TY - JOUR
T1 - 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
AU - Moon, Hyun Seuk
AU - Batirel, Saime
AU - Mantzoros, Christos S.
N1 - Funding Information:
This work was supported by the National Institutes of Health (DK081913) and the Clinical Science Research and Development Service of the VA Office of Research and Development (1I01CX000422-01A1). The Laboratory of Metabolic Engineering is supported by Korea University Grant. The Mantzoros Laboratory is supported by a discretionary grant from Beth Israel Deaconess Medical Center.
Publisher Copyright:
© 2014 Elsevier Inc. All rights reserved.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
KW - AMPK/S6 axis
KW - Alpha Linolenic acid
KW - Esophageal cancer
KW - Malignant potential
KW - Oleic acid
UR - http://www.scopus.com/inward/record.url?scp=84908024760&partnerID=8YFLogxK
U2 - 10.1016/j.metabol.2014.07.009
DO - 10.1016/j.metabol.2014.07.009
M3 - Article
C2 - 25129649
AN - SCOPUS:84908024760
VL - 63
SP - 1447
EP - 1454
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
SN - 0026-0495
IS - 11
ER -