Ellagic Acid: Cytodifferentiating and Antiproliferative Effects In Human Prostatic Cancer Cell Lines

Background: Recently, increasing attention has been given to neuroendocrine differentiation (NED) of Prostate Cancer and its diagnostic, prognostic and therapeutic potential. During multistep carcinogenesis, cytodifferentiation of malignant/premalignant cells into more mature or normal-like cells, has become an attractive modality of treatment and promises to be a less toxic and a more specific targeting strategy than conventional chemotherapy. In this study we investigated the capacity of a polyphenol, ellagic acid (EA), to induce differentiation of two prostate cancer cell lines: LnCap and DU145. Methods: NED markers, Chromogranin A (CgA) and p75NGFR levels were evaluated by immunocytochemistry. DNA methyltransferase- 1 (DNMT-1) and phospho-Rb (p-Rb) expression were evaluated by western blotting. Akt activation was evaluated by ELISA. Finally the ability of EA to induce DNA damage in cancer cells was examined using the COMET assay. Results: Treatment with EA significantly reduced CgA levels and increased p75NGFR expression. Moreover p-Rb, DNMT-1 levels and Akt activation/phosphorylation were decreased. EA treatment induced, in a dose-dependent manner, a marked increase in DNA damage, both in LnCap and DU145 cell lines. Conclusions: The results of this study demonstrate that EA treatment represents a new approach and highly effective strategy in reducing carcinogenesis. Therefore, EA may be considered in a promising new class of cancer therapeutic agent, with both antiproliferative and pro-differentiation properties.