title: Alpha linolenic acid and oleic acid additively down-regulate malignant potential and positively cross-regulate AMPK/S6 axis in OE19 and OE33 esophageal cancer cells.
abstract: OBJECTIVE
  Both oleic acid (OA) and alpha-linolenic acid (ALA) have been proposed to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that OA and/or ALA suppresses to the development of esophageal cancer has not been studied. Also, no previous studies have evaluated how OA and/or ALA regulates malignant potential (cell proliferation, migration, colony formation and adhesion) and intracellular signaling pathways, and whether their effects might be synergistic and/or additive in esophageal cancer cells has not yet been elucidated.
  
  
  METHODS
  We conducted in vitro studies and evaluated whether OA and ALA alone or in combination may regulate malignant potential in OE19 and OE33 esophageal cancer cell lines.
  
  
  RESULTS
  Both OA and ALA significantly down-regulated cell proliferation, adhesion and/or migration. OA and/or ALA did not change the number of colonies but decrease colony sizes when compared to control. Also, we observed that OA and/or ALA positively cross-regulates the expression levels of AMPK/S6 axis. Moreover, OA and ALA up-regulated tumor suppressor genes (p53, p21, and p27) and these effects are abolished by AMPK siRNA administration. Importantly, we observed that these effects are additively regulated by OA and ALA in combination when compared to control in OE19 and OE33 esophageal cancer cell lines.
  
  
  CONCLUSIONS
  Our novel mechanistic studies provide evidence for an important role for OA and ALA in esophageal cancer, and suggest that OA and/or ALA might be useful agents in the management or chemoprevention of esophageal cancer.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Laboratory of Metabolic Engineering, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea. Electronic address: mhs72@korea.ac.kr.
authors.forename: Hyun-Seuk
authors.initials: HS
authors.lastname: Moon
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Saime
authors.initials: S
authors.lastname: Batirel
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA 02130, USA.
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D019301:Oleic Acid / Q000494:pharmacology*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
chemical_list: D017962:alpha-Linolenic Acid; D019301:Oleic Acid; D019893:Ribosomal Protein S6 Kinases; D000263:Adenylate Kinase
keywords: AMPK/S6 axis; Alpha Linolenic acid; Esophageal cancer; Malignant potential; Oleic acid