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.
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.