Esculetin Attenuates the Migration and Invasion of Human Hepatocellular Carcinoma Cells by Attenuating Matrix Metalloproteinase Activity and Strengthening Tight Junctions.

Hepatocellular carcinoma (HCC) is a highly malignant liver cancer that metastasizes to various organs. Esculetin, a natural dihydroxy coumarin derivative, has been shown to have a variety of pharmacological properties, including immune-enhancing, antioxidant, and anti-inflammatory effects. Esculetin is also known to have potent anticancer activity; however, studies on its ability to inhibit cancer cell metastasis are relatively rare. In this study, we investigated how esculetin inhibits the migration and invasion of human hepatocellular carcinoma cell lines Hep3B and HepG2, and elucidated the underlying mechanisms. Our results showed that esculetin markedly suppressed the migration and invasion of HCC cells, and this was associated with a decrease in the expression and activity of matrix metalloproteinase (MMP)-9 and MMP-2, and increased expression levels of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. In addition, esculetin enhanced the tightening of tight junctions by suppressing the expression of claudin family proteins.