Flavonoids suppress human glioblastoma cell growth by inhibiting cell metabolism, migration, and by regulating extracellular matrix proteins and metalloproteinases expression

• Flavonoids reduced proliferation, viability, invasion and filopodias of GL-15 glioblastoma cells.
• Flavonoids induced a decrease in levels of MMPs expression and activity.
• Flavonoids regulated expression of MEC components fibronectin and laminin.
• Glioblastoma cells exposed to flavonoids presented mitochondrial damage, vacuolation and entered in apoptosis.
• Flavonoids induced astroglial differentiation in remaining glioblastoma cells.

The malignant gliomas are very common primary brain tumors with poor prognosis, which require more effective therapies than the current used, such as with chemotherapy drugs. In this work, we investigated the effects of several polyhydroxylated flavonoids namely, rutin, quercetin (F7), apigenin (F32), chrysin (F11), kaempferol (F12), and 3′,4′-dihydroxyflavone (F2) in human GL-15 glioblastoma cells. We observed that all flavonoids decreased the number of viable cells and the mitochondrial metabolism. Furthermore, they damaged mitochondria and rough endoplasmic reticulum, inducing apoptosis. Flavonoids also induced a delay in cell migration, related to a reduction in filopodia-like structures on the cell surface, reduction on metalloproteinase (MMP-2) expression and activity, as well as an increase in intra- and extracellular expression of fibronectin, and intracellular expression of laminin. Morphological changes were also evident in adherent cells characterized by the presence of a condensed cell body with thin and long cellular processes, expressing glial fibrillary acidic protein (GFAP). Therefore, these flavonoids should be tested as potential antitumor agents in vitro and in vivo in other malignant glioma models.