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Doctoral Thesis
DOI
10.11606/T.88.2009.tde-04092009-142533
Document
Author
Full name
José Emilio Fehr Pereira Lopes
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2009
Supervisor
Committee
Gomes, Ligia Ferreira (President)
Fernandes, Luiz Claudio
Espreafico, Enilza Maria
Jasiulionis, Miriam Galvonas
Souza, Cacilda da Silva
Title in Portuguese
Efeito antiangiogênico do metil jasmonato, puro ou nanocarreado, um novo mecanismo para sua ação antineoplásica e antimetastática
Keywords in Portuguese
Angiogênese
Antiangiogênese
Cancer
Metil Jasmonato
Nanocarreadores
Abstract in Portuguese
Moléculas de origem vegetal foram há muito testadas como fonte de drogas antineoplásicas com sucesso promissor. Este trabalho trata dos efeitos antiangiogênicos do Metil Jasmonato. Este derivado hidrofóbico do ácido jasmônico foi demonstrado anteriormente como um agente de dano seletivo para a mitocôndria de células neoplásicas. In vitro, o Metil Jasmonato 1-10 mM promoveu a morte celular de células endoteliais humanas de cordão umbilical (HUVEC) e de melanoma murino (B16 -F10), enquanto concentrações micromolares foram inócuas. A inclusão do Metil Jasmonato em liposomos de fosfatidilcolina e em um nanocarreador hidrofílico baseado em açúcar mostrou efeitos diferenciais sobre a citotoxicidade. A interrupção do ciclo celular foi observada em concentrações citotóxicas, enquanto a diminuição na produção de VEGF e algum grau de autofagia foram sugeridos em concentrações micromolares. In vivo, Metil Jasmonato 1-10mM foi francamente tóxico, e reduziu a densidade de vasos em membranas corioalantóicas de embrião de galinha (CAM). Entretanto, concentrações entre 1-10 ?M produziram um efeito complexo. Ocorreu aumento no brotamento capilar, mas os novos vasos apresentaram-se frágeis e menos organizados que os controles correspondentes. Sugere-se que, além da toxicidade direta, a ação do Metil Jasmonato sobre a angiogênese seja relevante para seu efeito antineoplásico.
Title in English
Antiangiogenic effect of Methyl Jasmonate, pure or withing a nanocarrier: a new mechanism for its antineoplasic and antimetastatic action
Keywords in English
antiangiogenesis
CAM model
endothelial cell culture
HUVEC
Methyl Jasmonate
Abstract in English
Molecular plant components have long been tested as sources for antineoplasic drugs with promising success. The present work deals with the anti-angiogenic effects of Methyl Jasmonate. This hydrophobic Jasmonate derivative was previously demonstrated to selectively damage the mitochondria of cancer cells. In vitro, 1-10 mM Methyl Jasmonate induced the cell death of the human umbilical vein endothelial cells (HUVEC) and the Murine melanoma cells (B16-F10), while micromolar concentrations were ineffective. Methyl Jasmonate inclusion in phosphatidylcholine liposomes and in an hydrophilic sugar based nanocarrier presented differential effects upon citotoxicity. Cell cycle arrest was observed in citotoxic concentrations, while VEGF withdrawn and some autophagy was suggested in the micromolar range. In vivo, 1-10mM concentrations were explicitly toxic and reduced the vessel density of the Chorioallantoic Membrane of the Chicken Embryo (CAM). However, 1-10 ?M concentrations produced a complex effect. There was increased capillary budding, but the new vessels were leakier and less organized than corresponding controls. It is suggested that not only direct toxicity, but also the drug effects upon angiogenesis are relevant to the antineoplasic effects of Methyl Jasmonate.
 
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Publishing Date
2009-11-13
 
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