Avaliação da interação molecular de 1,4 naftoquinona em modelos de membrana celular utilizando filmes de Langmuir

• Ano de defesa: 2014
• Autor(a) principal: Hussein, Nadia [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: Thin films; Quinone; Membrane models; Surfaces; Monolayers; Filmes finos; Quinonas; Modelos de membrana; Superfícies; Monocamadas
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=1355715; http://repositorio.unifesp.br/handle/11600/47953

Cancer is a disease characterized by the uncontrolled multiplication and spread of abnormal forms of cells. In order to treat cancer, anticancer drugs were used, which are natural or organosynthetic compounds that act against the development of cancer cells and tumor growth. In this group, we can include 1,4- naphthoquinone, which is present in various chemotherapeutics. It is a derivative of vitamin K, and a potent inhibitor of cell growth and tumor angiogenesis. Thus, this study aims to understand at the molecular level the interaction between this drug and cell membrane by means of simplified models of cell membrane (Langmuir monolayers formed by lipids). For this purpose, we performed measurements of surface tensiometry, curved surface pressure - area and infrared spectroscopy. For that, we employed the phospholipid DPPC (dipalmitoylphosphatidylcholine) for the formation of lipid monolayers (Langmuir films) which mimicked a healthy cell membrane, and DPPS (dipalmitoylphosphatidyl serine), representing cancerous membranes. Rabbit aorta endothelialcell cultures for healthy and tumorigenic cells were also employed. Phospholipids were spread on aqueous solutions, and surface pressure – area isotherms and infrared spectra were obtained. After that, different amounts of 1,4- naphthoquinone were added to the lipid monolayer and new isotherms and spectra were obtained . Similar procedures were performed with cell cultures. Three phenomena were observed due to the interaction between the monolayer and the drug: 1 ) the isotherms were shifted to smaller molecular areas, 2) 1,4- naphthoquinone increased the compressibility of the monolayer , causing a disruption in the organization of the film, which was confirmed later by infrared spectroscopy, and 3) the phase transitions has not been well defined in the surface pressure-area isotherms, suggesting a non-ideal mixture, due to interactions between the drug and the monolayer. For cell cultures, whereas minor changes were observed for cultures representing non-tumorigenic cells after the incorporation of the drug, significant changes were observed for cultures representing tumorigenic cells. Therefore, we conclude that 1,4-naphthoquinone interacts with cell membrane models represented by monolayers of DPPC, DPPS and cell cultures studied with a more expressive interaction with models of tumorigenic cells.