Curcumin and anthocyanin inhibit pepsin-mediated cell damage and carcinogenic changes in airway epithelial cells. Ann Otol Rhinol Laryngol 2013 Oct;122(10):632-41
Date
12/04/2013Pubmed ID
24294686DOI
10.1177/000348941312201006Scopus ID
2-s2.0-84887079765 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
OBJECTIVES: 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.
Author List
Samuels TL, Pearson AC, Wells CW, Stoner GD, Johnston NAuthor
Nikki Johnston PhD Professor in the Otolaryngology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnthocyaninsAnti-Inflammatory Agents, Non-Steroidal
Cell Proliferation
Curcumin
DNA Damage
Drug Therapy, Combination
Epithelial Cells
Gene Expression Regulation
Genes, Tumor Suppressor
Head and Neck Neoplasms
Humans
Immunohistochemistry
Laryngopharyngeal Reflux
Microscopy, Electron, Transmission
Mitochondria
Pepsin A
Phytochemicals
