Research Information System
Chemico-Biological Interactions, vol.435, 2026 (SCI-Expanded, Scopus)
Glioblastoma (GB) is one of the most aggressive brain tumours, with low survival rates despite combined radiation and chemotherapy. The blood-brain barrier (BBB) limits the delivery and efficacy of many chemotherapeutic agents, highlighting the need for more effective and alternative therapeutic strategies. 5-Ethynyl-2-deoxyuridine (EdU), a thymidine analogue capable of crossing the BBB, has recently been investigated for its effects on cellular processes in glioma, particularly in relation to replication stress and DNA damage responses. This study aimed to investigate the effects of EdU on apoptosis, autophagy, and cell cycle regulation in U87-MG glioma cells (PTEN mutant, p53 wild-type) using both 2D monolayer and 3D spheroid culture models. EdU exposure significantly reduced glioma cell proliferation and migration, was associated with increased apoptotic markers including cleaved caspase-3, and modulated autophagy-related markers including LC3A, LAMP2A, and HSC70 expression. Moreover, EdU exposure was associated with alterations in epithelial-mesenchymal transition (EMT) markers, including decreased N-cadherin and β-catenin and increased E-cadherin levels, and with reduced nuclear translocation of Hsp70.In 3D spheroid cultures, 50 μM EdU significantly reduced spheroid growth and migration, supporting its biological activity in a physiologically relevant model. These findings suggest that EdU-induced cellular stress responses may represent a potential area for further investigation in glioblastoma, particularly in relation to autophagy and apoptosis. Further studies are warranted to better understand the underlying mechanisms and potential applications of EdU in glioblastoma.