El bisfenolato de dimetilo inhibe el crecimiento del glioblastoma al promover la detención del ciclo celular y la...

Glioblastoma (GBM) is a highly invasive brain tumor. Temozolomide (TMZ) is the standard first-line chemotherapy for GBM, but its efficacy is often limited by the development of resistance and serious side effects, most notably myelosuppression. We recently synthesized Dimethyl bisphenolate (DMB), a novel natural neolignan derivative that has a core structure perhaps greatly associated with anti-tumor activity. However, DMB has only been reported to exhibit hepatoprotective activity thus far, and its anti-tumor activity remains to be investigated. The aim of this study was to explore the effects, and mechanisms, and potential in vivo application of DMB as a treatment for GBM. We first used CCK-8, colony formation, and migration/invasion assays to evaluate the effects of DMB on the biological behaviors of GBM cells. We then investigated the anti-GBM mechanism of DMB through bioinformatics, flow cytometry, and western blot analyses, followed by an assessment of the in vivo anti-GBM activity and safety of DMB using BALB/c nude mouse xenograft models. DMB significantly inhibited the viability, colony formation, and migration of GBM cells. Bioinformatics analysis and subsequent experiments confirmed that DMB's antitumor mechanism involves inhibition of GBM cell proliferation through the p53 pathway-mediated cell cycle arrest and promotion of apoptosis via the mitochondrial Reactive oxygen species (ROS)-mediated apoptotic pathway. Compared to the first-line drug TMZ, DMB exhibited superior anti-GBM activity at high doses, with no evidence of myelosuppression or hepatorenal toxicity within the tested dose range. Therefore, DMB has potential for development as an anti-GBM drug.