title: Endoplasmic reticulum stress response as a possible mechanism of cyclooxygenase-2-independent anticancer effect of celecoxib.
abstract: BACKGROUND
  We investigated whether the endoplasmic reticulum (ER) stress response could be a cyclooxygenase-2 (COX2)-independent mechanism of growth inhibition by celecoxib in a head and neck squamous cell carcinoma (HNSCC) cell line.
  
  
  METHODS
  We performed western blotting and reverse transcription polymerase chain reaction to analyze the expression of ER stress response-associated proteins C/EBP homologous protein (CHOP), glucose-regulated protein (GRP)-78 and X-box binding protein-1 (XBP1), after treatment of celecoxib in the SNU-1041 cell line. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the change in growth inhibition by celecoxib after inhibition of the ER stress pathway by CHOP small-interfering RNA (siRNA).
  
  
  RESULTS
  Celecoxib triggered an ER stress response in this HNSCC cell line as shown by activation of CHOP, GRP78 and XBP1. The inhibition of cell proliferation by celecoxib was effectively hindered with CHOP siRNA.
  
  
  CONCLUSIONS
  ER stress response could be a COX2-independent anticancer mechanism of celecoxib.
authors.affiliation: Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul 110-744, Korea. jhunhah@snu.ac.kr.
authors.forename: Wonjae
authors.initials: W
authors.lastname: Cha
authors.forename: Seok-Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Tack-Kyun
authors.initials: TK
authors.lastname: Kwon
authors.forename: J Hun
authors.initials: JH
authors.lastname: Hah
authors.forename: Myung-Whun
authors.initials: MW
authors.lastname: Sung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011720:Pyrazoles / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D011720:Pyrazoles; D013449:Sulfonamides; D051742:Transcription Factor CHOP; D051546:Cyclooxygenase 2; D000068579:Celecoxib
keywords: COX2; Celecoxib; endoplasmic reticulum stress response; head and neck cancer