Tetranectin targeting by epigallocatechin gallate suppresses colon cancer cell proliferation

Tetranectin is a serum protein that binds to plasminogen and enhances its proteolytic activation, which underlies the involvement of tetranectin in the development of several carcinomas including colon cancer. In the present study, structure-based in silico screening of natural products showed that epigallocatechin gallate with anticancer effects binds to tetranectin. Binding to epigallocatechin gallate to tetranectin was confirmed by intrinsic fluorescence quenching assays and isothermal titration calorimetry. Furthermore, epigallocatechin gallate efficiently inhibited the activity of tetranectin to enhance the activation of plasminogen. We also found that tetranectin enhanced the proliferation of CT-26 colon cancer cells. Epigallocatechin gallate showed its cytotoxic effect on CT-26 cells due to its binding to tetranectin and the consequent suppression of the cell proliferation. These results demonstrate that the anticancer effect of epigallocatechin gallate is mediated, at least in part, by inhibiting tetranectin as a binding target.