Quercetin derivative induces cell death in glioma cells by modulating NF-κB nuclear translocation and caspase-3
Cíntia J Kiekow1, Fabrício Figueiró2, Fabrícia Dietrich2
1Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 90610-000, Porto Alegre, RS, Brazil.
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.
Insights
This study explored flavonoids as potential glioma treatments. Chalcone 2 demonstrated significant antitumor effects by inducing apoptosis in glioma cells, offering a promising new avenue for glioblastoma multiforme therapies.
Area of Science:
- Neuro-oncology
- Pharmacology
- Molecular Biology
Background:
- Glioblastoma multiforme (GBM) patients have a poor prognosis, necessitating novel therapeutic strategies.
- Phenolic compounds, such as quercetin, and certain flavonoids show potential for glioma chemotherapy and can cross the blood-brain barrier (BBB).
Purpose of the Study:
- To investigate the antitumor effects of various flavonoids, including chalcones, flavones, flavanones, and flavonols, against gliomas.
- To evaluate the potential of selected flavonoids as therapeutic agents for glioblastoma treatment.
Main Methods:
- Screening of flavonoid activities using the MTT assay in C6 glioma cells.
- Confirmation of chalcone 2's efficacy via Trypan Blue exclusion assay and assessment of its effects on cell cycle and apoptosis.
- Evaluation of cytotoxicity on healthy neural cells using hippocampal organotypic cultures.
Main Results:
- Chalcone 2 exhibited significant antitumor activity in C6 glioma cells at low μM concentrations.
- Chalcone 2 induced apoptosis in glioma cells without altering cell cycle progression.
- Treatments with chalcone 2 were not cytotoxic to healthy hippocampal neural cells.
- Chalcone 2 induced apoptosis through NF-κB inhibition and caspase-3 activation in glioma cells.
Conclusions:
- Chalcone 2 demonstrates potent antitumor effects against glioma cells by inducing apoptosis via specific molecular pathways.
- Chalcone 2 represents a potential prototype for developing novel therapeutic strategies against glioblastoma multiforme.
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