TY - JOUR
T1 - Dietary tomato inhibits angiogenesis in TRAMP prostate cancer but is not protective with a Western-style diet in this pilot study
AU - Applegate, Catherine C.
AU - Lowerison, Matthew R.
AU - Hambley, Emma
AU - Song, Pengfei
AU - Wallig, Matthew A.
AU - Erdman, John W.
N1 - Funding Information:
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 angiogenesis19–22. Epidemiological studies have demonstrated that intake of tomato and its primary bioactive, lycopene, reduce the risk for PCa-specific mortality23,24. Higher dietary intake of lycopene is associated with reduced angiogenesis in PCa tumors23; this epidemiological relationship is supported by mechanistic studies in which lycopene treatments inhibited angiogenesis and angiogenic factors in vitro and in vivo25–27. Furthermore, 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 enzymes28.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-021-97539-2
DO - 10.1038/s41598-021-97539-2
M3 - Article
C2 - 34535690
AN - SCOPUS:85115413657
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 18548
ER -