Dietary tomato or lycopene do not reduce castration-resistant prostate cancer progression in a murine model

Authors: ROWLES III, JOE - University Of Illinois; SMITH, JOSHUA - University Of Illinois; APPLEGATE, CATHERINE - University Of Illinois; MILLER, RITA - University Of Illinois; WALLIG, MATTHEW - University Of Illinois; KAUR, AMANDEEP - University Of Illinois; SAROL JR, JESUS - University Of Illinois; MUSAAD, SALMA - Children'S Nutrition Research Center (CNRC); CLINTON, STEVEN - The Ohio State University; O'BRIEN JR, WILLIAM - University Of Illinois; ERDMAN JR, JOHN - University Of Illinois

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/26/2020
Publication Date: 5/5/2020
Citation: Rowles III, J.L., Smith, J.W., Applegate, C.C., Miller, R.J., Wallig, M.A., Kaur, A., Sarol Jr, J.N., Musaad, S., Clinton, S.K., O'Brien Jr, W.D., Erdman Jr, J.W. 2020. Dietary tomato or lycopene do not reduce castration-resistant prostate cancer progression in a murine model. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa107.
DOI: https://doi.org/10.1093/jn/nxaa107

Interpretive Summary: Prostate cancer is the second leading cause of cancer related deaths among men in the US. Lowering testosterone action is one common way to treat it. However, in some men the cancer keeps growing or comes back after lowering testosterone action. This type of prostate cancer is called castration-resistant prostate cancer (CRPC). Dietary tomato products protect against prostate cancer in general, but their effect on CRPC is unknown. To test whether dietary tomato products will reduce the CRPC, mice were first castrated then either fed a tomato diet reaching levels found in human blood or fed a regular diet. The development of CRPC did not differ among the mice. These results suggest that, as men with prostate cancer begin testosterone lowering therapy, they should focus on fitness and other healthy dietary guidelines rather than tomato supplements.

Technical Abstract: Dietary tomato products or lycopene protect against prostate carcinogenesis, but their impact on the emergence of castration-resistant prostate cancer (CRPC) is unknown. We hypothesized that tomato or lycopene products would reduce the emergence of CRPC. Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were castrated at 12-13 wk and the emergence of CRPC was monitored by ultrasound in each study. In Study 1, TRAMP mice (n=80) were weaned onto an AIN-93G-based control diet (Con-L, n=28), a 10% tomato powder diet (TP-L, 10% lyophilized w/w, n=26), or a control diet followed by a tomato powder diet after castration (TP-Int1, n=26). In Study 2, TRAMP mice (n=85) were randomized onto a control diet with placebo beadlets (Con-Int, n=29), a tomato diet with placebo beadlets (TP-Int2, n=29), or a control diet with lycopene beadlets (Lyc-Int, n=27) following castration (aged 12 wk). Tumor incidence and growth were monitored by ultrasound beginning at an age of 10 wk. Mice were euthanized 4 wk after tumor detection or aged 30 wk if no tumor was detected. Tissue weights were compared by ANOVA followed by Dunnett's test. Tumor volumes were compared using generalized linear mixed model regression. Ultrasound estimates for the in vivo tumor volume were strongly correlated with tumor weight at necropsy (R2=0.75 and 0.94, P<0.001 for both Studies 1 and 2, respectively). Dietary treatments after castration did not significantly impact cancer incidence, time to tumor detection, or final tumor weight. In contrast to studies of de novo carcinogenesis in multiple preclinical models, tomato components had no significant impact on the emergence of CRPC in the TRAMP model. It is possible that specific mutant subclones of prostate cancer may continue to show some antiproliferative response to tomato components, but further studies are needed to confirm this.