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Master's Dissertation
DOI
Document
Author
Full name
Jessica Liliane Paz
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Bydlowski, Sergio Paulo (President)
Caldini, Elia Tamaso Espin Garcia
Isaac, Cesar
Rodrigues, Alessandro
Title in Portuguese
Características da toxicidade promovida por oxisteróis em células-tronco mesenquimais derivadas da medula óssea de pacientes com leucemia mieloide aguda
Keywords in Portuguese
7-Cetocolesterol
Apoptose
Autofagia
Células-tronco mesenquimais
Leucemia mieloide aguda
Medula óssea
Morte celular
Oxisteróis
ROS
Abstract in Portuguese
A leucemia mieloide aguda (LMA) é uma neoplasia que afeta a maturação das células-tronco hematopoiéticas (CTH), comprometendo a produção dos componentes saudáveis da medula óssea. A LMA acomete pessoas de todas as idades e a sobrevida de indivíduos portadores da doença ainda é baixa. Vários estudos relatam a interação das células-tronco mesenquimais (CTM) na regulação e manutenção das CTH, onde podem secretar mediadores no microambiente que estão envolvidos na malignidade dos tumores hematológicos. Desse modo, são imprescindíveis novas formas de adjuvantes terapêuticos no combate ao câncer. Como forma de tratamento adjuvante, estudos demonstraram que substâncias como oxisteróis, que são compostos oxidados do colesterol, tem a capacidade de induzir morte celular em diversas linhagens celulares. Portanto, este trabalho relata as características de morte celular dos oxisteróis 7-cetocolesterol (7-KC), colestane-3Beta-5Alfa-6Beta-triol (Triol), 3,5 colestane-7-ona (Colestona), 3Alfa-5Beta-6Alfa-colestane-3,6-diol (Diol), acetato de colesterol (Acetato), 7-oxocolesterol-5-em-3-beta-il-acetato (7-oxo), 5Beta-6Beta epoxicolesterol (Epoxi) em CTM de indivíduos portadores de LMA. Os resultados indicaram que os oxisteróis 7-KC e Triol tiveram efeitos citotóxicos promovendo a morte celular. O 7-KC foi avaliado em relação aos mecanismos de sua citotoxicidade, gerando aumento de ROS, apoptose e autofagia de modo dose-dependente, o que explica pelo menos em parte, seu efeito citotóxico. Desse modo, o 7-KC apresenta potencial efeito como adjuvante terapêutico
Title in English
Characteristics of toxicity promoted by oxysterols in mesenchymal stem cells derived from bone marrow of patients with acute myeloid leukemia
Keywords in English
7-Ketocholesterol
Acute myeloid leukemia
Apoptosis
Autophagy
Bone marrow
Cell death
Mesenchymal stem cells
Oxysterol
ROS
Abstract in English
Acute myeloid leukemia (AML) is a neoplasm that affects maturation of hematopoietic stem cells (HSC), compromising the production of healthy bone marrow components. AML affects people of all ages and the survival rates of individuals with the disease are still low. Several studies report the interaction of mesenchymal stem cells (MSC) in the regulation and maintenance of HSC. MSC can secrete mediators in the microenvironment that are involved in the malignancy of hematological tumors. Thus, new forms of therapeutic adjuvants in the fight against cancer are essential. As an adjuvant treatment, studies have shown that substances such as oxisterols, which are oxidized compounds of cholesterol, have the ability to induce cell death in several cell lines. Therefore, this paper reports the cell death characteristics of oxisterols. 7-ketocholesterol (7-KC), cholestane-3Beta-5Alpha-6Beta-triol (Triol), 3,5-cholestane-7-one (Cholestone), 3Alpha-5Beta -6Alpha-cholestane-3,6-diol (Diol), cholesteryl acetate (Acetate), 7-oxocolesterol-5-em-3-beta-yl-acetate (7-oxo), 5Beta-6Beta epoxycholesterol (Epoxy) in MSC of individuals with AML. The results indicated that 7-KC and Triol oxysterols had cytotoxic effects promoting cell death. Further, 7-KC was evaluated in relation to the mechanisms of cytotoxicity. It led to ROS increase, apoptosis and autophagy in a dose-dependent manner, which explains, at least in part, the observed cytotoxic effect. Thus, 7-KC is a potential therapeutic adjuvant in the treatment of this disease
 
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Publishing Date
2019-10-16
 
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