Dietary interventions for reduction of prostate carcinogenesis in rodent models

Zuniga, Krystle

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https://hdl.handle.net/2142/44765 Copy

Description

Title

Dietary interventions for reduction of prostate carcinogenesis in rodent models

Author(s)

Zuniga, Krystle

Issue Date

2013-05-28T19:19:00Z

Director of Research (if dissertation) or Advisor (if thesis)

Erdman, John W.

Doctoral Committee Chair(s)

de Mejia, Elvira G.

Committee Member(s)

• Erdman, John W.
• Jeffery, Elizabeth H.
• Wallig, Matthew A.

Department of Study

Nutritional Sciences

Discipline

Nutritional Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• prostate cancer
• tomato
• soy
• lycopene
• isoflavones
• animal models
• broccoli

Abstract

Prostate cancer (PCa) is the second leading cause of cancer and cancer related deaths in U.S. men; thus, identifying strategies to reduce PCa incidence could have a significant impact on public health. Epidemiological studies have supported the hypotheses that dietary intake of soy foods or tomato products is associated with a reduced risk of PCa. The efficacy of combinations of foods and bioactives for enhanced health benefits is of clinical interest, but the interactions between foods rich in bioactives for the inhibition of PCa are largely unknown. To evaluate the bioavailability of tomato carotenoids and soy germ isoflavones when consumed alone or together, male Copenhagen rats were randomized to consume: AIN-93G control, 10% tomato powder (TP), 2% soy germ (SG) or 10% tomato powder + 2% soy germ (TP+SG) for 7 days or 25 weeks. In the 7-day trial, rats consuming TP+SG had significantly lower serum phytoene, phytofluene, and lycopene compared to rats consuming TP alone (p<0.05). In the 25-week trial, lycopene bioaccumulation was significantly lower in the testes, seminal vesicles and ventral prostate of rats that consumed TP+SG compared to TP alone (p<0.05). Reduced carotenoid bioaccumulation was not explained by mRNA expression of scavenger receptor class B type I (a protein involved in carotenoid absorption) or carotenoid metabolizing enzymes in the prostate, liver or duodenal mucosa. Hepatic lipid accumulation and serum cholesterol were not significantly different between groups, suggesting that differences in carotenoid bioaccumulation were likely not due to effects on intestinal micellerization or lipid absorption. Significantly higher urinary isoflavone excretion in the TP+SG group compared to the SG group was not explained by differences in activity or expression of hepatic detoxification enzymes. Soy isoflavones and tomato carotenoids have distinctly different mechanisms of absorption, yet, long-term combined consumption of TP+SG resulted in reduced carotenoid bioaccumulation and increased urinary isoflavone excretion than when each food was consumed separately. After identifying a food-food interaction in the bioavailability study, the efficacy of dietary tomato and soy germ, alone and in combination, for the inhibition of PCa was evaluated in the TRAMP model of PCa. At 4 weeks of age, male TRAMP mice were randomized to consume: AIN-93G control, 10% TP, 2% SG or TP+SG for 14 weeks. Serum and testicular lycopene concentrations were significantly lower in TP+SG fed mice compared to mice fed TP alone, supporting our previous finding of reduction of carotenoid bioavailability by consumption of SG. Equol, produced from the metabolism of daidzein by intestinal microbiota, was the predominant isoflavone in the serum and prostate in SG fed mice. 100% of mice fed the control diet had PCa, while PCa incidence was significantly lower in mice consuming TP (61%, p<0.001), SG (66%, p<0.001) and TP+SG (45%, p<0.001). Although the protection offered by the combination of TP and SG was not synergistic, it was quantitatively the most effective intervention. Consumption of cruciferous vegetables, such as broccoli, has been suggested to reduce the risk of aggressive PCa. Clinical evidence suggests expression of markers of the epithelial-mesenchymal transition (EMT) is associated with a more invasive and aggressive PCa. The goal of the project was to investigate the effects of consumption of standard broccoli and methyl-jasmonate (MeJa) treated broccoli, a broccoli higher in bioactive, indole-glucosinolates, on expression of EMT markers in TRAMP mice with well-differentiated adenocarcinoma. Immunohistochemical analysis of E-cadherin and N-cadherin across a range of pathology in the TRAMP model suggests that the loss of E-cadherin and the gain of N-cadherin are predictive of metastasis. A trend of higher prostatic E-cadherin expression by standard broccoli (p=0.06) but not MeJa broccoli (p=0.5) was identified. Compared to control-fed TRAMP mice, prostatic mRNA expression of N-cadherin was approximately 2-fold lower in mice fed either standard (p=0.04) or MeJa (p=0.02) broccoli. MeJa broccoli did not provide any additional benefit compared to standard broccoli, suggesting that the indole-glucosinolates are not responsible for modulation of markers of EMT by broccoli. Mechanisms by which the combination of tomato and soy germ, alone and in combination, are protective against PCa or by which broccoli can modulate expression of EMT-related markers are yet to be elucidated and require further investigation. Combinations of foods such as tomato and soy germ may result in positive food-food interactions, providing added protection against prostate carcinogenesis. Whole foods, such as broccoli, may modulate the molecular profile of existing PCa, reducing the risk of cancer progression and associated mortality. Overall, our findings suggest that dietary interventions with whole foods and combinations of foods are effective and safe strategies for prevention of PCa incidence or progression in an animal model.

Graduation Semester

2013-05

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Copyright and License Information

Copyright 2013 Krystle Zuniga

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