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

IF 2.8 3区医学 Q3 NEUROSCIENCES Brain Sciences Pub Date : 2025-03-20 DOI:10.3390/brainsci15030325

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

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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.

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柚皮素显示抗胶质瘤活性与芳烃受体活性和IL-6、CCL2和TNF-α表达有关。

背景：胶质母细胞瘤（GBM）是一种高度侵袭性的脑肿瘤，其特点是细胞快速增殖、侵袭性行为和化疗耐药。芳烃受体（aryl hydrocarbon receptor, AhR）与化学耐药和免疫逃避有关，是一个很有前景的治疗靶点。类黄酮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类黄酮，具有抗增殖、促凋亡和免疫调节作用。目的：研究柚皮素类黄酮对胶质瘤细胞活力、生长和迁移的影响及其作为AhR调节剂的潜在作用。方法：将人（U87）和大鼠（C6）胶质瘤细胞系单独暴露于柚皮素（10-300µM）或与AhR激动剂吲哚-3-甲醇（50µM）联合暴露24 - 48小时。进行细胞活力、划伤和细胞迁移测定。RT-qPCR分析炎症标志物的表达。结果：柚皮素对细胞活力和迁移具有剂量依赖性和时间依赖性。治疗降低了白细胞介素-6 （IL-6）和趋化因子（CCL2）的基因表达，同时增加了肿瘤坏死因子-α (TNF-α)的表达，这一作用被AhR激动剂逆转。结论：这些发现突出了柚皮素作为抗胶质瘤药物的潜力及其在AhR信号传导中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Sciences Neuroscience-General Neuroscience

CiteScore

4.80

自引率

9.10%

发文量

1472

审稿时长

18.71 days

期刊介绍： Brain Sciences (ISSN 2076-3425) is a peer-reviewed scientific journal that publishes original articles, critical reviews, research notes and short communications in the areas of cognitive neuroscience, developmental neuroscience, molecular and cellular neuroscience, neural engineering, neuroimaging, neurolinguistics, neuropathy, systems neuroscience, and theoretical and computational neuroscience. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.