Abstract 1999: Specific pomegranate juice components are potential inhibitors of prostate cancer metastasis

Introduction: Prostate cancer is the second-leading cause of cancer-related mortality in U.S men. 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. Recently, Pomegranate juice (PJ) has been identified as a natural product that inhibits prostate cancer progression. In an UCLA phase II clinical trial, patients with rising PSA were given 8 oz of PJ by mouth daily. PSA doubling time significantly increased with treatment from a mean of 15 months to 54 months post-treatment. We have shown previously that PJ inhibits the migratory and metastatic properties of prostate cancer cells by stimulating cell adhesion and inhibiting cell migration and chemotaxis. However, the soluble phase of PJ contains many components and as a whole it is difficult to determine how to best maximize its use in treating prostate cancer. A way to overcome this challenge is to identify chemical components of PJ responsible for the anti-metastatic effect of whole juice. Methods: By using two hormone-independent prostate cancer cell lines PC3 and DU145 and one hormone-sensitive cell line LNCaP, we took an integrative approach using Affymetrix gene arrays and miRNA PCR arrays to identify specific PJ components that have similar effects as the juice on cell adhesion, migration and chemotaxis. Results: We show that the specific PJ components luteolin, ellagic acid and punicic acid individually inhibit growth of hormone-dependent and -independent prostate cancer cells, and also inhibit their migration and their chemotaxis towards SDF1α, a factor that is important in prostate cancer metastasis to the bone. However, the greatest effects were observed when the three components were used together. In addition, our Affymetrix gene array results show that these components also increase the expression of cell adhesion genes and decrease expression of genes involved in cell cycle control and cell migration. Moreover, miRNA PCR array results show that these components increase several well-known tumor-suppressive miRNAs and decrease several oncogenic miRNAs. We also show that these components inhibit the CXCR4/SDF1α chemotaxis axis. Moreover, when taken together, the integrated results of the gene and miRNA arrays show a powerful correlation in regulation of function by the specific genes important in processes critical for metastasis. Conclusion: Our results suggest that these components may be a more effective inhibitor of prostate cancer metastasis than the whole juice. Chemical modification of these compounds could further enhance their bioavailability and efficacy of treatment. Moreover, because the mechanisms of metastasis are similar for most cancers, these PJ components may also be effective in treatment of metastasis of other cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1999. doi:1538-7445.AM2012-1999