RESEARCH ARTICLE


Antiproliferative Effects of Ellagic Acid on DU145 Cells



Giuseppe Carota, Giuseppe Sferrazzo, Mariarita Spampinato, Valeria Sorrenti, Luca Vanella*
Department of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125, Catania, Italy


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© 2019 Carota et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Drug Science, Biochemistry Section, University of Catania, Viale A. Doria 6, 95125 Catania, Italy; Tel: 0957384077; E-mail: lvanella@unict.it


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 defense capacities, 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 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.

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.

Keywords: Antiproliferative, Prostate cancer, Metastasis, DU145e, VEGF-A, OPG.