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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2018.tde-15022018-101629
Document
Author
Full name
Anali Del Milagro Bernabe Garnique
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Santelli, Glaucia Maria Machado (President)
Colquhoun, Alison
França, Carolina Nunes
Niero, Evandro Luís de Oliveira
Title in Portuguese
Efeito de inibidores de telomerase sobre células tumorais de pulmão humano e sobre células imortalizadas com hTERT.
Keywords in Portuguese
Adesão celular
inibidores de telomerase
senescência celular
telomerase
telômero
Abstract in Portuguese
O telômero é uma sequência repetitiva da dupla cadeia do DNA que protege as pontas dos cromossomos. Seu comprimento é mantido pela telomerase, cuja expressão ocorre em células de câncer, mas não em células somáticas. A célula apresenta um número definido de divisões antes do telômero sofrer erosão. A quebra do DNA ativa a p53, supressor tumoral que induz senescência e respostas de pontos de checagem. O desenvolvimento de inibidores de telomerase tem importância clínica para o câncer. Estudamos os efeitos dos inibidores de telomerase. Duas linhagens celulares LC-HK2 (NSCLC) e hTERT RPE-1 foram tratadas com os inibidores TMPyP4 (5µM) e Thymoquinone (10 e 40 µM) durante 72 e 120 h. TMPyP4 aumentou a porcentagem de células com dano na membrana, induziu mudança na morfologia da célula e diminuiu a expressão do mRNA da vimentina e vinculina. Thymoquinone aumentou a frequência de células senescentes, células com dano na membrana e induziu morte celular. Ambos os inibidores diminuíram a atividade da telomerase, afetando a proliferação e induzindo morte celular.
Title in English
Effect of telomerase inhibitors on human lung tumor cells and on cells immortalized with hTERT.
Keywords in English
Cell adhesion
cell senescence
telomerase
telomerase inhibitors
telomere
Abstract in English
The telomere is a repetitive double-strand sequence of DNA that protects the chromosomes ends. Its length is maintained by telomerase, whose expression occurs in cancer cells, but not in somatic cells. The cell has a defined number of divisions before the telomere undergoes erosion. DNA break activates p53, tumor suppressor and induces senescence and checkpoint responses. The development of telomerase inhibitors is of clinical importance for cancer. We studied the effects of telomerase inhibitors. Two cell lines LC-HK2 (NSCLC) and hTERT RPE-1 were treated with inhibitors TMPyP4 (5 M) and Thymoquinone (10 and 40 M) for 72 and 120 h. TMPyP4 increased the percentage of cells with membrane damage, induced change in cell morphology, and decreased mRNA expression of vimentin and vinculin. Thymoquinone increased the frequency of senescent cells, cells with membrane damage and induced cell death. Both inhibitors decreased telomerase activity, affecting proliferation and inducing cell death.
 
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Release Date
2020-02-15
Publishing Date
2018-10-25
 
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