Antiproliferative Effects of Ellagic Acid on DU145 Cells

Prostate Cancer (PC) represents a leading cause of tumor-related death among men in the Western world. Above all, DU145 cell line represents the most particular cells model of PC, derived from a central nervous system metastasis. In recent years, functional and healthy diet has gained a pivotal role in society, allowing the possibility to deal with cancer before its emergence or progression, profiting by anti-tumor properties of dietary phytochemicals. Among them, Ellagic Acid (EA) is found in several fruits and vegetables, whose juice demonstrated antioxidant, anti-carcinogenic and anti-fibrotic properties.

DU145 prostate cancer cell line was used to determine the effects of ellagic acid on cell viability. In order to evaluate metastatic feature of DU145, VEGF-A and OPG levels by ELISA assay were assessed. Expression of β-catenin, HO-1, HO-2 and SIRT1, markers of proliferative and defense capacities, were determined by western blotting. To strengthen the study, cell transfection with siRNA β-catenin was performed.

In the presence of EA, the viability of DU145 cells was reduced by about 40 and 50%, respectively after the exposure to 50 and 100 μM concentrations. We also observed a reduction of both levels of VEGF-A and OPG, confirming the important role of EA in facing the metastasis development. EA treatment (50 μM) induced a significant reduction of β-catenin and SIRT1 levels and, similarly, there was a decrease of HO protein expression, more pronounced for HO-2, showing EA activity on the proliferative feature of DU145 cells. Knockdown of β-catenin by siRNA, in the presence of EA treatment, inhibited cell proliferation.

Ellagic acid exhibits significant antiproliferative effects in our in vitro model of prostate cancer’s metastasis, suggesting that, the use of EA as a multitarget natural compound, may represent a possible strategy for cancer chemoprevention.