and 3) to investigate the effect of altered tomato carotenoid metabolism on prostate cancer by A) creating double transgenic mice and B) differentiating the ability of dietary tomato powder and lycopene to inhibit prostate cancinogenesis in TRAMP, TRAMP X CMO-I KO, and TRAMP X CMO-II KO mice. We are uniquely qualified to carry out the proposed studies due to our broad expertise with carotenoids and cancer models, access to CMO-I KO and II KO mice, and our ability to biosynthesize radiolabeled tomato carotenoids using tomato cell suspension culture. Our continuing hypothesis is that genetic polymorphisms involved in metabolism of carotenoids, such as CMO-I and II, are critical determinants of the benefits of tomato products against prostate carcinogenesis in humans. These studies will allow us to determine if tomato carotenoids, or their metabolic products, are able to prevent or counteract the development of prostate cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA125384-03
Application #
7666786
Study Section
Chemo/Dietary Prevention Study Section (CDP)
Program Officer
Kim, Young S
Project Start
2007-09-20
Project End
2012-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
3
Fiscal Year
2009
Total Cost
$287,289
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Nutrition
Type
Schools of Earth Sciences/Natur
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Tan, Hsueh-Li; Thomas-Ahner, Jennifer M; Moran, Nancy E et al. (2017) ?-Carotene 9',10' Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model. Cancer Prev Res (Phila) 10:161-169
Smith, Joshua W; Ford, Nikki A; Thomas-Ahner, Jennifer M et al. (2016) Mice lacking ?-carotene-15,15'-dioxygenase exhibit reduced serum testosterone, prostatic androgen receptor signaling, and prostatic cellular proliferation. Am J Physiol Regul Integr Comp Physiol 311:R1135-R1148
Tan, Hsueh-Li; Moran, Nancy E; Cichon, Morgan J et al. (2014) ?-Carotene-9',10'-oxygenase status modulates the impact of dietary tomato and lycopene on hepatic nuclear receptor-, stress-, and metabolism-related gene expression in mice. J Nutr 144:431-9
Wan, Lei; Tan, Hsueh-Li; Thomas-Ahner, Jennifer M et al. (2014) Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis. Cancer Prev Res (Phila) 7:1228-39
Erdman Jr, John W; Jeffery, Elizabeth; Hendrickx, Marc et al. (2014) Can Food Processing Enhance Cancer Protection? Nutr Today 49:230-234
Moran, Nancy Engelmann; Clinton, Steven K; Erdman Jr, John W (2013) Differential bioavailability, clearance, and tissue distribution of the acyclic tomato carotenoids lycopene and phytoene in mongolian gerbils. J Nutr 143:1920-6
Zuniga, Krystle E; Clinton, Steven K; Erdman Jr, John W (2013) The interactions of dietary tomato powder and soy germ on prostate carcinogenesis in the TRAMP model. Cancer Prev Res (Phila) 6:548-57
Ford, Nikki A; Elsen, Amy C; Erdman Jr, John W (2013) Genetic ablation of carotene oxygenases and consumption of lycopene or tomato powder diets modulate carotenoid and lipid metabolism in mice. Nutr Res 33:733-42
Ford, Nikki A; Erdman Jr, John W (2012) Are lycopene metabolites metabolically active? Acta Biochim Pol 59:1-4
Ford, Nikki A; Moran, Nancy Engelmann; Smith, Joshua W et al. (2012) An interaction between carotene-15,15'-monooxygenase expression and consumption of a tomato or lycopene-containing diet impacts serum and testicular testosterone. Int J Cancer 131:E143-8

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