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 transcrip tional activator for numerous cellular genes, and the overexpression o f these genes may cause malignant transformation. In this study, to sh ow evidence of a possible inhibition of AP1 transcriptional activity i n molecular mechanisms of foodborne molecules, known to be negative mo dulators of carcinogenesis, we established two rat liver epithelial (R EL) 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 a ctivity in these cells despite c-fos or c-jun overexpression. Furtherm ore, we show for the first time that a flavonoid, quercetin, which is a natural component of vegetables, inhibited only the transformation o f the 43C line. The spontaneous transformation of the c-fos-transfecte d REL cells was associated with the appearance of c-fos/AP1 complexes binding TRE, suggesting that c-fos/AP1 complexes are involved in the a ntitransforming mechanism of quercetin.