Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy

Autores
Gamarra Luques, Carlos Diego; Goyeneche, Alicia A.; Hapon, María Belén; Telleria, Carlos Marcelo
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Advanced ovarian cancer is treated with cytoreductive surgery and combination platinum- and taxane-based chemotherapy. Although most patients have acute clinical response to this strategy, the disease ultimately recurs. In this work we questioned whether the synthetic steroid mifepristone, which as monotherapy inhibits the growth of ovarian cancer cells, is capable of preventing repopulation of ovarian cancer cells if given after a round of lethal cisplatin-paclitaxel combination treatment.Methods: We established an in vitro approach wherein ovarian cancer cells with various sensitivities to cisplatin or paclitaxel were exposed to a round of lethal doses of cisplatin for 1 h plus paclitaxel for 3 h. Thereafter, cells were maintained in media with or without mifepristone, and short- and long-term cytotoxicity was assessed.Results: Four days after treatment the lethality of cisplatin-paclitaxel was evidenced by reduced number of cells, increased hypodiploid DNA content, morphological features of apoptosis, DNA fragmentation, and cleavage of caspase-3, and of its downstream substrate PARP. Short-term presence of mifepristone either enhanced or did not modify such acute lethality. Seven days after receiving cisplatin-paclitaxel, cultures showed signs of relapse with escaping colonies that repopulated the plate in a time-dependent manner. Conversely, cultures exposed to cisplatin-paclitaxel followed by mifepristone not only did not display signs of repopulation following initial chemotherapy, but they also had their clonogenic capacity drastically reduced when compared to cells repopulating after cisplatin-paclitaxel.Conclusions: Cytostatic concentrations of mifepristone after exposure to lethal doses of cisplatin and paclitaxel in combination blocks repopulation of remnant cells surviving and escaping the cytotoxic drugs.
Fil: Gamarra Luques, Carlos Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University Of South Dakota. Sanford School Of Medicine; Estados Unidos
Fil: Goyeneche, Alicia A.. University Of South Dakota. Sanford School Of Medicine; Estados Unidos
Fil: Hapon, María Belén. University Of South Dakota. Sanford School Of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Telleria, Carlos Marcelo. University Of South Dakota. Sanford School Of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Mifepristone
cancer de ovario
apoptosis
ciclo celular
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:11336/81171

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network_name_str CONICET Digital (CONICET)
spelling Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapyGamarra Luques, Carlos DiegoGoyeneche, Alicia A.Hapon, María BelénTelleria, Carlos MarceloMifepristonecancer de ovarioapoptosisciclo celularhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Advanced ovarian cancer is treated with cytoreductive surgery and combination platinum- and taxane-based chemotherapy. Although most patients have acute clinical response to this strategy, the disease ultimately recurs. In this work we questioned whether the synthetic steroid mifepristone, which as monotherapy inhibits the growth of ovarian cancer cells, is capable of preventing repopulation of ovarian cancer cells if given after a round of lethal cisplatin-paclitaxel combination treatment.Methods: We established an in vitro approach wherein ovarian cancer cells with various sensitivities to cisplatin or paclitaxel were exposed to a round of lethal doses of cisplatin for 1 h plus paclitaxel for 3 h. Thereafter, cells were maintained in media with or without mifepristone, and short- and long-term cytotoxicity was assessed.Results: Four days after treatment the lethality of cisplatin-paclitaxel was evidenced by reduced number of cells, increased hypodiploid DNA content, morphological features of apoptosis, DNA fragmentation, and cleavage of caspase-3, and of its downstream substrate PARP. Short-term presence of mifepristone either enhanced or did not modify such acute lethality. Seven days after receiving cisplatin-paclitaxel, cultures showed signs of relapse with escaping colonies that repopulated the plate in a time-dependent manner. Conversely, cultures exposed to cisplatin-paclitaxel followed by mifepristone not only did not display signs of repopulation following initial chemotherapy, but they also had their clonogenic capacity drastically reduced when compared to cells repopulating after cisplatin-paclitaxel.Conclusions: Cytostatic concentrations of mifepristone after exposure to lethal doses of cisplatin and paclitaxel in combination blocks repopulation of remnant cells surviving and escaping the cytotoxic drugs.Fil: Gamarra Luques, Carlos Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University Of South Dakota. Sanford School Of Medicine; Estados UnidosFil: Goyeneche, Alicia A.. University Of South Dakota. Sanford School Of Medicine; Estados UnidosFil: Hapon, María Belén. University Of South Dakota. Sanford School Of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Telleria, Carlos Marcelo. University Of South Dakota. Sanford School Of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaBioMed Central2012-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/81171Gamarra Luques, Carlos Diego; Goyeneche, Alicia A.; Hapon, María Belén; Telleria, Carlos Marcelo; Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy; BioMed Central; BMC Cancer; 12; 5-2012; 1-161471-2407CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-200info:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2407-12-200info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:59Zoai:ri.conicet.gov.ar:11336/81171instacron: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:34982025-09-03 09:59:59.97CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy
title Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy
spellingShingle Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy
Gamarra Luques, Carlos Diego
Mifepristone
cancer de ovario
apoptosis
ciclo celular
title_short Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy
title_full Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy
title_fullStr Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy
title_full_unstemmed Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy
title_sort Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy
dc.creator.none.fl_str_mv Gamarra Luques, Carlos Diego
Goyeneche, Alicia A.
