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Master's Dissertation
DOI
10.11606/D.42.2010.tde-16122010-140400
Document
Author
Full name
Raquel Bernardeth de Almeida
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Santelli, Glaucia Maria Machado (President)
Chavez, Victor Elias Arana
Ribeiro, Alberto Augusto Gonçalves de Freitas Castro
Title in Portuguese
Efeitos da inibição de Aurora A sobre a proliferação e fenótipo de células derivadas de hepatocarcinoma humano.
Keywords in Portuguese
Aberrações nucleares
Apoptose
Aurora A
Carcinoma
Células cultivadas de tumor
Ciclo celular
Citoesqueleto
Fenótipos
Hepatocarcinoma
Proliferação celular
Abstract in Portuguese
Hepatocarcinoma (HCC) é o mais comum tumor maligno primário do fígado. Aurora A é importante durante o ciclo celular, atuando na maturação centrossômica e sua separação, entrada em mitose, montagem de fuso bipolar, alinhamento dos cromossomos na placa metafásica e citocinese. Expressão alterada de Aurora A tem sido associada com o desenvolvimento do tumor e sua superexpressão ocorre em 60% dos HCCs. Inibidores de Aurora quinases têm sido desenvolvidos como drogas antitumorais. 4(4`-Benzamidoanilina)-6,7dimetoxiquizanoline, BADIM, é um recém desenvolvido inibidor da Aurora. Nosso estudo investigou os efeitos de BADIM na linhagem celular HepG2, derivada de HCC, quando tratada com 300, 600 e 1200nm de BADIM por 24 e 48h. Observamos inibição de proliferação, aumento de células tetraplóides, binucleadas e gigantes, bloqueio em G2/M do ciclo celular, alterações nos microtúbulos, mitoses atípicas e apoptose. Por conseguinte, este inibidor é um agente promissor para estudos em HCC, pois atua em pontos críticos relacionados com o processo de tumorigênese.
Title in English
A inhibition effects in proliferation and morphology in cells derivated of Hepatocellular Carcinoma.
Keywords in English
Apoptosis
Aurora A
carcinoma
Cell cycle
Cell proliferation
Cytoskeleton
Hepatocellular carcinoma
Nuclear aberrations
Phenotypes
Tumor cells grown
Abstract in English
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of liver. Aurora A is important during cell cycle, including centrosome maturation and separation, mitotic entry, bipolar-spindle assembly, chromosome alignment on metaphase plate and cytokinesis. Altered expression of Aurora A has been associated with tumor development and its overexpression occurs in 60% of HCC. Aurora kinases inhibitors have been developed as antitumoral drugs. 4(4`-Benzamidoanilino)-6,7-dimethoxiquizanolina, BADIM, is a new Aurora inhibitor. Our study aimed investigates the BADIM effects on HepG2 cell line, derivates of HCC, when treated in 300, 600 and 1200nM for 24 and 48h. We observed inhibition of cell proliferation, increase of tetraploids, binucleated and giant cells, arrest in G2/M cell cycle, microtubules alterations, aberrant cell divisions and apoptosis. Therefore this inhibitor is a promising agent for studies in HCC, since it acts at critical points related to tumorigenesis.
 
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Publishing Date
2011-03-02
 
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