Pinocembrin suppresses TGF-β1-induced epithelial-mesenchymal transition and metastasis of human Y-79 retinoblastoma cells through inactivating αvβ3 integrin/FAK/p38α signaling pathway

Background: Pinocembrin is the most abundant flavonoid in propolis. In this study, we investigated the antimetastatic effect of pinocembrin on TGF-beta 1-induced epithelial-mesenchymal transition (EMT) and metastasis of human Y-79 retinoblastoma cells. Results: Firstly, the results showed that pinocembrin significantly suppresses the TGF-beta 1-induced abilities of the invasion and migration of Y-79 cells under non-cytotoxic concentration. Pinocembrin decreased TGF-beta 1-induced expression of vimentin, N-cadherin, alpha v and beta 3 integrin in Y-79 cells. Molecular data also showed pinocembrin inhibits the activation of focal adhesion kinase (FAK) and p38 alpha signal involved in the downregulation of enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-2/9 (MMP-2/-9) induced by TGF-beta 1. Next, pinocembrin also strongly inhibited the degradation of inhibitor of kappaB alpha (I kappa B alpha) and the nuclear levels of nuclear factor kappa B (NF-kappa B). Also, a dose-dependent inhibition on the binding ability of NF-kappa B was further observed under pinocembrin treatment. Conclusions: Presented results indicated that pinocembrin inhibits TGF-beta 1-induced epithelial-mesenchymal transition ( EMT) and metastasis of Y-79 cells by inactivating the alpha v beta 3 integrin/FAK/p38 alpha signaling pathway. Thus, our findings point to the anticancer potential of pinocembrin against retinoblastoma cells.