Quercetin suppresses the migration of hepatocellular carcinoma cells stimulated by hepatocyte growth factor or transforming growth factor-a: Attenuation of AKT signaling pathway

Flavonol, which is found abundantly in plants such as fruits and vegetables, belongs to the family of flavonoid, natural polyphenols. Quercetin, one of the flavonol, reportedly has anti-cancer effects and prevents the proliferation of various cancer cells, including hepatocellular carcinoma (HCC). However, the effects of quercetin on HCC cells migration have not yet been clarified. We have previously shown that the migration of human HCCderived HuH7 cells induced by hepatocyte growth factor (HGF) or transforming growth factor-alpha (TGF-alpha) is mediated through p38 MAPK and AKT. In this study, we investigated whether quercetin affects the HGF- or TGF-alpha-induced migration of HuH7 cells. Quercetin significantly suppressed both HGF- and TGF-alpha-induced migration of HuH7 cells in a dose-dependent manner. In addition, myricetin, another flavonol, also showed significant inhibition of the cell migration. Each HGF- and TGF-alpha-induced autophosphorylation of receptors were not affected by quercetin or myricetin. Quercetin did not suppress HGF- or TGF-alpha-induced p38 MAPK phosphorylation. On the contrary, quercetin and myricetin inhibited the growth factors-induced phosphorylation of AKT. Our results strongly suggest that quercetin suppresses the growth factor-induced migration of HCC cells by inhibiting the signaling pathway of AKT but not p38 MAPK.