In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B

Autores
Silva, Izabella T.; Carvalho, Annelise; Lang, Karen L.; Dudek, Sabine E.; Masemann, Dörthe; Duran, Fernando Javier; Caro, Miguel S. B.; Rapp, Ulf R.; Wixler, Viktor; Schenkel, Eloir P.; Simoes, Cláudia M. O.; Ludwig, Stephan
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug.
Fil: Silva, Izabella T.. Universidade Federal Da Santa Catarina; Brasil. Westfalische Wilhelms Universitat; Alemania
Fil: Carvalho, Annelise. Universidade Federal Da Santa Catarina; Brasil
Fil: Lang, Karen L.. Universidade Federal Da Santa Catarina; Brasil
Fil: Dudek, Sabine E.. Westfalische Wilhelms Universitat; Alemania
Fil: Masemann, Dörthe. Westfalische Wilhelms Universitat; Alemania
Fil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina
Fil: Caro, Miguel S. B.. Universidade Federal Da Santa Catarina; Brasil
Fil: Rapp, Ulf R.. Max Planck Institute for Heart and Lung Research; Alemania
Fil: Wixler, Viktor.
Fil: Schenkel, Eloir P.. Universidade Federal Da Santa Catarina; Brasil
Fil: Simoes, Cláudia M. O.. Universidade Federal Da Santa Catarina; Brasil
Fil: Ludwig, Stephan. Westfalische Wilhelms Universitat; Alemania
Materia
CUCURBITACINA
CÁNCER PULMON
DACE
APOPTOSIS
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:11336/18713
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/18713
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin BSilva, Izabella T.Carvalho, AnneliseLang, Karen L.Dudek, Sabine E.Masemann, DörtheDuran, Fernando JavierCaro, Miguel S. B.Rapp, Ulf R.Wixler, ViktorSchenkel, Eloir P.Simoes, Cláudia M. O.Ludwig, StephanCUCURBITACINACÁNCER PULMONDACEAPOPTOSIShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug.Fil: Silva, Izabella T.. Universidade Federal Da Santa Catarina; Brasil. Westfalische Wilhelms Universitat; AlemaniaFil: Carvalho, Annelise. Universidade Federal Da Santa Catarina; BrasilFil: Lang, Karen L.. Universidade Federal Da Santa Catarina; BrasilFil: Dudek, Sabine E.. Westfalische Wilhelms Universitat; AlemaniaFil: Masemann, Dörthe. Westfalische Wilhelms Universitat; AlemaniaFil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Caro, Miguel S. B.. Universidade Federal Da Santa Catarina; BrasilFil: Rapp, Ulf R.. Max Planck Institute for Heart and Lung Research; AlemaniaFil: Wixler, Viktor.Fil: Schenkel, Eloir P.. Universidade Federal Da Santa Catarina; BrasilFil: Simoes, Cláudia M. O.. Universidade Federal Da Santa Catarina; BrasilFil: Ludwig, Stephan. Westfalische Wilhelms Universitat; AlemaniaPublic Library of Science2015-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18713Silva, Izabella T.; Carvalho, Annelise; Lang, Karen L.; Dudek, Sabine E.; Masemann, Dörthe; et al.; In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B; Public Library of Science; Plos One; 10; 2; 2-2015; 1-19; e01177941932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0117794info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117794info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:42:56Zoai:ri.conicet.gov.ar:11336/18713instacron: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:34982025-09-29 09:42:56.35CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B
title In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B
spellingShingle In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B
Silva, Izabella T.
CUCURBITACINA
CÁNCER PULMON
DACE
APOPTOSIS
title_short In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B
title_full In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B
title_fullStr In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B
title_full_unstemmed In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B
title_sort In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B
dc.creator.none.fl_str_mv Silva, Izabella T.
Carvalho, Annelise
Lang, Karen L.
Dudek, Sabine E.
Masemann, Dörthe
Duran, Fernando Javier
Caro, Miguel S. B.
Rapp, Ulf R.
Wixler, Viktor
Schenkel, Eloir P.
Simoes, Cláudia M. O.
Ludwig, Stephan
author Silva, Izabella T.
author_facet Silva, Izabella T.
Carvalho, Annelise
Lang, Karen L.
Dudek, Sabine E.
Masemann, Dörthe
Duran, Fernando Javier
Caro, Miguel S. B.
Rapp, Ulf R.
Wixler, Viktor
Schenkel, Eloir P.
Simoes, Cláudia M. O.
Ludwig, Stephan
author_role author
author2 Carvalho, Annelise
Lang, Karen L.
Dudek, Sabine E.
Masemann, Dörthe
Duran, Fernando Javier
Caro, Miguel S. B.
Rapp, Ulf R.
Wixler, Viktor
Schenkel, Eloir P.
Simoes, Cláudia M. O.
Ludwig, Stephan
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CUCURBITACINA
CÁNCER PULMON
DACE
APOPTOSIS
topic CUCURBITACINA
CÁNCER PULMON
DACE
APOPTOSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug.
Fil: Silva, Izabella T.. Universidade Federal Da Santa Catarina; Brasil. Westfalische Wilhelms Universitat; Alemania
Fil: Carvalho, Annelise. Universidade Federal Da Santa Catarina; Brasil
Fil: Lang, Karen L.. Universidade Federal Da Santa Catarina; Brasil
Fil: Dudek, Sabine E.. Westfalische Wilhelms Universitat; Alemania
Fil: Masemann, Dörthe. Westfalische Wilhelms Universitat; Alemania
Fil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina
Fil: Caro, Miguel S. B.. Universidade Federal Da Santa Catarina; Brasil
Fil: Rapp, Ulf R.. Max Planck Institute for Heart and Lung Research; Alemania
Fil: Wixler, Viktor.
Fil: Schenkel, Eloir P.. Universidade Federal Da Santa Catarina; Brasil
Fil: Simoes, Cláudia M. O.. Universidade Federal Da Santa Catarina; Brasil
Fil: Ludwig, Stephan. Westfalische Wilhelms Universitat; Alemania
description Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug.
publishDate 2015
dc.date.none.fl_str_mv 2015-02
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/11336/18713
Silva, Izabella T.; Carvalho, Annelise; Lang, Karen L.; Dudek, Sabine E.; Masemann, Dörthe; et al.; In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B; Public Library of Science; Plos One; 10; 2; 2-2015; 1-19; e0117794
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18713
identifier_str_mv Silva, Izabella T.; Carvalho, Annelise; Lang, Karen L.; Dudek, Sabine E.; Masemann, Dörthe; et al.; In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B; Public Library of Science; Plos One; 10; 2; 2-2015; 1-19; e0117794
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0117794
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117794
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 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 13.069144

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