The interactions between bioactive rich food components within a complex human diet for the inhibition of prostate carcinogenesis (PCa) are largely unknown and difficult to quantify in humans. Tomato and soy products have each shown anti-PCa activity in laboratory studies. The objective of this study was to determine the efficacy of dietary tomato and soy germ, alone and in combination, for the inhibition of prostate carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. At 4 weeks of age, male C57BL/6 x FVB TRAMP mice (n=119) were randomized to consume: AIN-93G control, 10% whole tomato powder (TP), 2% soy germ powder (SG) or 10% tomato powder with 2% soy germ powder (TP+SG) for 14 weeks. 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 the most effective intervention. TP, SG and TP+SG increased apoptotic index (AI) and modestly reduced the proliferative index (PI) in the prostate epithelium of TRAMP mice exhibiting primarily prostatic intraepithelial neoplasia. The dramatic reduction in the PI/AI ratio by the dietary interventions suggests that the control mice experience a stronger stimulus for malignant progression in the prostate microenvironment. Maximally effective and safe strategies for PCa prevention may result from optimizing combinations of nutrients and bioactives through an orchestration of dietary patterns.
"We found the weakest response to dutasteride in the ventral lobe. Another study that used the same scoring system also found fewer statistical differences in the ventral lobe in response to tomato powder and soy germ diets, especially compared with the dorsal and lateral lobes . This decrease in efficacy in the ventral lobe might be explained by the fact that in large probasin-large T antigen mice, dutasteride markedly decreased the dorsolateral prostate weights but had little to no effect on ventral prostate weights . "
[Show abstract][Hide abstract] ABSTRACT: The prostate cancer prevention trial (PCPT) and Reduction by dutasteride of Prostate Cancer Events (REDUCE) trial found that 5α-reductase (5αR) inhibitors finasteride and dutasteride respectively, decreased prostate cancer prevalence but also increased the incidence of high-grade tumors. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have high 5αR1 and low 5αR2 expression. Because finasteride inhibits only 5αR2, we hypothesized that it would not be as efficacious in preventing prostate cancer development and/or progression in C57BL/6 TRAMP x FVB mice as dutasteride, which inhibits both 5αR1 and 5αR2.
Six-week-old C57BL/6 TRAMP x FVB male mice were randomized to AIN93G control or pre- and post- finasteride and dutasteride diet (83.3 mg drug/kg diet) groups (n =30-33) that began at 6 and 12 weeks of age, respectively, and were terminated at 20 weeks of age. The pre- and post- finasteride and dutasteride groups were designed to test the preventive and therapeutic efficacy of the drugs, respectively. Final body weights, genitourinary tract weights, and genitourinary tract weights as percentage of body weights were significantly decreased in the Pre- and Post-dutasteride groups compared with the control. The Post-dutasteride group showed the greatest inhibition of prostatic intraepithelial neoplasia progression and prostate cancer development. Surprisingly, the Post-dutasteride group showed improved outcomes compared with the Pre-dutasteride group, which had increased incidence of high-grade carcinoma as the most common and most severe lesions in a majority of prostate lobes. Consistent with our hypothesis, we found little benefit from the finasteride diets, and they increased the incidence of high-grade carcinoma.
Our findings have commonalities with previously reported PCPT, REDUCE, and the Reduction by dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial results. Our results may support the therapeutic use of dutasteride, but not finasteride, for therapeutic or preventive use.
PLoS ONE 10/2013; 8(10):e77738. DOI:10.1371/journal.pone.0077738 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tomatoes produce the bioactive compounds lycopene and α-tomatine that are reported to have potential health-promoting effects in animals and humans, but our understanding of the roles of these compounds in the diet is incomplete. Our current knowledge gained from the chemistry and analysis of these compounds in fresh and processed tomatoes and from studies on their bioavailability, bioactivity, and mechanisms of action against cancer cells and other beneficial bioactivities including antibiotic, anti-inflammatory, antioxidative, cardiovascular, and immunostimulating effects in cells, animals, and humans is discussed and interpreted here. Areas for future research are also suggested. The collated information and suggested research might contribute to a better understanding of the agronomical, biochemical, chemical, physiological, molecular, and cellular bases of the health-promoting effects and facilitate and guide further studies needed to optimize the use of lycopene and α-tomatine in pure form and in fresh tomatoes and processed tomato products to help prevent or treat human disease.
Journal of Agricultural and Food Chemistry 09/2013; 61(40). DOI:10.1021/jf402654e · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tomato and lycopene (ψ, ψ-carotene) consumption is hypothesized to protect against nonalcoholic steatohepatitis and hepatocarcinogenesis, processes that may depend upon diet and gene interactions. To investigate the interaction of tomato or lycopene feeding with β-carotene-9',10'-monooxygenase (Bco2) on hepatic metabolic and signaling pathways, male wild-type (WT) and Bco2(-/-) mice (3-wk-old; n = 36) were fed semi-purified control, 10% tomato powder-containing, or 0.25% lycopene beadlet-containing diets for 3 wk. Serum lycopene concentrations were higher in lycopene- and tomato-fed Bco2(-/-) mice compared with WT (P = 0.03). Tomato- and lycopene-fed mice had detectable hepatic apo-6'-, apo-8'-, and apo-12'-lycopenal concentrations. Hepatic expression of β-carotene-15,15'-monooxygenase was increased in Bco2(-/-) mice compared with WT (P = 0.02), but not affected by diet. Evaluation of hepatic gene expression by focused quantitative reverse transcriptase-polymerase chain reaction arrays for nuclear receptors and coregulators (84 genes) and stress and metabolism (82 genes) genes indicates that tomato feeding affected 31 genes (≥1.5-fold, P < 0.05) and lycopene feeding affected 19 genes, 16 of which were affected by both diets. Lycopene down-regulation of 7 nuclear receptors and coregulators, estrogen-related receptor-α, histone deacetylase 3, nuclear receptor coactivator 4, RevErbA-β, glucocorticoid receptor, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ, coactivator 1 β was dependent upon interaction with Bco2 status. Lycopene and tomato feeding induced gene expression patterns consistent with decreased lipid uptake, decreased cell proliferation and mitosis, down-regulated aryl hydrocarbon receptor signaling, and decreased expression of genes involved in retinoid X receptor heterodimer activation. Tomato feeding also caused expression changes consistent with down-regulation of DNA synthesis and terpenoid metabolism. These data suggest tomato components, particularly lycopene, affect hepatic gene expression, potentially affecting hepatic responses to metabolic, infectious, or chemical stress.
Journal of Nutrition 02/2014; 144(10). DOI:10.3945/jn.113.186676 · 3.88 Impact Factor
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