Naringenin Exhibits Antiglioma Activity Related to Aryl Hydrocarbon Receptor Activity and IL-6, CCL2, and TNF-α Expression

Author(s)

de Santana, Monique Reis ; Argolo, Deivison Silva ; Lima, Irla Santos ; Santos, Cleonice Creusa dos ; Victor, Mauricio Moraes ; Ramos, Gabriel dos Santos ; do Nascimento, Ravena Pereira ; Ulrich, Henning ; Costa, Silvia Lima

• Document type: Journal article
• Source: BRAIN SCIENCES; v. 15, n. 3, p. 13-pg., 2025-03-20.

Abstract

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 mu M) alone or in combination with the AhR agonist indole-3-carbinol (50 mu M) 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-alpha) 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. (AU)

• FAPESP's process: 23/17147-6 - Treatment of chemoresistant human glioblastoma cells with DNA aptamers for the development of new adjuvant therapies
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Regular Research Grants