Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase. A previous study demonstrated that 3'-deoxyadenosine (also known as cordycepin) suppresses the expression of integrins and FAK as well as cell migration and EMT in the HCC. However, the mechanism that cordycepin influences FAK expression and angiogenesis in the endothelial cells (ECs) remains unclear. In this study, we found that cordycepin suppresses FAK expression and phosphorylation of FAK at Tyr397 in ECs. Cordycepin inhibits cell proliferation, migration and tube formation of ECs. Intriguingly, result of confocal microscopy analysis reveals that cordycepin reduces FAK expression in the cytoplasm but not in the focal adhesions. Finally, we demonstrate that cordycepin significantly suppresses angiogenesis and reduces tumor growth in an in vivo matrigel assay and a xenograft nude mice model. Taken together, our study indicates that cordycepin attenuates cell proliferation and migration which may result in impairment of angiogenesis process and tumor growth via downregulation of FAK expression and induction of p53 and p21 in ECs. As a result, cordycepin could be considered as a potential adjuvant for cancer therapy.
