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

作者：Hung Chia Hung; Huang Chi Chou; Hsu Li Sung; Kao Shao Hsuan^*; Wang Chau Jong

来源：Journal of Functional Foods, 2015, 12: 80-91.

DOI：10.1016/j.jff.2014.10.031

• Colon cancer
• Metastasis
• Apple polyphenol
• 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 (FAX) but not talin, alpha-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 FAX-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.

• 出版日期2015-1