Abstract
The aim of the present study was to explore the effect of bergamottin, a natural furanocoumarin obtained from grapefruit juice, on the invasiveness of human glioma cells. The results revealed that treatment with bergamottin for 48 h significantly inhibited wound-healing migration and Matrigel invasion of human glioma cells, compared with untreated cells (P<0.05). Bergamottin treatment caused a significant decrease in the expression and secretion of matrix metalloproteinase (MMP)-9 in glioma cells compared with untreated cells (P<0.05). A Rac1-GTP pull-down assay demonstrated that bergamottin-treated glioma cells had a significantly decreased level of active Rac1-GTP compared with untreated cells (P<0.05). However, bergamottin had no significant effect on cell division cycle 42 activity. Expression of constitutively activated Rac1 almost completely restored the migration and invasion of bergamottin-treated glioma cells. In addition, bergamottin-induced downregulation of MMP-9 was prevented by exogenous activated Rac1. The results of the present study demonstrated that bergamottin exhibits anti-invasive activity in human glioma cells through the inactivation of Rac1 and downregulation of MMP-9.