Abstract

Prostate cancer (PCa) remains the second most diagnosed cancer worldwide. Higher body weight is associated with chronic inflammation, increased angiogenesis, and treatment-resistant tumor phenotypes. Dietary tomato reduces PCa risk, which may be due to tomato inhibition of angiogenesis and disruption of androgen signaling. This pilot study investigated the interplay between tomato powder (TP), incorporated into control (CON) and obesogenic (OB) diets, and PCa tumor growth and blood perfusion over time in a transgenic model of PCa (TRAMP). Ultrasound microvessel imaging (UMI) results showed good agreement with gold-standard immunohistochemistry quantification of endothelial cell density, indicating that this technique can be applied to non-invasively monitor tumor blood perfusion in vivo. Greater body weight was positively associated with tumor growth. We also found that TP significantly inhibited prostate tumor angiogenesis but that this inhibition differentially affected measured outcomes depending on CON or OB diets. TP led to reduced tumor growth, intratumoral inflammation, and intratumoral androgen-regulated gene expression (srd5a1, srd5a2) when incorporated with the CON diet but greater tumor growth and intratumoral gene expression when incorporated with the OB diet. Results from this study show that protective benefits from dietary tomato are lost, or may become deleterious, when combined with a Western-style diet.

Highlights

  • Prostate cancer (PCa) remains the second most diagnosed cancer worldwide

  • Carotenoid profiles were similar between tomato powder (TP) and TP-containing diets, and concentrations were similar between control (CON-TP) and obesogenic (OB-TP) diets (Supplementary Fig. S1)

  • A significant interaction was observed whereby TP reduced both srd5a1 (p = 0.030) and srd5a2 (p = 0.016) expression in CON-fed animals and increased srd5a1 and srd5a2 expression in OB-fed animals. This pilot study evaluated the effects of diet-induced obesity and tomato intake on advanced prostate tumor growth and longitudinal measurements of tumor blood perfusion; the latter measured using a novel application and modifications to our previously published high-frequency Ultrasound microvessel imaging (UMI) t­echnique[30]

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Summary

Introduction

Prostate cancer (PCa) remains the second most diagnosed cancer worldwide. Higher body weight is associated with chronic inflammation, increased angiogenesis, and treatment-resistant tumor phenotypes. Dietary tomato reduces PCa risk, which may be due to tomato inhibition of angiogenesis and disruption of androgen signaling This pilot study investigated the interplay between tomato powder (TP), incorporated into control (CON) and obesogenic (OB) diets, and PCa tumor growth and blood perfusion over time in a transgenic model of PCa (TRAMP). Adipose tissue expansion leads to hypoxia, promoting adipocyte crosstalk with vascular stromal cells to stimulate additional angiogenesis, which in turn promotes tumor g­ rowth[16] Despite this evidence and the limited efficacy of some clinical trials testing anti-angiogenic therapies in ­PCa17,18, the majority of phase III trials do not support improvements in overall survival by inhibiting ­angiogenesis[19,20,21,22]. Tomato and lycopene appear to interact with the androgen axis in PCa, disrupting androgen metabolism through downregulation of the androgen receptor (AR) and AR-regulated steroid-metabolizing e­ nzymes[28]

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