Eribulin exerts multitarget antineoplastic activity in glioma cells.

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Guilherme Augusto Sousa Alcântara, Mariane Cristina do Nascimento, Livia Bassani Lins de Miranda, Bruna Oliveira de Almeida, Keli Lima, Eduardo Magalhães Rego, Leticia Veras Costa-Lotufo, João Agostinho Machado-Neto
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引用次数: 0

Abstract

Background: Gliomas, particularly glioblastomas, are highly aggressive cancers with rapid proliferation and poor prognosis. Current treatments have limited efficacy, highlighting the need for new therapeutic strategies. Eribulin mesylate, a synthetic macrocyclic ketone, has shown potential as an anticancer agent in several malignancies. This study investigates the cellular and molecular effects of eribulin in glioma models, focusing on its impact on cell cycle progression, apoptosis, mitochondrial function, and migration.

Methods: Glioma cell lines were treated with eribulin. Cell viability was measured by MTT assay, and the cell cycle was analyzed by flow cytometry. Apoptosis was assessed through morphological changes, PARP1 cleavage, and γH2AX expression. Mitochondrial integrity and reactive oxygen species levels were evaluated by flow cytometry. Cell migration was assessed using a spheroid-based assay, and protein expression changes were analyzed by Western blotting.

Results: Eribulin reduced cell viability, with HOG cells exhibiting the highest sensitivity. Cell cycle analysis showed G2/M phase arrest and morphological examination revealed polyploidy and apoptotic features. Mitochondrial dysfunction was observed, with decreased mitochondrial membrane potential and increased reactive oxygen species, particularly in HOG and T98G cells. Molecular analysis indicated activation of apoptotic pathways (PARP1 cleavage and γH2AX elevation) and reduced stathmin 1 expression. Eribulin also significantly reduced cell migration in HOG cells.

Conclusion: Eribulin demonstrates potent anti-glioma effects through apoptosis, mitochondrial dysfunction, and cell cycle disruption. These findings support its potential as a therapeutic option for glioblastoma treatment, warranting further investigation into its mechanisms and clinical applicability.

艾力布林对胶质瘤细胞具有多靶点抗肿瘤活性。
背景:胶质瘤,尤其是胶质母细胞瘤,是一种侵袭性极强的癌症,增殖迅速,预后不良。目前的治疗方法疗效有限,因此需要新的治疗策略。甲磺酸伊瑞布林是一种合成的大环酮,已显示出作为抗癌剂治疗多种恶性肿瘤的潜力。本研究调查了艾瑞布林在胶质瘤模型中的细胞和分子效应,重点研究其对细胞周期进展、细胞凋亡、线粒体功能和迁移的影响:方法:用麦瑞布林处理胶质瘤细胞系。方法:用艾瑞布林处理胶质瘤细胞系,用 MTT 法测定细胞活力,用流式细胞术分析细胞周期。通过形态变化、PARP1裂解和γH2AX表达评估细胞凋亡。线粒体完整性和活性氧水平通过流式细胞术进行评估。细胞迁移采用球形试验进行评估,蛋白质表达变化采用 Western 印迹法进行分析:结果:Eribulin 降低了细胞活力,其中 HOG 细胞的敏感性最高。细胞周期分析显示 G2/M 期停滞,形态学检查显示多倍体和凋亡特征。观察到线粒体功能障碍,线粒体膜电位降低,活性氧增加,尤其是在 HOG 和 T98G 细胞中。分子分析表明,细胞凋亡途径被激活(PARP1 断裂和 γH2AX 升高),stathmin 1 表达减少。Eribulin 还能明显减少 HOG 细胞的迁移:结论:Eribulin 可通过细胞凋亡、线粒体功能障碍和细胞周期破坏等途径发挥强效抗胶质瘤作用。这些发现支持其作为胶质母细胞瘤治疗选择的潜力,值得进一步研究其机制和临床适用性。
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来源期刊
Pharmacological Reports
Pharmacological Reports 医学-药学
CiteScore
8.40
自引率
0.00%
发文量
91
审稿时长
6 months
期刊介绍: Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures. Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology. Studies of plant extracts are not suitable for Pharmacological Reports.
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