title: Heat shock protein 27 expression in areca quid chewing-associated oral squamous cell carcinomas.
abstract: OBJECTIVE
  Heat shock protein (HSP) 27 is a low-molecular-weight protein that functions as a molecular chaperone and plays a cytoprotective role through its antioxidant activity during cell stress. Areca quid chewing is associated with the high incidence of oral squamous cell carcinomas (OSCCs) in Taiwan. The aim of this study was to compare heat shock protein 27 (HSP27) expression in OSCCs and the normal oral tissues.
  
  
  METHODS
  Forty-eight OSCCs from areca quid chewers and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry for HSP27. The normal human oral keratinocytes (HOKs) were challenged with arecoline, the major alkaloid of areca nut, by Western blot for HSP27. Furthermore, epigallocatechin-3 gallate (EGCG), glutathione precursor N-acetyl-L-cysteine (NAC), cyclooxygenase-2 inhibitor NS-398, HSP inhibitor quercetin, extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, and p38 inhibitor SB203580 were added to find the possible regulatory mechanisms.
  
  
  RESULTS
  Heat shock protein 27 exhibited higher expression in OSCCs than normal specimens (P < 0.05). Arecoline was found to elevate HSP27 expression in a dose- and time-dependent manner (P < 0.05). The additions of pharmacological agents were found to inhibit arecoline-induced HSP27 expression (P < 0.05).
  
  
  CONCLUSIONS
  Heat shock protein 27 expression is significantly elevated in areca quid chewing-associated OSCCs. Arecoline-induced HSP27 expression was downregulated by EGCG, NS398, NAC, quercetin, PD98059, and SB203580.
authors.affiliation: School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: S-S
authors.initials: SS
authors.lastname: Lee
authors.forename: C-H
authors.initials: CH
authors.lastname: Tsai
authors.forename: Y-C
authors.initials: YC
authors.lastname: Ho
authors.forename: C-C
authors.initials: CC
authors.lastname: Yu
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D001114:Areca / Q000009:adverse effects*; D001115:Arecoline / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism*; D016022:Case-Control Studies; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005419:Flavonoids; D055551:HSP27 Heat-Shock Proteins; D007093:Imidazoles; D009578:Nitrobenzenes; D011725:Pyridines; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D001115:Arecoline; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000111:Acetylcysteine