“Glioblastoma remains one of the most aggressive and treatment-resistant malignancies. Current treatment options, such as radio- and chemotherapy, induce oxidative stress-mediated DNA damage leading to cancer cell death, but are also neurotoxic and not efficient in long term.
Our study investigated the effects of cannabidiol, celecoxib and 2,5-dimethylcelecoxib, individually and in combinations, on U-138 MG glioblastoma cell survival, oxidative stress, canonical and non-canonical Nrf2 pathway activation, cell migration and apoptosis.
Using the MTT and flow cytometry assay we found that the analyzed compounds and their combinations induce dose-dependent, synergistic, and oxidative stress-related cytotoxicity, with minimal impact (at the concentrations exhibiting anti-cancer effects) on non-cancerous human astrocyte (HA) cell line.
The Nrf2 ELISA assay was used for the analysis of the nuclear binding of the nuclear factor-2 erythroid related factor-2 (Nrf2), which followed by the RT-qPCR and Western blot analysis, confirmed the antioxidant response of cells to the applied treatments. Diminished migratory potential, and increase of the autophagy-related p62, LC3 and apoptosis-related caspase-3 protein levels were also observed in response to the treatment with the analyzed compounds.
Overall, our study provides evidence that cannabidiol combined with celecoxib or 2,5-dimethylcelecoxib may represent a promising strategy for glioblastoma treatment.”
https://pubmed.ncbi.nlm.nih.gov/41089524/
“In conclusion, the combination of CBD with celecoxib or 2,5-DMC represents a promising therapeutic strategy for glioblastoma. While CBD alone induces cytotoxicity, ROS production, and apoptosis, our synergy analysis demonstrates that combining CBD with celecoxib or 2,5-DMC allows effective killing of GBM cells at lower CBD concentrations. “