Abstract 2244: Pomegranate juice components as novel treatment for prostate cancer metastasis.

Abstract

Abstract Introduction: Prostate cancer is the second cause of cancer deaths in men in the United States. To date there is no real cure for the disease beyond surgery and/or radiation. Early stages can be controlled with hormone ablation therapy that suppresses the rate of prostate cancer growth. However, over time, the cancer overcomes its hormone dependence, becomes highly aggressive and metastasizes to the lymph nodes and bone marrow. Pomegranate juice (PJ) is a natural product that inhibits prostate cancer progression. A clinical trial in which patients with recurrent prostate cancer were given 8 oz of PJ by mouth daily resulted in none of the patients progressing to a metastatic stage during the period of the trial. We have previously shown that the PJ components luteolin (L), ellagic acid (E) and punicic acid (P) together inhibit growth of hormone-dependent and -independent prostate cancer cells, their migration and their chemotaxis towards SDF1α, a factor that is important in prostate cancer metastasis to the bone. However, the in vivo effectiveness of these components needs to be determined. Methods: To study the effect of L+E+P in vivo, we used the SCID (Severely Combined Immuno-Deficiency) mouse model in which luciferase expressing prostate cancer cells were injected ectopically. Tumor progression was monitored with Bioluminescence Imaging (BLI) weekly. To study the effect of L+E+P on angiogenesis, we performed a variety of cell and molecular assays using human endothelial cells (HMEC) in culture. Results: We found that L+E+P significantly inhibited PC3-luc2 primary tumor growth and angiogenesis and that none of the tumors treated with L+E+P metastasized. We also found that L+E+P significantly inhibited the SDF1α/CXCR4 axis this mouse model which is consistent with our in vitro findings. In addition, the tube formation assay with HMEC showed that L+E+P not only prevented tube formation but also disrupted pre-formed tubes. The activation of AKT and VEGF receptor 2 (VEGFR2) by IL-8, a potent pro-angiogenesis chemokines, was inhibited by L+E+P. Conclusion: Our results suggest that the L+E+P components of PJ can potentially be developed as a novel treatment to inhibit prostate cancer metastasis. These components may be more effective in inhibiting of prostate cancer metastasis than simply drinking the juice. Chemical modification of these may further enhance their bioavailability and efficacy of treatment. Moreover, because the mechanisms of metastasis are similar for most cancers, these PJ components L+E+P may also be effective in treatment of metastasis of other cancers. Citation Format: Lei Wang, Wen Fang Li, David Mulholland, Manuela Martins-Green. Pomegranate juice components as novel treatment for prostate cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2244. doi:10.1158/1538-7445.AM2013-2244