Uso de peptídeos antimicrobianos contra o câncer: imunomodulação e mecanismos de morte celular

• Ano de defesa: 2017
• Autor(a) principal: Buri, Marcus Vinicius [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Antimicrobial peptides; Immunomodulation; Cancer; Cell death; Neoplasms; Peptídeos antimicrobianos; Imunomodulação; Câncer; Morte celular; Neoplasias
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5010315; https://repositorio.unifesp.br/handle/11600/50533

Cancer is a heterogeneous disease and new therapies are necessaries to evade chemoresistance. Antimicrobial peptides (AMPs) are defense molecules found in different organisms, with antimicrobial activity, and possible antitumor capacity. Although these AMPs have homology in their sequence and structure, the biological activities are different according to the concentration and cell type. In this study, the results were divided into three sections: the first one demonstrated the immunomodulatory capacity of the gomesin peptide, which led to the increase of hematopoietic stem cells, decreased of myeloid progenitors, activation of macrophages, increase of interleukin 6 and monocyte chemotactic protein. In the second study, the cytotoxic capacity of different AMPs (gomesin, tachyplesin protegrin and polyphemusin) was demonstrated in leukemic cells; KG-1 lineage was the most resistant cell line due to the greater activity of multi drug resistance pumps, higher expression of autophagic genes and lower pro-apoptotic constitutive gene expression. In the third section, we evaluated the different mechanisms of cell death triggered by the AMPs (gomesin, tachyplesin protegrin and polyphemusin) in Hela lineage. Caspases activation occurred by all AMPs tested, but little activation of genes, associated with cell death, was observed. The mechanism of cell death of AMPs involves apoptotic characteristics, with reduction of the mitochondrial membrane potential and mitochondrial swelling with involvement of Ca2+ ion. Additionally, the balance between the activation and inhibition of pro-apoptotic, autophagic, survival and proliferation proteins helped to define the peptide potency. This work elucidates the importance of AMPs studies against cancer because they can modulate the immune system, besides promote cell death. These results can be used as base for development a new potent drug against this disease.