AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model

Autores
Armando, Romina Gabriela; Gomez, Daniel Eduardo; Gomez, Daniel Eduardo
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Limitless replicative potential is one of the hallmarks of cancer that is mainly due to the activity of telomerase. This holoenzyme maintains telomere length, adding TTAGGG repetitions at the end of chromosomes in each cell division. In addition to this function, there are extratelomeric roles of telomerase that are involved in cancer promoting events. It has been demonstrated that TERT, the catalytic component of telomerase, acts as a transcriptional modulator in many signaling pathways. Taking into account this evidence and our experience on the study of azidothymidine (AZT) as an inhibitor of telomerase activity, the present study analyzes the effect of AZT on some telomeric and extratelomeric activities. To carry out the present study, we evaluated the transcription of genes that are modulated by the Wnt/β-catenin pathway, such as c-Myc and cyclin-D1 (Cyc-D1) and cell processes related with their expression, such as, proliferation, modifications of the actin cytoskeleton, cell migration and cell cycle in a mammary carcinoma cell line (F3II). Results obtained after treatment with AZT (600 µM) for 15 passages confirmed the inhibitory effect on telomerase. Regarding extratelomeric activities, our results showed a decrease of 64, 38 and 25% in the transcription of c-Myc, Cyc-D1 and TERT, respectively (p<0.05) after AZT treatment. Furthermore, we found an effect on cell migration, reaching an inhibition of 48% (p<0.05) and a significant passage-dependent increase on cell doubling time during treatment. Finally, we evaluated the effect on cell cycle, obtaining a decline in G0/G1 in AZT-treated cells. These results allow us to postulate that AZT is not only an inhibitor of telomerase activity, but also a potential modulator of extratelomeric processes involved in cancer promotion.
Fil: Armando, Romina Gabriela. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
AZT
C-MYC
CYC-D
TELOMERASE
TERT
CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/46768
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/46768
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma modelArmando, Romina GabrielaGomez, Daniel EduardoGomez, Daniel EduardoAZTC-MYCCYC-DTELOMERASETERTCANCERhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Limitless replicative potential is one of the hallmarks of cancer that is mainly due to the activity of telomerase. This holoenzyme maintains telomere length, adding TTAGGG repetitions at the end of chromosomes in each cell division. In addition to this function, there are extratelomeric roles of telomerase that are involved in cancer promoting events. It has been demonstrated that TERT, the catalytic component of telomerase, acts as a transcriptional modulator in many signaling pathways. Taking into account this evidence and our experience on the study of azidothymidine (AZT) as an inhibitor of telomerase activity, the present study analyzes the effect of AZT on some telomeric and extratelomeric activities. To carry out the present study, we evaluated the transcription of genes that are modulated by the Wnt/β-catenin pathway, such as c-Myc and cyclin-D1 (Cyc-D1) and cell processes related with their expression, such as, proliferation, modifications of the actin cytoskeleton, cell migration and cell cycle in a mammary carcinoma cell line (F3II). Results obtained after treatment with AZT (600 µM) for 15 passages confirmed the inhibitory effect on telomerase. Regarding extratelomeric activities, our results showed a decrease of 64, 38 and 25% in the transcription of c-Myc, Cyc-D1 and TERT, respectively (p<0.05) after AZT treatment. Furthermore, we found an effect on cell migration, reaching an inhibition of 48% (p<0.05) and a significant passage-dependent increase on cell doubling time during treatment. Finally, we evaluated the effect on cell cycle, obtaining a decline in G0/G1 in AZT-treated cells. These results allow us to postulate that AZT is not only an inhibitor of telomerase activity, but also a potential modulator of extratelomeric processes involved in cancer promotion.Fil: Armando, Romina Gabriela. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaSpandidos Publications2016-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/46768Armando, Romina Gabriela; Gomez, Daniel Eduardo; Gomez, Daniel Eduardo; AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model; Spandidos Publications; Oncology Reports; 36; 5; 11-2016; 2731-27361021-335XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3892/or.2016.5094info:eu-repo/semantics/altIdentifier/url/https://www.spandidos-publications.com/or/36/5/2731info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:31:32Zoai:ri.conicet.gov.ar:11336/46768instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:31:32.997CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
title AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
spellingShingle AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
Armando, Romina Gabriela
AZT
C-MYC
CYC-D
TELOMERASE
TERT
CANCER
title_short AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
title_full AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
