The resistance of esophageal adenocarcinoma to bile salt insult is associated with manganese superoxide dismutase expression.
BACKGROUND
Bile acids are implicated as etiologic agents in esophageal cancer. We sought to analyze the impact of bile acid exposure on esophageal epithelial cells, Barrett's metaplastic cells (BE), esophageal adenocarcinoma cells (EAC), and esophageal squamous carcinoma cell (ESC). We sought to determine if cellular resistance is related to manganese superoxide dismutase expression.


METHODS
Cells were exposed to sodium choleate (CA), sodium deoxycholate (DCA), sodium glycocholate (GCA), sodium taurocholate (TCA), or a 1:1 mixture (MIX) of reagents at concentrations in the range 0.2-0.8 mM. Cell viability was evaluated by MTT assay. Manganese superoxide dismutase (MnSOD) expression was analyzed by Western blot. Statistical analysis was performed using SPSS ver. 17.0, SPSS Inc., Chicago, IL.


RESULTS
Bile salt exposure inhibited cell viability in esophageal squamous cells in time- and growth-dependent manner. There was a 50% decrease in cell viability from 4 to 24 h. BE, EAC, and ESC cell lines were more resistant to bile insult. In untreated cell lines, MnSOD expression was significantly decreased in EAC and ESC cell lines compared with esophageal squamous epithelial cells and BE cells (P=0.002). Exposure of ESC cells to bile salt increased MnSOD expression.


CONCLUSIONS
The confirmation of the role of reactive oxygen species (ROS) and bile acids in esophageal carcinogenesis has interesting implications for chemoprevention in patients with reflux esophagitis and Barrett's esophagus. Further studies are necessary to assess the preventative role of antioxidant supplementation.
Schiffman
Suzanne C
SC
Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, Kentucky 40202, USA.
Li
Yan
Y
Xiao
Deyi
D
Li
Xuanshe
X
Aiyer
Harini S
HS
Martin
Robert C G
RC
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000975:Antioxidants / Q000378:metabolism; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D001647:Bile Acids and Salts / Q000378:metabolism* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*
D000975:Antioxidants; D001647:Bile Acids and Salts; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase