Apple polyphenol inhibits colon carcinoma metastasis via disrupting Snail binding to focal adhesion kinase

We investigated inhibitory effects of apple polyphenol (AP) in vitro and in vivo. AP significantly suppressed migration, invasion, colony formation and adhesion of DLD-1 cells. AP also reduced expression of tubulin and F-actin, and consequently altered the cytoskeleton structure. AP reduced expression of focal adhesion kinase (FAK) but not talin, α-actinin and vinculin. The activation of FAK downstream effectors paxillin, Src, PI3K and Akt were also inhibited by AP. Moreover, AP inhibited activity but not expression level of FAK-associated GTPase Rac-1, Cdc42 and Rho A. The inhibition of FAK expression by AP was proteasome-independent, which was attributed to interfered binding of Snail to a putative E-box on the FAK promoter. Anti-tumoral and anti-metastatic effects of AP were also demonstrated in vivo. Collectively, AP significantly inhibited motility of DLD-1 cells via disruption of interaction between Snail and the FAK promoter and consequently diminished tumorigenesis and metastasis of DLD-1 cells.