Long-term exposure to MST-312 leads to telomerase reverse transcriptase overexpression in MCF-7 breast cancer cells

Morais, Karollyne Silva; Guimarães, Ana Flávia R.; Ramos, Doralina do Amaral Rabello; Pittella-Silva, Fabio; Oliveira, Diêgo Madureira de

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Campo DC	Valor	Idioma
dc.contributor.author	Morais, Karollyne Silva	-
dc.contributor.author	Guimarães, Ana Flávia R.	-
dc.contributor.author	Ramos, Doralina do Amaral Rabello	-
dc.contributor.author	Pittella-Silva, Fabio	-
dc.contributor.author	Oliveira, Diêgo Madureira de	-
dc.date.accessioned	2022-10-03T13:46:45Z	-
dc.date.available	2022-10-03T13:46:45Z	-
dc.date.issued	2017	-
dc.identifier.citation	MORAIS, Karollyne S. et al. Long-term exposure to MST-312 leads to telomerase reverse transcriptase overexpression in MCF-7 breast cancer cells. Anti-Cancer Drugs, [S.l.], v. 28, n. 7, p 750-756, ago. 2017. DOI: 10.1097/CAD.0000000000000508.	pt_BR
dc.identifier.uri	https://repositorio.unb.br/handle/10482/44949	-
dc.language.iso	Inglês	pt_BR
dc.publisher	Lippincott, Williams & Wilkins	pt_BR
dc.rights	Acesso Restrito	pt_BR
dc.title	Long-term exposure to MST-312 leads to telomerase reverse transcriptase overexpression in MCF-7 breast cancer cells	pt_BR
dc.type	Artigo	pt_BR
dc.subject.keyword	Mamas - câncer	pt_BR
dc.subject.keyword	Câncer - tratamento	pt_BR
dc.subject.keyword	Telomerase	pt_BR
dc.subject.keyword	Medicamentos	pt_BR
dc.identifier.doi	10.1097/CAD.0000000000000508	pt_BR
dc.relation.publisherversion	https://journals.lww.com/anti-cancerdrugs/Fulltext/2017/08000/Long_term_exposure_to_MST_312_leads_to_telomerase.6.aspx	pt_BR
dc.description.abstract1	Telomerase is an enzyme responsible for telomere maintenance in almost all human cancer cells, but generally not expressed in somatic ones. Therefore, antitelomerase therapy is a potentially revolutionary therapeutic strategy, and the antitumor activity of telomerase inhibitors (TI) has been studied extensively recently, mainly for breast cancer. However, the effects expected from treatment with TI will appear only after many cell divisions, but the effects of this long-term approach are unknown. In this work, the consequences of 3120 h exposure of human breast cancer cells to TI MST-312 were investigated. MCF-7 cells were treated with MST-312 at a subtoxic concentration for a long time, and then cell morphology, viability, senescence, and proliferation were analyzed by phase-contrast microscopy, MTT assay, β-galactosidase test, and the trypan blue exclusion assay, respectively. Also, chromosomal stability was evaluated by classical cytogenetic analysis. The average length of telomeres and telomerase reverse transcriptase expression were accessed by real-time PCR and real-time RT-PCR, respectively. The MST-312 showed cytotoxic action and promoted telomere erosion, senescence, and chromosome aberrations, as expected, but in a small proportion. Nevertheless, the proliferation rate of the culture was not affected. As the main effect, the chronic exposure led to cell adaptation by overexpression of telomerase in response to the inhibitor, which is a potential cause of therapeutic failure and may be associated with a poor prognosis. In conclusion, despite the high therapeutic potential of TIs such as MST-312, the molecular outcomes of long-term exposure of tumors on these drugs have to be evaluated when considering their clinical application, especially for breast cancer treatment.	pt_BR
dc.contributor.affiliation	Universidade de Brasília, Faculdade de Ciências da Saúde	pt_BR
dc.contributor.affiliation	Universidade de Brasília, Faculdade de Medicina	pt_BR
dc.contributor.affiliation	Universidade de Brasília, Faculdade UnB Ceilândia	pt_BR
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