Título:	Effects of in vitro short- and long-term treatment with telomerase inhibitor in U-251 glioma cells
Autor(es):	Mota, Tales Henrique Andrade da Guimarães, Ana Flavia Reis Carvalho, Amandda Évelin Silva de Araújo, Felipe Saldanha de Lopes, Giselle Pinto de Faria Pittella-Silva, Fabio Rabello, Doralina do Amaral Oliveira, Diego Madureira de
ORCID:	https://orcid.org/0000-0002-6272-6558
Afiliação do autor:	Universidade de Brasília, Faculdade UnB Ceilândia Universidade de Brasília, Faculdade de Ciências da Saúde, Departamento de Farmácia Universidade de Brasília, Faculdade de Ciências da Saúde, Departamento de Farmácia Universidade de Brasília, Faculdade de Ciências da Saúde, Departamento de Farmácia Laboratório de Hemato-oncologia Celular e Molecular, Instituto Nacional do Câncer (INCA) Departamento de Biotecnologia Marinha, Instituto de Estudos do Mar do Almirante Paulo Moreira, IEAPM
Assunto:	Glioma Telomerase Câncer - tratamento
Data de publicação:	2021
Editora:	IOS Press
Referência:	MOTA, Tales Henrique Andrade da et al. Effects of in vitro short- and long-term treatment with telomerase inhibitor in U-251 glioma cells. Tumor Biology, v. 43, p. 327-340, 2021. DOI: 10.3233/TUB-211515. Disponível em: https://content.iospress.com/articles/tumor-biology/tub211515. Acesso em:05 set. 2022.
Abstract:	BACKGROUND: The inhibition of the enzyme telomerase (TERT) has been widely investigated as a new pharmacological approach for cancer treatment, but its real potential and the biochemical consequences are not totally understood. OBJECTIVE: Here, we investigated the effects of the telomerase inhibitor MST-312 on a human glioma cell line after both short- and long-term (290 days) treatments. METHODS: Effects on cell growth, viability, cell cycle, morphology, cell death and genes expression were assessed. RESULTS: We found that short-term treatment promoted cell cycle arrest followed by apoptosis. Importantly, cells with telomerase knock-down revealed that the toxic effects of MST-312 are partially TERT dependent. In contrast, although the long-term treatment decreased cell proliferation at first, it also caused adaptations potentially related to treatment resistance and tumor aggressiveness after long time of exposition. CONCLUSIONS: Despite the short-term effects of telomerase inhibition not being due to telomere erosion, they are at least partially related to the enzyme inhibition, which may represent an important strategy to pave the way for tumor growth control, especially through modulation of the non-canonical functions of telomerase. On the other hand, long-term exposure to the inhibitor had the potential to induce cell adaptations with possible negative clinical implications.
Licença:	© 2021 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0)
DOI:	10.3233/TUB-211515
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