Tese
Relação estrutura-atividade do peptídeo sintético Lunatina-1 e seus derivados na citotoxicidade de diferentes linhagens celulares
Fecha
2018-08-17Autor
Kamila de Sousa Gomes
Institución
Resumen
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.