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Naringenin Exhibits Antiglioma Activity Related to Aryl Hydrocarbon Receptor Activity and IL-6, CCL2, and TNF-α
Monique Reis de Santana1, Deivison Silva Argolo1, Irlã Santos Lima1
1Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil.
Background:
Glioblastoma (GBM) is a highly aggressive brain tumor characterized by rapid cell proliferation, invasive behavior, and chemoresistance. The aryl hydrocarbon receptor (AhR) is implicated in chemoresistance and immune evasion, making it a promising therapeutic target. Natural compounds such as flavonoids have gained attention for their anti-inflammatory, antioxidant, and anticancer properties. Among them, naringenin, a citrus-derived flavonoid, exerts antiproliferative, pro-apoptotic, and immunomodulatory effects.
Objectives:
This study investigated the antiglioma effects of the flavonoid naringenin on the viability, growth, and migration of glioma cells and its potential role as an AhR modulator.
Methods:
Human (U87) and rat (C6) glioma cell lines were exposed to naringenin (10-300 µM) alone or in combination with the AhR agonist indole-3-carbinol (50 µM) for 24 to 48 h. Cell viability, scratch wound, and cell migration assays were performed. The expression of inflammatory markers was also analyzed by RT-qPCR.
Results:
Naringenin exerted dose- and time-dependent inhibition of cell viability and migration. The treatment decreased the gene expression of interleukin-6 (IL-6) and chemokine (CCL2), alongside increased tumor necrosis factor-alpha (TNF-α) expression, an effect reversed by the AhR agonist.
Conclusions:
These findings highlight naringenin's potential as an antiglioma agent and its role in AhR signaling.
Insights
Naringenin, a flavonoid, effectively inhibits glioma cell growth and migration by influencing aryl hydrocarbon receptor (AhR) signaling. This natural compound shows promise as a potential antiglioma therapeutic agent.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with chemoresistance and immune evasion.
- The aryl hydrocarbon receptor (AhR) is a key target for GBM therapy.
- Naringenin, a flavonoid, possesses anticancer and immunomodulatory properties.
Purpose of the Study:
- Investigate naringenin's antiglioma effects on cell viability, growth, and migration.
- Determine naringenin's role as an aryl hydrocarbon receptor (AhR) modulator in glioma cells.
Main Methods:
- Utilized human (U87) and rat (C6) glioma cell lines.
- Treated cells with naringenin alone or with an AhR agonist (indole-3-carbinol).
- Assessed cell viability, migration, and inflammatory marker gene expression (IL-6, CCL2, TNF-α).
Main Results:
- Naringenin demonstrated dose- and time-dependent inhibition of glioma cell viability and migration.
- Naringenin decreased interleukin-6 (IL-6) and chemokine (CCL2) expression.
- Naringenin increased tumor necrosis factor-alpha (TNF-α) expression, an effect modulated by the AhR agonist.
Conclusions:
- Naringenin exhibits significant potential as an antiglioma agent.
- Naringenin influences aryl hydrocarbon receptor (AhR) signaling pathways.
- Naringenin's effects on inflammatory markers suggest immunomodulatory roles in GBM.
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