Silva-Carvalho Amandda Évelin, Oliveira Nakaly Natiely de, Machado Julia Viana Lafetá, Moreira Daniel Carneiro, Brand Guilherme Dotto, Leite José Roberto S A, Plácido Alexandra, Eaton Peter, Saldanha-Araujo Felipe
Laboratory of Hematology and Stem Cells (LHCT), Faculty of Health Sciences, University of Brasilia, Campus Darcy Ribeiro SN, Brasilia 70910-900, Brazil.
Research Center in Morphology and Applied Immunology, NuPMIA, Faculty of Medicine, University of Brasilia, Campus Darcy Ribeiro SN, Brasilia 70910-900, Brazil.
Pharmaceutics. 2023 Jul 1;15(7):1864. doi: 10.3390/pharmaceutics15071864.
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.
两栖动物分泌物已被广泛研究用于生物活性分子的生产。蝾螈素-I是一种抗氧化肽，从火蝾螈的皮肤分泌物中分离出来，对小胶质细胞或红细胞没有毒性。重要的是，抗氧化剂的施用可能构成一种适当的癌症治疗方法。在此，为了更好地表征蝾螈素-I的治疗潜力，我们以人白血病细胞系HL-60作为癌症模型，研究了这种抗氧化肽是否也具有抗癌活性。蝾螈素-I处理导致HL-60增殖显著降低，并伴有细胞周期停滞。此外，肽诱导的细胞死亡表现为HL-60细胞中乳酸脱氢酶释放显著增加。蝾螈素-I施加的细胞毒性可能与焦亡有关，因为肽处理后HL-60细胞显示出线粒体膜电位丧失和炎性小体成分的过度表达。这是蝾螈素-I肽抗癌潜力的首次证明。这些结果很重要，因为它们为癌症治疗领域提供了相关见解，并允许以蝾螈素-I为模板设计未来的生物活性分子。
