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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2015.tde-08122015-194807
Document
Author
Full name
Bianca Rocha Sales
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Santelli, Glaucia Maria Machado (President)
Oliveira, Sergio Ferreira de
Silva Junior, Pedro Ismael da
Title in Portuguese
Potencial antitumoral do composto 7-epi-clusianona em linhagens celulares de câncer de mama humano cultivadas como monocamadas e esferoides.
Keywords in Portuguese
7-epi-clusianona
Garcinia brasiliensis
Bloqueio no ciclo celular
Células de tumor de mama humano
Cultura tridimensional
Produtos naturais anticâncer
Senescência celular
Abstract in Portuguese
A biodiversidade de plantas brasileiras é uma fonte muito rica de moléculas bioativas, dentro da proposta da busca por novas drogas antitumorais, avaliamos neste estudo o potencial antiproliferativo do composto 7-epi-clusianona. Foram utilizadas duas linhagens celulares derivadas de tumor de mama humana, Hs 578T e MCF-7, cultivadas em monocamada e como esferoides. O IC50 após 48 horas de tratamento das células é de 20 μM para Hs 578T e 6 μM para MCF-7. A análise do ciclo celular mostrou que o composto é capaz de reter as células em fase G1/G0 em ambas as linhagens em 2D, mas não em 3D. O composto é capaz de induzir as células a senescência celular, como mostrado pelo ensaio de detecção de β-galactosidase. Esses dados indicam que o composto 7-epi-clusianona é uma molécula promissora, que demonstrou potencial antitumoral em células de tumor de mama. A cultura tridimensional se mostrou mais resistente ao tratamento com 7-epi-clusianona, portanto estudos mais abrangentes são necessários para melhor entendimento dos efeitos do composto sobre esse tipo de cultura.
Title in English
Antitumoral potential of 7-epi-clusianone in human breast cancer cell lines cultured in monolayer and as spheroids.
Keywords in English
7-epi-clusianone
Garcinia brasiliensis
Cell cycle arrest
Cellular senescence
Human breast cancer cell lines
Natural products anticancer
Three-dimensional culture
Abstract in English
Brazilian flora is considered one of the most diverse in the world and natural products are some of the important sources of new antitumoral compounds. The aim of this study was to evaluate the antiproliferative potential of 7-epi-clusianone. Two cell lines derived from human breast tumor were used, Hs 578T and MCF-7, cultured in monolayer and as spheroids. The IC50 after 48 hours of treatment is 20 μM to Hs 578T cells and 6 μM to MCF-7 cells. Cell cycle analysis showed induction of cell cycle arrest in G1/S phase in cells cultured in monolayers, but not in spheroids. The amount of cells in senescence after the treatment with 7-epi-clusianone is higher than the control group, as seen by the senescence β-galactosidase staining assay. These data suggest that 7-epi-clusianone is a promising molecule against breast cancer cells. We show that 3D culture was more resistant to treatment than 2D culture, therefore more comprehensive studies are needed to better understand the effects of 7-epi-clusianone on this kind of culture.
 
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Publishing Date
2015-12-08
 
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