Relação estrutura-atividade do peptídeo sintético Lunatina-1 e seus derivados na citotoxicidade de diferentes linhagens celulares

Abstract

Lunatin-1 is a 13mer peptide isolated from the peruvian scorpion Hadruroides lunatus venom. In this study, the synthetic peptide exhibited activity against different tumor cell lines, such as HL60, MDA-MB-231 e MCF-7. In HL60 cells, a promyelocytic leukemia cell line, was observed that Lunatin-1 induced apoptosis by extrinsic and intrinsic pathways, due to activation of caspases 3, 8 and 9. We also observed a significant increase in ROS production and mitochondrial membrane potential loss. Morphological changes such as nuclear condensation and fragmentation, DNA fragmentation, and phosphatidylserine exposure were also observed. In addition, Lunatin-1 peptide was internalized and important amino acids residues were identified by Alanine-Scan. Lunatin-1 also was evaluated in human mammary adenocarcinoma cells, MDA-MB-231 and MCF-7, and your cytotoxicity in the HepG2, HEK-293 and LUHMES cells. In contrast to the HL60 cells, Lunatin-1 induced cell death by permeability changes of plasma membrane in the MDA-MB-231 cells. A new peptide designed from the similarity between the sequences of Lunatin-1 and caspase-3, denominated L1C3, also showed antitumor /cytotoxic activity against several cell lines. Internalization studies related to the new peptide were also performed. In conclusion, two peptides were identified, Lunatin-1 and L1C3, with antitumor potential against leukemia and breast cancer, as prototypes for the development of new drugs.