Background
Glioblastoma (GBM) is the most aggressive and frequent primary malignant brain tumor and remains highly resistant to existing treatments. Snake venom disintegrins have potent anticancer activities, but their pharmacological potential against GBM has not been fully explored. In this work, we aimed to evaluate the therapeutic potential of the disintegrin CC8 from Cerastes cerastes snake poison, towards the development of a new anti-GBM drug.
Methods
The effects of CC8 on the viability and proliferation of human GBM cell lines U87, U251, LN229 and LN18 were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet assays. Apoptosis induction was examined by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis of pro- and anti-apoptotic gene expression. The effect of CC8 on cell-extracellular matrix (ECM) interactions was evaluated through adhesion assays and integrin blocking antibodies. The GBM cell infiltration potential was further explored using cell invasion assays and spheroid-based migration models.
Results
CC8 significantly reduced the viability of U87, LN18 and LN229 cells and inhibited the proliferation of U87, while U251 cells showed resistance up to 200 nM. CC8 induced caspase-dependent apoptosis, as shown by downregulation of BCL2 apoptosis regulator (BCL2) and upregulation of BCL2-associated X, apoptosis regulator (BAX), caspase 3 (CASP3), and caspase 8 (CASP8) expression. CC8 also disrupted cell adhesion to fibrinogen (Fg) and fibronectin (Fn) through integrin interference. Furthermore, it markedly reduced GBM cell invasion and reduced U87 spheroid migration.
Conclusions
These findings identify CC8 as a promising venom-derived candidate for GBM drug development, with the potential to improve therapeutic outcomes for this aggressive and treatment-resistant cancer.
Morjen, M., Smati, K., Souissi, C. et al. CC8, a heterodimeric disintegrin from Cerastes cerastes snake venom, triggers apoptosis and limits the proliferation of human glioblastoma cells. Pharmacol. Rep (2026). https://doi.org/10.1007/s43440-026-00846-6
