SOCS-3 Antagonizes Pro-Apoptotic Effects of TRAIL and Resveratrol in Prostate Cancer Cells

作者：Horndasch Manuela; Culig Zoran^*

来源：Prostate, 2011, 71(12): 1357-1366.

DOI：10.1002/pros.21353

• prostate cancer
• suppressor of cytokine signaling-3
• TRAIL
• resveratrol
• apoptosis

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-11-6+ 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. Prostate 71: 1357-1366, 2011.

• 出版日期2011-9-1