Abstract 963: Bioactive tomato components antagonize the androgen regulation of epithelial cell turnover in the mouse prostate

Abstract

Abstract Introduction: Testosterone is a critical regulator of prostate function and carcinogenesis. Inhibition of testosterone action is an approach for prostate cancer prevention. We hypothesize that consumption of tomato phytochemicals may have a protective impact during prostate carcinogenesis via inhibition of androgen signaling in the prostate epithelium. Methods: Four week-old C57/BL6 male mice (n=84) were fed either: AIN93-G diet as a control, AIN93-G with10% tomato powder (0.02 g LYC/Kg diet) or AIN93-G with 10% LYC beadlets (0.40 g LYC/Kg diet). At eight weeks of age, mice were randomized among three endocrine treatments: intact control, castration, or castration + testosterone repletion (2.5 mg testosterone propionate/Kg body weight/mouse/day by subcutaneous osmotic minipumps starting 7 days after castration). At 10 weeks of age, blood was collected for carotenoid analysis by HPLC and tissues were collected for evaluating prostate epithelial cell proliferation index (Ki67), apoptosis index (ApopTag), and other biomarkers. Results: Dietary intakes did not differ among groups. However, the estimated LYC consumption was 0.00 mg/d for controls, 1.13 mg/d in LYC fed mice, and 0.06 mg/d in tomato fed mice (P< 0.001). Interestingly, serum LYC levels did not differ between mice fed the tomato and LYC diets (366 and 371 nmol/L, respectively). As anticipated, castration decreased proliferative indices in control mice (1.8% vs. 4.7%) and testosterone repletion restored and further enhanced the proliferative index (15.8%) (P<0.02). Compared to mice fed the control diet, tomato and LYC fed mice had significantly reduced prostate epithelial proliferation index in the intact mice by approximately 50% (P<0.02) and testosterone treated mice by over 30% (P<0.001), whereas no dietary impact was observed in castrated mice. Castration enhanced the apoptotic index compared to controls (1.7% vs. 0.8%) while testosterone repletion reversed the effect of castration (0.7% vs. 1.7%). Mice fed the tomato diet, showed enhanced castration induced apoptosis compared to those fed the LYC or control diet (P<0.05). Similar trends were observed in the apoptotic index in LYC fed mice but without reaching significance. Conclusion: LYC absorption in mice is limited and similar blood concentrations are achieved over a wide range of dietary intake from either pure LYC or tomato components. Mice consuming tomato powder or LYC show reduced prostate epithelial proliferation in response to testosterone. Tomato powder is a more potent enhancer of apoptotic cascades in response to androgen deprivation. Bioactive components in tomatoes in addition to LYC may influence prostate biology and participate in the inhibition of prostate carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 963.