柚皮素表现出与芳烃受体活性以及白细胞介素-6、趋化因子配体2和肿瘤坏死因子-α表达相关的抗胶质瘤活性。

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

作者信息

Santana Monique Reis de, Argolo Deivison Silva, Lima Irlã Santos, Santos Cleonice Creusa Dos, Victor Maurício Moraes, Ramos Gabriel Dos Santos, Nascimento Ravena Pereira do, Ulrich Henning, Costa Silvia Lima

机构信息

Laboratory of Neurochemistry and Cellular Biology, Institute of Health Sciences, Federal University of Bahia, Salvador 40231-300, Brazil.

Department of Organic Chemistry, Institute of Chemistry, Federal University of Bahia, Salvador 40231-300, Brazil.

出版信息

Brain Sci. 2025 Mar 20;15(3):325. doi: 10.3390/brainsci15030325.

DOI:10.3390/brainsci15030325

PMID:40149846

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11940588/

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 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.

摘要

背景

胶质母细胞瘤（GBM）是一种高度侵袭性的脑肿瘤，其特征为细胞快速增殖、侵袭行为和化疗耐药性。芳烃受体（AhR）与化疗耐药性和免疫逃逸有关，使其成为一个有前景的治疗靶点。黄酮类等天然化合物因其抗炎、抗氧化和抗癌特性而受到关注。其中，柚皮素是一种源自柑橘的黄酮类化合物，具有抗增殖、促凋亡和免疫调节作用。