title: Curcumin and anthocyanin inhibit pepsin-mediated cell damage and carcinogenic changes in airway epithelial cells.
abstract: OBJECTIVE
  Laryngopharyngeal reflux (LPR) is associated with inflammatory and neoplastic airway diseases. Gastric pepsin internalized by airway epithelial cells during reflux contributes to oxidative stress, inflammation, and carcinogenesis. Several plant extracts and compounds inhibit digestive enzymes and inflammatory or neoplastic changes to the esophagus in models of gastroesophageal reflux. This study examined the potential of chemoprotective phytochemicals to inhibit peptic activity and mitigate pepsin-mediated damage of airway epithelial cells.
  
  
  METHODS
  Cultured human laryngeal and hypopharyngeal epithelial cells were pretreated with curcumin (10 micromol/L), ecabet sodium (125 microg/mL), and anthocyanin-enriched black-raspberry extract (100 microg/mL) 30 minutes before treatment with pepsin (0.1 mg/mL; 1 hour; pH 7). Controls were treated with media pH 7 or pepsin pH 7 without phytochemicals. Cell damage and proliferative changes were assessed by electron microscopy, cell count, thymidine analog incorporation, and real-time polymerase chain reaction array. Pepsin inhibition was determined by in vitro kinetic assay.
  
  
  RESULTS
  Micromolar concentrations of curcumin, ecabet sodium, and black-raspberry extract inhibited peptic activity and pepsin-induced mitochondrial damage and hyperproliferation. Curcumin abrogated pepsin-mediated depression of tumor suppressor gene expression and altered the subcellular localization of pepsin following endocytosis.
  
  
  CONCLUSIONS
  Several phytochemicals inhibit the pepsin-mediated cell damage underlying inflammatory or neoplastic manifestations of LPR. Dietary supplementation or adjunctive therapy with phytochemicals may represent novel preventive or therapeutic strategies for LPR-attributed disease.
authors.affiliation: Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Samuels
authors.forename: Amy C S
authors.initials: AC
authors.lastname: Pearson
authors.forename: Clive W
authors.initials: CW
authors.lastname: Wells
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stoner
authors.forename: Nikki
authors.initials: N
authors.lastname: Johnston
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000187:drug effects / Q000502:physiology; D006258:Head and Neck Neoplasms; D006801:Humans; D007150:Immunohistochemistry; D057045:Laryngopharyngeal Reflux / Q000473:pathology / Q000517:prevention & control; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology; D010434:Pepsin A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064209:Phytochemicals / Q000494:pharmacology
chemical_list: D000872:Anthocyanins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D064209:Phytochemicals; D010434:Pepsin A; D003474:Curcumin