The inhibitory effect of anthocyanins on Akt on invasion and epithelial-mesenchymal transition is not associated with the anti-EGFR effect of the anthocyanins

Abstract

Evidence suggests that anthocyanins inhibit EGFR and Akt activity. However, it is still unknown whether the inhibitory effect of anthocyanins on Akt is associated with the anti-EGFR effect. The effect of anthocyanins on epithelial-mesenchymal transition (EMT) has not been extensively studied. Therefore, we investigated the effects of anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) on EGF-induced EMT and the underlying molecular mechanisms. AIMs suppressed the invasion of A549 cells in a dose-dependent manner. AIMs inhibited the phosphorylation of Akt and EGFR, but the inhibitory effect on Akt was not derived from EGFR. EGF re-induced Akt phosphorylation at Thr308 in the AIM-treated cells, but not Akt phosphorylation at Ser473. AIMs also inhibited EMT of cancer cells. AIMs inhibited glycogen synthase kinase-3β phosphorylation and β-catenin expression that are invovled in EMT. We confirmed these findings with transforming growth factor (TGF)-β. In conclusion, these data suggest that the inhibitory effect of AIMs on Akt activity is independent of EGFR, and that AIMs suppressed invasion and migration at least in part by suppressing EMT by inhibiting Akt activity as well as EGFR. This study provides evidence that AIMs may have anticancer effects on human cancer cells.