Abstract 4327: Dietary tomato reduces castration-resistant prostate cancer progression in TRAMP mice

Abstract

Abstract Epidemiological data support the hypothesis that consumption of diets rich in tomato products are associated with a reduced risk of prostate cancer. Castration-resistant prostate cancer (CRPC) represents the late and lethal phase of human prostate carcinogenesis, and is defined as cancer progression after surgical castration or pharmacologic reduction of serum testosterone through androgen deprivation therapy. Mechanisms involved in the transition to CRPC include cancer cells’ acquired capacity for androgen synthesis or activation of ligand-independent signaling. We have previously shown that dietary tomato can inhibit prostatic androgen signaling and expression of androgen biosynthetic genes, as well as reduce primary cancer incidence in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Therefore, we examined whether dietary tomato might be an effective inhibitor of CRPC progression in mice. We hypothesized that lifelong dietary intake of tomato, as well as dietary tomato intervention following castration, would reduce tumor burden and growth rate in a mouse model of CRPC. TRAMP mice were fed an AIN-93G diet (CON) for one week and then randomized to the CON diet (n = 28) or a similar diet with 10% w/w lyophilized tomato paste (TP; n = 27) from 4 wks of age until euthanization. A third group, modeling dietary intervention, consumed CON from 4 to 12 wks of age, and the 10% w/w lyophilized tomato paste diet from wk 12 until euthanization (TP-I; n = 25). All animals were castrated at 12 wks of age. Beginning at 10 wks of age, mice were monitored longitudinally with ultrasound for tumor detection, tumor volume estimation, and calculation of tumor growth rate. Serial 2D image slices were used to generate a 3D volume estimate. Mice were euthanized after 5 consecutive tumor scans, or if no tumor had been detected by 30 weeks of age. Tumor growth area under the curve (AUC) was reduced approximately 46% by tomato intervention (TP-I) and 27% by lifelong tomato consumption (TP). At euthanization, TP-I reduced tumor weight by approximately 26%. Additionally, incidence of gross metastases to distant organs (lung, liver, kidney) was strongly inhibited by TP-I, compared to CON (0% and 26%, respectively). TP diet reduced incidence of distant organ gross metastasis to <10%. The consumption of tomato products following castration inhibits CRPC progression in the TRAMP model. Our findings support the development of human studies of dietary tomato interventions in combination with anti-androgen therapy for men with advanced prostate cancer. Citation Format: Joshua W. Smith, Joe L. Rowles, Rita J. Miller, Steven K. Clinton, William D. O’Brien, John W. Erdman. Dietary tomato reduces castration-resistant prostate cancer progression in TRAMP mice. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4327.