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SOCS‐3 antagonizes pro‐apoptotic effects of TRAIL and resveratrol in prostate cancer cells
Author(s) -
Horndasch Manuela,
Culig Zoran
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21353
Subject(s) - du145 , lncap , prostate cancer , apoptosis , propidium iodide , cancer research , programmed cell death , resveratrol , cytokine , tumor necrosis factor alpha , receptor , cancer , biology , medicine , immunology , pharmacology , biochemistry
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. Prostate 71:1357–1366, 2011. © 2011 Wiley‐Liss, Inc.