Crotalicidin and NA-CATH-ATRA-1-ATRA-1 peptide-induced membrane disruption in human breast cancer cells

Cationic peptides offer a promising alternative for cancer treatment due to their ability to target cancer cells via standard membrane features, thereby overcoming intratumoral heterogeneity. This study investigates the cytotoxic activity and the membrane-disruptive effects of two snake venom-derived peptides, Crotalicidin (Ctn) and NA-CATH-ATRA-1-ATRA-1 (NA) in human breast cancer cells. Cell viability assays showed that both Ctn and NA significantly diminished the viability of MCF-7 and MDA-MB-231 cells, with NA showing greater potency, as indicated by lower IC50 values of 13.4 μM for MCF-7 and 6.4 μM for MDA-MB-231. Microscopy and flow cytometry revealed size reduction and increased granularity in treated cells. Further analyses indicated that the peptides induced membrane permeabilization, as evidenced by significant propidium iodide uptake, without significantly altering mitochondrial membrane potential. Apoptosis markers such as cleaved caspase-9 and PARP, were not detected by western blot. Additionally, LDH release and confocal microscopic analysis supported the findings of membrane disruption. Finally, infrared spectroscopy (FT-IR) on lipid extracts revealed peptide-membrane interactions, resulting in phase transitions consistent with membrane disruption. These findings highlight the potent cytotoxic effects of Ctn and NA on breast cancer cells and their potential as novel therapeutic agents.

• Autores: Gallego Londoño, Vanessa; Santa González, Gloria Angélica; Giraldo Lorza, Juan Manuel; Rojas López, Mauricio; Manrique Moreno, Marcela María; Wisman, G. Bea A.; Jong, Steven de
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2025
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/46545
• Acceso en línea: https://hdl.handle.net/10495/46545
• Palabra clave: Peptidos; Peptides; Neoplasias de mama; Breast Neoplasms; Citotoxinas; Cytotoxins; Permeabilidad de la Membrana Celular; Cell Membrane Permeability; Snake Venoms - pharmacology; Venenos de serpiente - farmacología; http://id.nlm.nih.gov/mesh/D010455; http://id.nlm.nih.gov/mesh/D001943; http://id.nlm.nih.gov/mesh/D003603; http://id.nlm.nih.gov/mesh/D002463; http://id.nlm.nih.gov/mesh/D012910; ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/4.0/