Hapon, María Belén
Telleria, Carlos Marcelo
author Gamarra Luques, Carlos Diego
author_facet Gamarra Luques, Carlos Diego
Goyeneche, Alicia A.
Hapon, María Belén
Telleria, Carlos Marcelo
author_role author
author2 Goyeneche, Alicia A.
Hapon, María Belén
Telleria, Carlos Marcelo
author2_role author
author
author
dc.subject.none.fl_str_mv Mifepristone
cancer de ovario
apoptosis
ciclo celular
topic Mifepristone
cancer de ovario
apoptosis
ciclo celular
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Advanced ovarian cancer is treated with cytoreductive surgery and combination platinum- and taxane-based chemotherapy. Although most patients have acute clinical response to this strategy, the disease ultimately recurs. In this work we questioned whether the synthetic steroid mifepristone, which as monotherapy inhibits the growth of ovarian cancer cells, is capable of preventing repopulation of ovarian cancer cells if given after a round of lethal cisplatin-paclitaxel combination treatment.Methods: We established an in vitro approach wherein ovarian cancer cells with various sensitivities to cisplatin or paclitaxel were exposed to a round of lethal doses of cisplatin for 1 h plus paclitaxel for 3 h. Thereafter, cells were maintained in media with or without mifepristone, and short- and long-term cytotoxicity was assessed.Results: Four days after treatment the lethality of cisplatin-paclitaxel was evidenced by reduced number of cells, increased hypodiploid DNA content, morphological features of apoptosis, DNA fragmentation, and cleavage of caspase-3, and of its downstream substrate PARP. Short-term presence of mifepristone either enhanced or did not modify such acute lethality. Seven days after receiving cisplatin-paclitaxel, cultures showed signs of relapse with escaping colonies that repopulated the plate in a time-dependent manner. Conversely, cultures exposed to cisplatin-paclitaxel followed by mifepristone not only did not display signs of repopulation following initial chemotherapy, but they also had their clonogenic capacity drastically reduced when compared to cells repopulating after cisplatin-paclitaxel.Conclusions: Cytostatic concentrations of mifepristone after exposure to lethal doses of cisplatin and paclitaxel in combination blocks repopulation of remnant cells surviving and escaping the cytotoxic drugs.
Fil: Gamarra Luques, Carlos Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University Of South Dakota. Sanford School Of Medicine; Estados Unidos
Fil: Goyeneche, Alicia A.. University Of South Dakota. Sanford School Of Medicine; Estados Unidos
Fil: Hapon, María Belén. University Of South Dakota. Sanford School Of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Telleria, Carlos Marcelo. University Of South Dakota. Sanford School Of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Background: Advanced ovarian cancer is treated with cytoreductive surgery and combination platinum- and taxane-based chemotherapy. Although most patients have acute clinical response to this strategy, the disease ultimately recurs. In this work we questioned whether the synthetic steroid mifepristone, which as monotherapy inhibits the growth of ovarian cancer cells, is capable of preventing repopulation of ovarian cancer cells if given after a round of lethal cisplatin-paclitaxel combination treatment.Methods: We established an in vitro approach wherein ovarian cancer cells with various sensitivities to cisplatin or paclitaxel were exposed to a round of lethal doses of cisplatin for 1 h plus paclitaxel for 3 h. Thereafter, cells were maintained in media with or without mifepristone, and short- and long-term cytotoxicity was assessed.Results: Four days after treatment the lethality of cisplatin-paclitaxel was evidenced by reduced number of cells, increased hypodiploid DNA content, morphological features of apoptosis, DNA fragmentation, and cleavage of caspase-3, and of its downstream substrate PARP. Short-term presence of mifepristone either enhanced or did not modify such acute lethality. Seven days after receiving cisplatin-paclitaxel, cultures showed signs of relapse with escaping colonies that repopulated the plate in a time-dependent manner. Conversely, cultures exposed to cisplatin-paclitaxel followed by mifepristone not only did not display signs of repopulation following initial chemotherapy, but they also had their clonogenic capacity drastically reduced when compared to cells repopulating after cisplatin-paclitaxel.Conclusions: Cytostatic concentrations of mifepristone after exposure to lethal doses of cisplatin and paclitaxel in combination blocks repopulation of remnant cells surviving and escaping the cytotoxic drugs.
publishDate 2012
dc.date.none.fl_str_mv 2012-05
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/11336/81171
Gamarra Luques, Carlos Diego; Goyeneche, Alicia A.; Hapon, María Belén; Telleria, Carlos Marcelo; Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy; BioMed Central; BMC Cancer; 12; 5-2012; 1-16
1471-2407
CONICET Digital
CONICET
url http://hdl.handle.net/11336/81171
identifier_str_mv Gamarra Luques, Carlos Diego; Goyeneche, Alicia A.; Hapon, María Belén; Telleria, Carlos Marcelo; Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy; BioMed Central; BMC Cancer; 12; 5-2012; 1-16
1471-2407
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-200
info:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2407-12-200
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 BioMed Central
publisher.none.fl_str_mv BioMed Central
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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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