Eribulin exerts multitarget antineoplastic activity in glioma cells

Autor(es)

Alcantara, Guilherme Augusto Sousa ; do Nascimento, Mariane Cristina ; de Miranda, Livia Bassani Lins ; de Almeida, Bruna Oliveira ; Lima, Keli ; Rego, Eduardo Magalhaes ; Costa-Lotufo, Leticia Veras ; Machado-Neto, Joao Agostinho

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOLOGICAL REPORTS; v. N/A, p. 12-pg., 2025-03-08.

Resumo

BackgroundGliomas, 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.MethodsGlioma 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 gamma H2AX 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.ResultsEribulin 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 gamma H2AX elevation) and reduced stathmin 1 expression. Eribulin also significantly reduced cell migration in HOG cells.ConclusionEribulin 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. (AU)

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