Specific Pomegranate Juice Components as Potential Inhibitors of Prostate Cancer Metastasis

Abstract

Pomegranate juice (PJ) is a natural product that inhibits prostate cancer progression. A clinical trial on patients with recurrent prostate cancer resulted in none of the patients progressing to a metastatic stage during the period of the trial. We have previously found that, in addition to causing cell death of hormone-refractory prostate cancer cells, PJ also markedly increases adhesion and decreases migration of the cells that do not die. However, because PJ is a very complex mixture of components and is found in many different formulations, it is important to identify specific components that are effective in inhibiting growth and metastasis. Here, we show that the PJ components luteolin, ellagic acid, and punicic acid together inhibit growth of hormone-dependent and hormone-refractory prostate cancer cells and inhibit their migration and their chemotaxis toward stromal cell-derived factor 1α (SDF1α), a chemokine that is important in prostate cancer metastasis to the bone. These components also increase the expression of cell adhesion genes and decrease expression of genes involved in cell cycle control and cell migration. Furthermore, they increase several well-known tumor-suppression microRNAs (miRNAs), decrease several oncogenic miRNAs, and inhibit the chemokines receptor type 4 (CXCR4)/SDF1α chemotaxis axis. Our results suggest that these components may be more effective in inhibiting prostate cancer growth and metastasis than simply drinking the juice. Chemical modification of these components 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 the treatment of metastasis of other cancers.