Bergamottin, a natural furanocoumarin abundantly present in grapefruit juice, suppresses the invasiveness of human glioma cells via inactivation of Rac1 signaling.

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.