SOCS-3 antagonizes pro-apoptotic effects of TRAIL and resveratrol in prostate cancer cells.

Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
Therapy for advanced prostate cancer is only palliative and its improvement could be achieved by sensitization to pro-apoptotic agents to which resveratrol belongs. We investigated the interaction between the tumor-selective apoptosis inducer tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and suppressor of cytokine signaling (SOCS-3), an antiapoptotic molecule which is up-regulated in prostate cancer.Expression of SOCS-3 and TRAIL (death) receptors was determined by Western blot after treatment with TRAIL in prostate cancer cell lines. Binding of SOCS-3 to death receptors was investigated by immunoprecipitation. Apoptosis rate was determined by a propidium iodide assay after treatment by TRAIL and resveratrol.SOCS-3, whose expression was differentially regulated by TRAIL in androgen-insensitive prostate cell lines, binds to death receptor 4. Overexpression of SOCS-3 reduced apoptosis in TRAIL- and resveratrol-treated DU145 cells and SOCS-3 siRNA increased apoptosis in TRAIL-treated PC-3 and LNCaP-IL-6+ cells.Our results strongly suggest that SOCS-3 is one of the proteins which influence the ability of TRAIL and resveratrol to cause programmed cell death in prostate cancer.
Mesh Terms:
Antineoplastic Agents, Phytogenic, Apoptosis, Cell Line, Tumor, Down-Regulation, Humans, Male, Prostatic Neoplasms, RNA, Small Interfering, Receptors, TNF-Related Apoptosis-Inducing Ligand, Stilbenes, Suppressor of Cytokine Signaling Proteins, TNF-Related Apoptosis-Inducing Ligand, Up-Regulation
Prostate Sep. 01, 2011; 71(12);1357-66 [PUBMED:21308719]
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