| Full text | |
| Author(s): |
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
Total Authors: 8
|
| Document type: | Journal article |
| Source: | PHARMACOLOGICAL REPORTS; v. N/A, p. 12-pg., 2025-03-08. |
| Abstract | |
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) | |
| FAPESP's process: | 21/11606-3 - Investigation of the antineoplastic effects of novel PIP4K2 and HDAC inhibitors in hematologic malignancies |
| Grantee: | João Agostinho Machado Neto |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 23/12246-6 - Evaluation of the antineoplastic effects of the multikinase inhibitor AD80 in hematologic malignancies with constitutive activation of tyrosine-kinase pathways |
| Grantee: | João Agostinho Machado Neto |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 20/12842-0 - Impact of genetic ancestry on development, molecular characteristics and clinical outcome in adult patients with Acute Lymphoblastic Leukemia |
| Grantee: | Keli Cristina de Lima |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 22/11038-8 - Investigation of ANKHD1-related signaling pathways and biological processes in Stomach Cancer |
| Grantee: | Bruna Oliveira de Almeida |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 22/03316-8 - Investigation of the effects of the multikinase inhibitor AD80 in hematological neoplasms with constitutive activation of tyrosine kinase pathways |
| Grantee: | Lívia Bassani Lins de Miranda |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |