title: SOCS-3 antagonizes pro-apoptotic effects of TRAIL and resveratrol in prostate cancer cells.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Manuela
authors.initials: M
authors.lastname: Horndasch
authors.forename: Zoran
authors.initials: Z
authors.lastname: Culig
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C106644:SOCS3 protein, human; D013267:Stilbenes; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; D000077185:Resveratrol