Quercetin derivative induces cell death in glioma cells by modulating NF-κB nuclear translocation and caspase-3 activation

Abstract

Treated glioblastoma multiforme (GBM) patients only survive 6 to 14months after diagnosis; therefore, the development of novel therapeutic strategies to treat gliomas remains critically necessary. Considering that phenolic compounds, like quercetin, have the potential to be used in the chemotreatment of gliomas and that some flavonoids exhibit the ability to cross the BBB, in the present study, we investigated the antitumor effect of flavonoids (including chalcones, flavones, flavanones and flavonols). Initially their activities were tested in C6 glioma cells screened using the MTT method, resulting in the selection of chalcone 2 whose feasibility was confirmed by a Trypan Blue exclusion assay in the low μM range on C6 glioma cells. Cell cycle and apoptotic death analyses on C6 glioma cells were also performed, and chalcone 2 increased the apoptosis of the cells but did not alter the cell cycle progression. In addition, treatments with these two compounds were not cytotoxic to hippocampal organotypic cultures, a model of healthy neural cells. Furthermore, the results indicated that 2 induced apoptosis by inhibition of NF-κB and activation of active caspase-3 in glioma cells, suggesting that it is a potential prototype to develop new treatments for GBM in the future.

Keywords: 2′,4′-Dihydroxy-4-methoxychalcone (PubChem CID: 166795); 3,3′,5,5′-Tetramethoxychalcone (PubChem CID: 51355269); 7-Hydroxy-4′-methoxyflavone (PubChem CID: 5320693); Antitumoral; Apoptosis; Chalcone; Glioma; Morin (PubChem CID: 5281670); NF-κB; Polyphenol; Quercetin (PubChem CID: 5280343).