Suppression of oncogene-induced transformation by quercetin and retinoic acid in rat liver epithelial cells.
AP1 is a heterodimeric complex containing products of the Jun and Fos oncogene families. The c-fos and c-jun protooncogenes act as transcriptional activator for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. In this study, to show evidence of a possible inhibition of AP1 transcriptional activity in molecular mechanisms of foodborne molecules, known to be negative modulators of carcinogenesis, we established two rat liver epithelial (REL) cell lines overexpressing either c-fos (43C line) or c-jun (RELcJ1 line) oncoproteins. Contrary to the 43C line, which was spontaneously transformed, the c-jun-transfected REL cells were only transformed in vitro after 12-O-tetra-decanoylphorbol 13-acetate (TPA) exposure. All trans-retinoic acid (RA) abolished the transformation of the 43C line and TPA-treated RELcJ1 cells, suggesting that RA could decrease AP1 activity in these cells despite c-fos or c-jun overexpression. Furthermore, we show for the first time that a flavonoid, quercetin, which is a natural component of vegetables, inhibited only the transformation of the 43C line. The spontaneous transformation of the c-fos-transfected REL cells was associated with the appearance of c-fos/AP1 complexes binding TRE, suggesting that c-fos/AP1 complexes are involved in the antitransforming mechanism of quercetin.
Lagarrigue
S
S
Laboratoire de Nutrition et Sécurité Alimentaire, INRA, Jouy-en-Josas, France.
Chaumontet
C
C
Heberden
C
C
Martel
P
P
Gaillard-Sanchez
I
I
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D005502:Food; D016762:Genes, fos / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011794:Quercetin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D014162:Transfection; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D005419:Flavonoids; D009838:Oligodeoxyribonucleotides; D018808:Transcription Factor AP-1; D014212:Tretinoin; D011794:Quercetin