The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers

Autores
Costantino, Valeria Victoria; Mansilla, Sabrina Florencia; Speroni, Juliana; Amaya, Celina; Cuello Carrión, Fernando Darío; Ciocca, Daniel Ramon; Priestap, Horacio A.; Barbieri, M. A.; Gottifredi, Vanesa; Lopez, Luis Alberto
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Sesquiterpene lactones (SLs) are plant-derived compounds that display anti-cancer effects. Some SLs derivatives have a marked killing effect on cancer cells and have therefore reached clinical trials. Little is known regarding the mechanism of action of SLs. We studied the responses of human cancer cells exposed to various concentrations of dehydroleucodine (DhL), a SL of the guaianolide group isolated and purified from Artemisia douglasiana (Besser), a medicinal herb that is commonly used in Argentina. We demonstrate for the first time that treatment of cancer cells with DhL, promotes the accumulation of DNA damage markers such as phosphorylation of ATM and focal organization of cH2AX and 53BP1. This accumulation triggers cell senescence or apoptosis depending on the concentration of the DhL delivered to cells. Transient DhL treatment also induces marked accumulation of senescent cells. Our findings help elucidate the mechanism whereby DhL triggers cell cycle arrest and cell death and provide a basis for further exploration of the effects of DhL in in vivo cancer treatment models.
Fil: Costantino, Valeria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza; Argentina;
Fil: Mansilla, Sabrina Florencia. Fundación Instituto Leloir; Argentina;
Fil: Speroni, Juliana. Fundación Instituto Leloir; Argentina;
Fil: Amaya, Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza; Argentina;
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;
Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;
Fil: Priestap, Horacio A.. Department of Biological Sciences, Florida International University; Estados Unidos;
Fil: Barbieri, M. A.. Department of Biological Sciences, Florida International University; Estados Unidos; Falrchild Tropical Botanic Garden; Estados Unidos;
Fil: Gottifredi, Vanesa. Fundación Instituto Leloir; Argentina;
Fil: Lopez, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza; Argentina;
Materia
DEHYDROLEUCODINE
SENESCENCE
APOPTOSIS
DNA DAMAGE MARKERS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
Atribución-NoComercial-CompartirIgual 2.5 Argentina (CC 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:11336/2248
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/2248
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markersCostantino, Valeria VictoriaMansilla, Sabrina FlorenciaSperoni, JulianaAmaya, CelinaCuello Carrión, Fernando DaríoCiocca, Daniel RamonPriestap, Horacio A.Barbieri, M. A.Gottifredi, VanesaLopez, Luis AlbertoDEHYDROLEUCODINESENESCENCEAPOPTOSISDNA DAMAGE MARKERShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Sesquiterpene lactones (SLs) are plant-derived compounds that display anti-cancer effects. Some SLs derivatives have a marked killing effect on cancer cells and have therefore reached clinical trials. Little is known regarding the mechanism of action of SLs. We studied the responses of human cancer cells exposed to various concentrations of dehydroleucodine (DhL), a SL of the guaianolide group isolated and purified from Artemisia douglasiana (Besser), a medicinal herb that is commonly used in Argentina. We demonstrate for the first time that treatment of cancer cells with DhL, promotes the accumulation of DNA damage markers such as phosphorylation of ATM and focal organization of cH2AX and 53BP1. This accumulation triggers cell senescence or apoptosis depending on the concentration of the DhL delivered to cells. Transient DhL treatment also induces marked accumulation of senescent cells. Our findings help elucidate the mechanism whereby DhL triggers cell cycle arrest and cell death and provide a basis for further exploration of the effects of DhL in in vivo cancer treatment models.Fil: Costantino, Valeria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza; Argentina;Fil: Mansilla, Sabrina Florencia. Fundación Instituto Leloir; Argentina;Fil: Speroni, Juliana. Fundación Instituto Leloir; Argentina;Fil: Amaya, Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza; Argentina;Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;Fil: Priestap, Horacio A.. Department of Biological Sciences, Florida International University; Estados Unidos;Fil: Barbieri, M. A.. Department of Biological Sciences, Florida International University; Estados Unidos; Falrchild Tropical Botanic Garden; Estados Unidos;Fil: Gottifredi, Vanesa. Fundación Instituto Leloir; Argentina;Fil: Lopez, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza; Argentina;Public Library Of Science2013-01-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2248Costantino, Valeria Victoria; Mansilla, Sabrina Florencia; Speroni, Juliana; Amaya, Celina; Cuello Carrión, Fernando Darío; et al.; The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers; Public Library Of Science; Plos One; 8; 1; 14-1-2013; 1-151932-6203enginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0053168info:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053168info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 2.5 Argentina (CC BY-NC-SA 2.5 AR)https://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:13:22Zoai:ri.conicet.gov.ar:11336/2248instacron: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:34982025-09-10 13:13:22.6CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers
title The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers
spellingShingle The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers
Costantino, Valeria Victoria
DEHYDROLEUCODINE
SENESCENCE
APOPTOSIS
DNA DAMAGE MARKERS
title_short The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers
title_full The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers
title_fullStr The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers
title_full_unstemmed The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers
title_sort The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers
dc.creator.none.fl_str_mv Costantino, Valeria Victoria
Mansilla, Sabrina Florencia
Speroni, Juliana
Amaya, Celina
Cuello Carrión, Fernando Darío
Ciocca, Daniel Ramon
Priestap, Horacio A.
