title: Combined valproic acid and celecoxib treatment induced synergistic cytotoxicity and apoptosis in neuroblastoma cells.
abstract: BACKGROUND
  The effects of combined valproic acid (VPA) and celecoxib treatment on cancer cells have not been reported. In this study, we examined the effects of VPA and celecoxib, alone and combined, on human SH-SY5Y neuroblastoma cells.
  
  
  METHODS
  The cytotoxicity effects of VPA, celecoxib, and combined VPA and celecoxib treatment on neuroblastoma cells were studied. The apoptotic fraction and the cell cycle distribution of neuroblastoma cells were analyzed by flow-activated cell sorter analysis. Western blot analysis was used to investigate the expression of cyclooxygenase-2, p53, 14-3-3σ, p21, p27, Bcl-2 and Bax in neuroblastoma cells treated with various regimens.
  
  
  RESULTS
  Combined VPA and celecoxib treatment caused more cytotoxicity and apoptosis in neuroblastoma cells than individual drug treatment (p<0.05). In addition, combination treatment caused more neuroblastoma cells to accumulate in the G0/G1 phase of the cell cycle (p<0.04) and induced higher p21 and p27 expression than individual drug treatment or control.
  
  
  CONCLUSIONS
  Combined VPA and celecoxib treatment induced more cytotoxicity and apoptosis in neuroblastoma cells than individual drug treatment. The effects were probably related to the increased p21 and p27 expression, and G0/G1 accumulation of neuroblastoma cells.
authors: Department of Surgery, Far Eastern Memorial Hospital, New Taipei, Taiwan, ROC.
authors: Yun
authors: Y
authors: Chen
authors: Ya-Hui
authors: YH
authors: Tsai
authors: Sheng-Hong
authors: SH
authors: Tseng
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D004357:Drug Synergism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011720:Pyrazoles; D013449:Sulfonamides; D050760:Cyclin-Dependent Kinase Inhibitor p27; D014635:Valproic Acid; D000068579:Celecoxib