Antiproliferative Effects of Ellagic Acid on DU145 Cells

Abstract

Background: 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. Methods: 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 defensecapacities, were determined by western blotting. To strengthen the study, cell transfection with siRNA β-catenin was performed. Results: 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 metastasisdevelopment. 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. Conclusion: 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.