Low-lycopene containing tomato powder diet does not protect against prostate cancer in TRAMP mice

Conlon, Lauren E.; Wallig, Matthew A.; Erdman, John W.

doi:10.1016/j.nutres.2015.07.003

Cited by 20 publications

(14 citation statements)

References 32 publications

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“…The lack of significant difference in tumor cell proliferation between groups is consistent with results seen in the dorsal and ventral prostate lobes of 10-, 16-, and 24-week-old TRAMP mice [32], and tumor between low-lycopene diets at 12, 16, and 20 weeks of age in C57BL/6 TRAMP x FVB mice [24], but not consistent with the significant decrease in tumor of 17-, 24-, and 36-week-old C57BL/6 TRAMP mice with age [33]. All mice expressed Ki-67 in predominantly PD tumors, which is greater than ~70% of C57BL/6 TRAMP x FVB mice that expressed Ki-67 in PD tumors in a previous study [20].…”

Section: Discussionsupporting

confidence: 84%

“…Given that this study was conducted at the same time using littermates of that study, this outcome was surprising. Overall GU weights, development and progression of prostate cancer were similar to that reported previously [20,22,24], but contrary to another reported previously [19]. We observed a notable increase in iliac lymph node metastases incidence with increasing age.…”

Section: Discussionsupporting

confidence: 77%

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5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores

et al. 2017

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BackgroundThe contribution of 5α-reductase 1 and 5α-reductase 2 to prostate cancer development and progression is not clearly understood. TRAMP mice are a common prostate cancer model, in which 5α-reductase 1 and 5α-reductase 2 expression levels, along with prostate lesions scores, have not been investigated at different time points to further understand prostate carcinogenesis.Method/Principal findingsTo this end, 8-, 12-, 16-, and 20-week-old male C57BL/6TRAMP x FVB mice prostate most severe and most common lesion scores, 5α-reductase 1 and 5α-reductase 2 in situ hybridization expression, and Ki-67, androgen receptor, and apoptosis immunohistochemistry levels were measured. Levels of these markers were quantified in prostate epithelium, hyperplasia, and tumors sections. Mice developed low- to high-grade prostatic intraepithelial neoplasia at 8 weeks as the most severe and most common lesions, and moderate- and high-grade prostatic intraepithelial neoplasia at 12 and 16 weeks as the most severe lesion in all lobes. Moderately differentiated adenocarcinoma was observed at 20 weeks in all lobes. Poorly differentiated carcinoma was not observed in any lobe until 12-weeks-old. 5α-reductase 1 and 5α-reductase 2 were not significantly decreased in tumors compared to prostate epithelium and hyperplasia in all groups, while proliferation, apoptosis, and androgen receptor were either notably or significantly decreased in tumors compared with prostate epithelium and hyperplasia in most or all groups. Prostate 5αR1 levels were positively correlated with adjusted prostate most severe lesion scores.ConclusionDownregulation of androgen receptor and 5α-reductase 2, along with upregulation of 5α-reductase 1 in tumors may promote prostatic intraepithelial neoplasia and prostate cancer development in TRAMP mice.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 77%

5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores

et al. 2017

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“…To date, we are aware of nine publications in models of de novo prostate carcinogenesis (9–15, 23, 58). In the NMU/androgen-induced model of rat prostate carcinogenesis, feeding of tomato powder emerged as more effective in the inhibition of cancer risk than lycopene, which was modestly effective (10).…”

Section: Discussionmentioning

confidence: 99%

“…The concept of greater bioactivity of tomato products compared to lycopene is generally supported by studies in transplantable models using cell lines (22). There are three publications (13, 14, 58) in TRAMP evaluating lycopene at various dosages and durations, with significant inhibition of prostate cancer reported among those studies providing higher lycopene concentrations. One previous study showed that tomato powder reduced TRAMP carcinogenesis, which was potentiated by additional soy intake (48).…”

Section: Discussionmentioning

confidence: 99%

“…Detailed analysis of the pathological grading from the current study (Table 2, Supplemental Figure 3) indicates that dietary tomato and lycopene reduced lesion severity and overall incidence in TRAMP mice, which aligns with recent findings from a 15 study meta-analysis indicating that greater blood lycopene concentrations, resulting from dietary intake of lycopene-containing foods, are inversely correlated with severity and lethality (5). Overall, studies of cancer prevention in rodent models (9–15, 23, 58) provide substantial support for the epidemiologic associations between tomato components and reduced risk of prostate cancer; nonetheless, one should remain cognizant of the potential for publication bias.…”

Section: Discussionmentioning

confidence: 99%

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β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Tan

Thomas‐Ahner

Moran

et al. 2017

Cancer Prevention Research

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The hypothesis that dietary tomato consumption or the intake of the carotenoid lycopene inhibits prostate cancer arose from epidemiologic studies and is supported by preclinical rodent experiments and in vitro mechanistic studies. We hypothesize that variation in activity of carotenoid cleavage enzymes, such as β-carotene 9’,10’-oxygenase (BCO2), may alter the impact of dietary tomato and lycopene on prostate carcinogenesis and therefore examined this relationship in the TRAMP model. Starting at three weeks of age, TRAMP:Bco2+/+ and TRAMP:Bco2−/− mice were fed either AIN-93G control, or semi-purified diets containing 10% tomato powder or 0.25% lycopene beadlets until 18 weeks of age. Both tomato- and lycopene-fed TRAMP:Bco2−/− mice had significantly greater serum concentrations of total, 5-cis, other cis, and all-trans lycopene than TRAMP:Bco2+/+ mice. Tomato- and lycopene-fed mice had a lower incidence of prostate cancer compared to the control-fed mice. While Bco2 genotype alone did not significantly change prostate cancer outcome in the control AIN-93G-fed mice, the abilities of lycopene and tomato feeding to inhibit prostate carcinogenesis were significantly attenuated by the loss of Bco2 (interaction p=0.0004 and p=0.0383, respectively). Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a Bco2 genotype-specific manner, potentially implicating the anticancer activity of lycopene cleavage products. This study suggests that genetic variables impacting carotenoid metabolism and accumulation can impact anti-cancer activity and that future efforts devoted to understanding the interface between tomato carotenoid intake, host genetics, and metabolism will be necessary to clearly elucidate their interactive roles in human prostate carcinogenesis.

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Potential inhibitory effect of lycopene on prostate cancer

Mirahmadi

Azimi-Hashemi

Saburi

et al. 2020

Biomedicine & Pharmacotherapy

124

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Low-lycopene containing tomato powder diet does not protect against prostate cancer in TRAMP mice

Cited by 20 publications

References 32 publications

5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores

5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Potential inhibitory effect of lycopene on prostate cancer

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