Barbieri, M. A.
Gottifredi, Vanesa
Lopez, Luis Alberto
author Costantino, Valeria Victoria
author_facet Costantino, Valeria Victoria
Mansilla, Sabrina Florencia
Speroni, Juliana
Amaya, Celina
Cuello Carrión, Fernando Darío
Ciocca, Daniel Ramon
Priestap, Horacio A.
Barbieri, M. A.
Gottifredi, Vanesa
Lopez, Luis Alberto
author_role author
author2 Mansilla, Sabrina Florencia
Speroni, Juliana
Amaya, Celina
Cuello Carrión, Fernando Darío
Ciocca, Daniel Ramon
Priestap, Horacio A.
Barbieri, M. A.
Gottifredi, Vanesa
Lopez, Luis Alberto
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DEHYDROLEUCODINE
SENESCENCE
APOPTOSIS
DNA DAMAGE MARKERS
topic DEHYDROLEUCODINE
SENESCENCE
APOPTOSIS
DNA DAMAGE MARKERS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Sesquiterpene lactones (SLs) are plant-derived compounds that display anti-cancer effects. Some SLs derivatives have a marked killing effect on cancer cells and have therefore reached clinical trials. Little is known regarding the mechanism of action of SLs. We studied the responses of human cancer cells exposed to various concentrations of dehydroleucodine (DhL), a SL of the guaianolide group isolated and purified from Artemisia douglasiana (Besser), a medicinal herb that is commonly used in Argentina. We demonstrate for the first time that treatment of cancer cells with DhL, promotes the accumulation of DNA damage markers such as phosphorylation of ATM and focal organization of cH2AX and 53BP1. This accumulation triggers cell senescence or apoptosis depending on the concentration of the DhL delivered to cells. Transient DhL treatment also induces marked accumulation of senescent cells. Our findings help elucidate the mechanism whereby DhL triggers cell cycle arrest and cell death and provide a basis for further exploration of the effects of DhL in in vivo cancer treatment models.
Fil: Costantino, Valeria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza; Argentina;
Fil: Mansilla, Sabrina Florencia. Fundación Instituto Leloir; Argentina;
Fil: Speroni, Juliana. Fundación Instituto Leloir; Argentina;
Fil: Amaya, Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza; Argentina;
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;
Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina;
Fil: Priestap, Horacio A.. Department of Biological Sciences, Florida International University; Estados Unidos;
Fil: Barbieri, M. A.. Department of Biological Sciences, Florida International University; Estados Unidos; Falrchild Tropical Botanic Garden; Estados Unidos;
Fil: Gottifredi, Vanesa. Fundación Instituto Leloir; Argentina;
Fil: Lopez, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histología y Embriología de Mendoza; Argentina;
description Sesquiterpene lactones (SLs) are plant-derived compounds that display anti-cancer effects. Some SLs derivatives have a marked killing effect on cancer cells and have therefore reached clinical trials. Little is known regarding the mechanism of action of SLs. We studied the responses of human cancer cells exposed to various concentrations of dehydroleucodine (DhL), a SL of the guaianolide group isolated and purified from Artemisia douglasiana (Besser), a medicinal herb that is commonly used in Argentina. We demonstrate for the first time that treatment of cancer cells with DhL, promotes the accumulation of DNA damage markers such as phosphorylation of ATM and focal organization of cH2AX and 53BP1. This accumulation triggers cell senescence or apoptosis depending on the concentration of the DhL delivered to cells. Transient DhL treatment also induces marked accumulation of senescent cells. Our findings help elucidate the mechanism whereby DhL triggers cell cycle arrest and cell death and provide a basis for further exploration of the effects of DhL in in vivo cancer treatment models.
publishDate 2013
dc.date.none.fl_str_mv 2013-01-14
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/11336/2248
Costantino, Valeria Victoria; Mansilla, Sabrina Florencia; Speroni, Juliana; Amaya, Celina; Cuello Carrión, Fernando Darío; et al.; The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers; Public Library Of Science; Plos One; 8; 1; 14-1-2013; 1-15
1932-6203
url http://hdl.handle.net/11336/2248
identifier_str_mv Costantino, Valeria Victoria; Mansilla, Sabrina Florencia; Speroni, Juliana; Amaya, Celina; Cuello Carrión, Fernando Darío; et al.; The sesquiterpene lactone dehydroleucodine triggers senescence and apoptosis in association with accumulation of DNA damage markers; Public Library Of Science; Plos One; 8; 1; 14-1-2013; 1-15
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0053168
info:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053168
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Atribución-NoComercial-CompartirIgual 2.5 Argentina (CC BY-NC-SA 2.5 AR)
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv Atribución-NoComercial-CompartirIgual 2.5 Argentina (CC BY-NC-SA 2.5 AR)
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 Public Library Of Science
publisher.none.fl_str_mv Public Library Of Science
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 12.993085

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