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Master's Dissertation
DOI
https://doi.org/10.11606/D.75.2017.tde-08022017-152244
Document
Author
Full name
Marta Érica Saidel
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2016
Supervisor
Committee
Leitão, Andrei (President)
Porto, André Luiz Meleiro
Thiemann, Otavio Henrique
Title in Portuguese
Ensaios celulares para a determinação da atividade citotóxica de moléculas antineoplásicas
Keywords in Portuguese
câncer de próstata
ensaios celulares
mTOR
MTT
Abstract in Portuguese

A pesquisa de substâncias bioativas apresenta diversas etapas de grande complexidade técnico-científica e envolve uma atividade multidisciplinar. No estudo de antineoplásicos, dentre outros candidatos a fármacos, a determinação do perfil de atividade biológica é um ponto essencial para a determinação da potência, toxidez e o índice de seletividade. Neste projeto, os ensaios in vitro de compostos inibidores de catepsinas serão realizados usando células de câncer de próstata resistentes à quimioterapia (DU 145 e PC-3). Os estudos envolverão análises fenotípicas da resposta celular para determinar a viabilidade e o tipo de perturbação do ciclo celular utilizando técnicas colorimétricas e citometria de fluxo, juntamente com o estudo de sinalização celular PI3K-Akt-mTOR. Os testes de atividade citotóxica serão realizados com as células de fibroblasto de camundongo (Balb-c 3T3). Os resultados levarão a caracterização do tipo de resposta biológica e também da citotoxidez das substâncias de interesse.

Title in English
Cellular assays to determine the cytotoxic activity of anticancer molecules
Keywords in English
cellular assays
mTOR
MTT
prostate câncer
Abstract in English

The search for bioactive substances leads to molecules that need to be qualified throughout many complex steps, involving multidisciplinary activities. For antineoplastic molecules, among other classes of candidate drugs, the determination of the biological activity is the core of the whole process with the aim of determining the potency, toxicity and the selectivity index. In this project, in vitro cell-based bioassays of cathepsin inhibitors are going to be performed using prostate cancer cells resistant to chemotherapy (DU 145 and PC-3). Phenotypic studies are going to be used as end-points to observe the cell viability and the perturbation of the cell cycle by means of colorimetric, flow cytometry, coupled with the study of PI3K-Akt-mTOR signaling pathway. Cytotoxic assays are going to be performed in mouse fibroblasts (Balb-c 3T3). As a result, the biological outcome and the cytotoxic profile of the compounds of interest will be addressed.

 
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Publishing Date
2017-02-09
 
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