Heparin-incorporated whey protein isolate-derived hydrogels with an intended dual function as snakebite wound dressings and drug delivery systems inhibit spitting cobra venom-induced cytotoxicity

Posted by

CC8, a heterodimeric disintegrin from Cerastes cerastes snake venom, triggers apoptosis and restrains the dissemination of human glioblastoma cells

Posted by

 

By Holger Krisp - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=17570143

CC8, a heterodimeric disintegrin from Cerastes cerastes snake venom, triggers apoptosis and restrains the dissemination of human glioblastoma cells

Abstract

Background

Glioblastoma (GBM) is the most aggressive and frequent primary malignant brain tumor and remains highly resistant to existing therapies. Snake-venom disintegrins possess potent anticancer activities, yet their pharmacological potential against GBM is not fully explored. In this work, we aimed to evaluate the therapeutic potential of the disintegrin CC8 from Cerastes cerastes snake venom, toward the development of a novel 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. 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, whereas U251 cells showed resistance up to 200 nM. CC8 induced caspase-dependent apoptosis, as evidenced 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 decreased GBM cell invasion and reduced U87 spheroid migration.

Conclusions

These findings identify CC8 as a promising venom-derived candidate for GBM drug development, with 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 restrains the dissemination of human glioblastoma cells. Pharmacol. Rep (2026). https://doi.org/10.1007/s43440-026-00846-6