Conjugated linoleic acid inhibits Caco-2 cell growth via ERK-MAPK signaling pathway.
Conjugated linoleic acid (CLA) is a naturally occurring compound found in dairy and beef products. In recent years, it has received considerable attention because several studies showed a lower incidence of certain cancers in animals fed CLA-supplemented diets. In vitro studies further showed growth inhibitory activity on tumor cell proliferation, the CLA being effective above all against colon cancer cells. The aim of the present work was to investigate the growth inhibitory effect of CLA on Caco-2 cell line. Under our experimental conditions, CLA repressed Caco-2 cell proliferation, and the growth-inhibitory action increased by repeating treatments. However, in Caco-2 cells, CLA was unable to induce apoptosis, as revealed by cell-cycle analysis and Western blot studies. To determine the mechanism by which CLA inhibits cell growth, we studied its effect on extracellular-regulated kinase signaling. Conjugated linoleic acid reduced expression levels of Raf-1 and phosphorylation of ERK1/2, which was accompanied by a decrease in the expression of the downstream transcription factor c-myc. Our data suggest that CLA is dependent, at least in part, on the ERK kinase pathway for its ability to inhibit the growth of Caco-2 cancer cells.
Bocca
Claudia
C
Department of Experimental Medicine and Oncology, University of Torino, 10125, Torino, Italy.
Bozzo
Francesca
F
Gabriel
Ludovica
L
Miglietta
Antonella
A
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D018938:Caco-2 Cells / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019908:Proto-Oncogene Proteins c-raf / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000187:drug effects / Q000378:metabolism
C494772:BAK1 protein, human; D044243:Linoleic Acids, Conjugated; D050998:bcl-2 Homologous Antagonist-Killer Protein; D007770:L-Lactate Dehydrogenase; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3