A possible molecular mechanism of two flavones and two flavonols on the induction of differentiation in a human oesophageal adenocarcinoma cell line (OE33)

Abstract

The influences of two flavones (baicalein, chrysin) and two flavonols (galangin, kaempferol) selected on induction of differentiation in a human esophageal adenocarcinoma (OE33) cell line were studied in the present work. All compounds selected could be able to inhibit proliferation of OE33 cells in a dose- and time-dependent manner. The inhibitory potency of these compounds on OE33 cells was in the order of: galangin > chrysin > baicalein >kaempferol. OE33 cells treated with these compounds for 24 h showed differentiation characteristics including the differentiation-specific morphological changes, the augmentation of differentiation markers and the inhibition of human telomerase reverse transcriptase. The potency of these compounds on induction of differentiation of OE33 cells was similar to that of them on growth inhibition. To reveal the possible molecular mechanisms by which these compounds modulate proliferation and differentiation in OE33 cells, the alterations of three genes, 14-3-3s, cyclin B1 and cyclin D1, which are related to proliferation and differentiation of cells, were investigated by real-time polymerase chain reaction (RT-PCR) and Western blot. The results showed that up-regulation of 14-3-3s and down-regulation of cyclin B1 and cyclin D1 at the mRNA and protein levels were observed in OE33 cells treated with these compounds, indicating that 14-3-3s, cyclin B1 and cyclin D1 might be target genes of these flavonoids in inducing differentiation of OE33 cells. Key words: Flavones, flavonols, differentiation, esophageal cancer, molecular mechanism.