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

Metabolism. 2014 Nov;63(11):1447-54. doi: 10.1016/j.metabol.2014.07.009. Epub 2014 Jul 25.


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.

Materials/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.

Keywords: AMPK/S6 axis; Alpha Linolenic acid; Esophageal cancer; Malignant potential; Oleic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenylate Kinase / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects*
  • Esophageal Neoplasms / enzymology
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Humans
  • Oleic Acid / pharmacology*
  • Ribosomal Protein S6 Kinases / metabolism*
  • alpha-Linolenic Acid / pharmacology*


  • alpha-Linolenic Acid
  • Oleic Acid
  • Ribosomal Protein S6 Kinases
  • Adenylate Kinase