Gamma-Irradiated Phospholipase D from Loxosceles devia Venom as a Potential Inducer of Apoptosis in Normal Breast Cells and Necrosis in Breast Cancer Cells: An Experimental and Computer Simulation Perspe
A Heredia-Barbero, L E Arias-Romero, B L Ávila-Suárez, A N Rivera-Molina, O Villamar-Cruz, G Gil-Alarcón, A Alagón, C C Camargo-RayaAbstract
Background and Aims
This study explores the effect of gamma-irradiated venom from the Loxosceles devia spider on breast cancer cells. Experimentally, the venom showed potential selective cytotoxicity, significantly disrupting and killing MDA-MB-231 breast cancer cells, consistent with the pathway of necrosis, while having a more modest impact on non-cancerous MCF10A cells, which is consistent with apoptosis.
Methods
To understand this selectivity, computational models of healthy and cancerous phospholipid membranes were created. Simulations then analyzed the interaction between these membranes and a key venom component, Phospholipase D, while accounting for radiation-induced changes. Two molecular mechanics force fields (MM+ and OPLS) were used. Both revealed a clear differential interaction. Using MM+, binding to cancerous bilayers was far more stable than to healthy ones. OPLS also showed a distinct energetic bias.
Results
The preliminary results suggest the strongest effect on cancer cells was observed in cell viability studies with 10 ug/mL and 40 kGy gamma-irradiated venom. The computational results indicate that venom components interact more strongly with cancer cells, possibly producing a thermodynamic destabilization starting with the cell membrane-venom interaction.
Conclusions
This research suggests a differential venom mechanism between normal and cancer breast cells, and highlights its potential as a basis for novel cancer therapies. Future work will investigate membrane topography and test other cancer cell types.