Novel Resveratrol Derivatives Induce Apoptosis and Cause Cell Cycle Arrest in Prostate Cancer Cell Lines

Background: Resveratrol (RV), a naturally occurring phytoalexin, exerts manifold biological effects against a variety of human tumor cell lines. In this study, the cytotoxic and biological effects of novel RV derivatives were investigated in prostate cancer cells. Materials and Methods: Cytotoxicity of the compounds was assessed by clonogenic assays in PC-3, LNCaP and DU-145 human prostate cancer cell lines. Induction of apoptosis was studied by Hoechst-propidium-iodide double staining. Cell cycle phase distribution of prostate cancer cells was analyzed using flow cytometry. Results: Methoxy- and hydroxy-substituted RV derivatives exerted cytotoxic effects against all three cell lines. The most potent compounds, 3,3′,4,4′,5,5′-hexahydroxy-stilbene and 3,4,4′,5-tetramethoxy-stilbene, induced apoptosis at concentrations lower than RV and caused cell cycle arrest in the cell lines investigated. Conclusion: Introducing additional hydroxy- and methoxy-moieties to the stilbene ring of RV is capable of enhancing its cytotoxic and pro-apoptotic effects in hormone-responsive and non-responsive prostate cancer cells.