title_fullStr AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
title_full_unstemmed AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
title_sort AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
dc.creator.none.fl_str_mv Armando, Romina Gabriela
Gomez, Daniel Eduardo
Gomez, Daniel Eduardo
author Armando, Romina Gabriela
author_facet Armando, Romina Gabriela
Gomez, Daniel Eduardo
author_role author
author2 Gomez, Daniel Eduardo
author2_role author
dc.subject.none.fl_str_mv AZT
C-MYC
CYC-D
TELOMERASE
TERT
CANCER
topic AZT
C-MYC
CYC-D
TELOMERASE
TERT
CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Limitless replicative potential is one of the hallmarks of cancer that is mainly due to the activity of telomerase. This holoenzyme maintains telomere length, adding TTAGGG repetitions at the end of chromosomes in each cell division. In addition to this function, there are extratelomeric roles of telomerase that are involved in cancer promoting events. It has been demonstrated that TERT, the catalytic component of telomerase, acts as a transcriptional modulator in many signaling pathways. Taking into account this evidence and our experience on the study of azidothymidine (AZT) as an inhibitor of telomerase activity, the present study analyzes the effect of AZT on some telomeric and extratelomeric activities. To carry out the present study, we evaluated the transcription of genes that are modulated by the Wnt/β-catenin pathway, such as c-Myc and cyclin-D1 (Cyc-D1) and cell processes related with their expression, such as, proliferation, modifications of the actin cytoskeleton, cell migration and cell cycle in a mammary carcinoma cell line (F3II). Results obtained after treatment with AZT (600 µM) for 15 passages confirmed the inhibitory effect on telomerase. Regarding extratelomeric activities, our results showed a decrease of 64, 38 and 25% in the transcription of c-Myc, Cyc-D1 and TERT, respectively (p<0.05) after AZT treatment. Furthermore, we found an effect on cell migration, reaching an inhibition of 48% (p<0.05) and a significant passage-dependent increase on cell doubling time during treatment. Finally, we evaluated the effect on cell cycle, obtaining a decline in G0/G1 in AZT-treated cells. These results allow us to postulate that AZT is not only an inhibitor of telomerase activity, but also a potential modulator of extratelomeric processes involved in cancer promotion.
Fil: Armando, Romina Gabriela. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Limitless replicative potential is one of the hallmarks of cancer that is mainly due to the activity of telomerase. This holoenzyme maintains telomere length, adding TTAGGG repetitions at the end of chromosomes in each cell division. In addition to this function, there are extratelomeric roles of telomerase that are involved in cancer promoting events. It has been demonstrated that TERT, the catalytic component of telomerase, acts as a transcriptional modulator in many signaling pathways. Taking into account this evidence and our experience on the study of azidothymidine (AZT) as an inhibitor of telomerase activity, the present study analyzes the effect of AZT on some telomeric and extratelomeric activities. To carry out the present study, we evaluated the transcription of genes that are modulated by the Wnt/β-catenin pathway, such as c-Myc and cyclin-D1 (Cyc-D1) and cell processes related with their expression, such as, proliferation, modifications of the actin cytoskeleton, cell migration and cell cycle in a mammary carcinoma cell line (F3II). Results obtained after treatment with AZT (600 µM) for 15 passages confirmed the inhibitory effect on telomerase. Regarding extratelomeric activities, our results showed a decrease of 64, 38 and 25% in the transcription of c-Myc, Cyc-D1 and TERT, respectively (p<0.05) after AZT treatment. Furthermore, we found an effect on cell migration, reaching an inhibition of 48% (p<0.05) and a significant passage-dependent increase on cell doubling time during treatment. Finally, we evaluated the effect on cell cycle, obtaining a decline in G0/G1 in AZT-treated cells. These results allow us to postulate that AZT is not only an inhibitor of telomerase activity, but also a potential modulator of extratelomeric processes involved in cancer promotion.
publishDate 2016
dc.date.none.fl_str_mv 2016-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/46768
Armando, Romina Gabriela; Gomez, Daniel Eduardo; Gomez, Daniel Eduardo; AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model; Spandidos Publications; Oncology Reports; 36; 5; 11-2016; 2731-2736
1021-335X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/46768
identifier_str_mv Armando, Romina Gabriela; Gomez, Daniel Eduardo; Gomez, Daniel Eduardo; AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model; Spandidos Publications; Oncology Reports; 36; 5; 11-2016; 2731-2736
1021-335X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3892/or.2016.5094
info:eu-repo/semantics/altIdentifier/url/https://www.spandidos-publications.com/or/36/5/2731
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Spandidos Publications
publisher.none.fl_str_mv Spandidos Publications
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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