The Peptide Salamandrin-I Modulates Components Involved in Pyroptosis and Induces Cell Death in Human Leukemia Cell Line HL-60
Amandda Évelin Silva-Carvalho,
Nakaly Natiely de Oliveira,
Julia Viana Lafetá Machado,
Daniel Carneiro Moreira,
Guilherme Dotto Brand,
José Roberto S. A. Leite,
Alexandra Plácido,
Peter Eaton,
Felipe Saldanha-Araujo
Affiliations
Amandda Évelin Silva-Carvalho
Laboratory of Hematology and Stem Cells (LHCT), Faculty of Health Sciences, University of Brasilia, Campus Darcy Ribeiro SN, Brasilia 70910-900, Brazil
Nakaly Natiely de Oliveira
Laboratory of Hematology and Stem Cells (LHCT), Faculty of Health Sciences, University of Brasilia, Campus Darcy Ribeiro SN, Brasilia 70910-900, Brazil
Julia Viana Lafetá Machado
Laboratory of Hematology and Stem Cells (LHCT), Faculty of Health Sciences, University of Brasilia, Campus Darcy Ribeiro SN, Brasilia 70910-900, Brazil
Daniel Carneiro Moreira
Research Center in Morphology and Applied Immunology, NuPMIA, Faculty of Medicine, University of Brasilia, Campus Darcy Ribeiro SN, Brasilia 70910-900, Brazil
Guilherme Dotto Brand
Institute of Chemistry, University of Brasilia, Campus Darcy Ribeiro SN, Brasilia 70910-900, Brazil
José Roberto S. A. Leite
Research Center in Morphology and Applied Immunology, NuPMIA, Faculty of Medicine, University of Brasilia, Campus Darcy Ribeiro SN, Brasilia 70910-900, Brazil
Alexandra Plácido
LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal
Peter Eaton
The Bridge, School of Chemistry, University of Lincoln, Lincoln LN6 7TS, UK
Felipe Saldanha-Araujo
Laboratory of Hematology and Stem Cells (LHCT), Faculty of Health Sciences, University of Brasilia, Campus Darcy Ribeiro SN, Brasilia 70910-900, Brazil
Amphibian secretions have been extensively investigated for the production of bioactive molecules. Salamandrin-I is an antioxidant peptide, isolated from the skin secretion of the fire salamander, that has induced no toxicity in microglia or erythrocytes. Importantly, the administration of antioxidants may constitute an adequate therapeutic approach to cancer treatment. Here, with the purpose of better characterizing the therapeutic potential of salamandrin-I, we investigated whether this antioxidant peptide also exerts anticancer activity, using the human leukemia cell line HL-60 as a cancer model. Salamandrin-I treatment induced a significant reduction in HL-60 proliferation, which was accompanied by cell cycle arrest. Furthermore, the peptide-induced cell death showed a significant increase in the LDH release in HL-60 cells. The cellular toxicity exerted by salamandrin-I is possibly related to pyroptosis, since the HL-60 cells showed loss of mitochondrial membrane potential and hyperexpression of inflammasome components following the peptide treatment. This is the first demonstration of the anticancer potential of the salamandrin-I peptide. Such results are important, as they offer relevant insights into the field of cancer therapy and allow the design of future bioactive molecules using salamandrin-I as a template.
