Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn

Autores
Silva, I. T.; Teixeira, Marina R.; Lang, Karen L.; Guimarães, Tatiana da R.; Dudek, Sabine E.; Duran, Fernando Javier; Ludwig, Stephan; Caro, Miguel S. B.; Schenkel, Eloir P.; Simoes, Cláudia M. O.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cancer represents a major public health problem from all over the world and the lung carcinoma is the leading cause of cancer death. In this sense, the aim of the present study was to examine the cytotoxic effects of a novel Cucurbitacin (Cuc1) isolated from Wilbrandia ebracteata on human non-small-cell lung cancer (A549). In order to achieve this aim, the cell proliferation was measured by MTT assay and actin cytoskeleton was stained by rhodamine-phalloidin, whereas, the cell cycle distribution and apoptosis induction were quantified using flow cytometry. The signal transduction profiling of Cuc1 treated cells, as well as the levels of apoptotic proteins were analyzed by Western blotting. Cuc1 significantly inhibited cell growth showing IC50 values of 13.5±1.8 and 3.8±0.4 μM for 48 and 72 h of treatment, respectively. Additionally, Cuc1 arrested cell cycle at G2/M phase, disrupted the actin dynamics and induced apoptosis since the amount of apoptotic cells increased from 5.18±0.585% in the untreated cells to 73.82±0.545% in the treated cells. Detailed analysis on the mechanism of action revealed that Cuc1 inhibited the phosphorylation of Protein Kinase B (PKB/AKT) and Signal Transducer and Activator of Transcription (STAT3) signaling pathways, down-regulating the expression of Bcl-2 and consequently inducing cytochrome c release from the mitochondria to the cytosol. These results suggest that the Cuc1 could be a potential candidate for cancer chemotherapy agent.
Fil: Silva, I. T.. Universidade Federal de Santa Catarina; Brasil
Fil: Teixeira, Marina R.. Universidade Federal de Santa Catarina; Brasil
Fil: Lang, Karen L.. Universidade Federal de Santa Catarina; Brasil
Fil: Guimarães, Tatiana da R.. Universidade Federal de Santa Catarina; Brasil
Fil: Dudek, Sabine E.. University of Münster; 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: Ludwig, Stephan. University of Münster; Alemania
Fil: Caro, Miguel S. B.. Universidade Federal de Santa Catarina; Brasil
Fil: Schenkel, Eloir P.. Universidade Federal de Santa Catarina; Brasil
Fil: Simoes, Cláudia M. O.. Universidade Federal de Santa Catarina; Brasil
Materia
CUCURBITACINS
LUNG CANCER
A549 CELL
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:11336/26914
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/26914
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata CognSilva, I. T.Teixeira, Marina R.Lang, Karen L.Guimarães, Tatiana da R.Dudek, Sabine E.Duran, Fernando JavierLudwig, StephanCaro, Miguel S. B.Schenkel, Eloir P.Simoes, Cláudia M. O.CUCURBITACINSLUNG CANCERA549 CELLhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cancer represents a major public health problem from all over the world and the lung carcinoma is the leading cause of cancer death. In this sense, the aim of the present study was to examine the cytotoxic effects of a novel Cucurbitacin (Cuc1) isolated from Wilbrandia ebracteata on human non-small-cell lung cancer (A549). In order to achieve this aim, the cell proliferation was measured by MTT assay and actin cytoskeleton was stained by rhodamine-phalloidin, whereas, the cell cycle distribution and apoptosis induction were quantified using flow cytometry. The signal transduction profiling of Cuc1 treated cells, as well as the levels of apoptotic proteins were analyzed by Western blotting. Cuc1 significantly inhibited cell growth showing IC50 values of 13.5±1.8 and 3.8±0.4 μM for 48 and 72 h of treatment, respectively. Additionally, Cuc1 arrested cell cycle at G2/M phase, disrupted the actin dynamics and induced apoptosis since the amount of apoptotic cells increased from 5.18±0.585% in the untreated cells to 73.82±0.545% in the treated cells. Detailed analysis on the mechanism of action revealed that Cuc1 inhibited the phosphorylation of Protein Kinase B (PKB/AKT) and Signal Transducer and Activator of Transcription (STAT3) signaling pathways, down-regulating the expression of Bcl-2 and consequently inducing cytochrome c release from the mitochondria to the cytosol. These results suggest that the Cuc1 could be a potential candidate for cancer chemotherapy agent.Fil: Silva, I. T.. Universidade Federal de Santa Catarina; BrasilFil: Teixeira, Marina R.. Universidade Federal de Santa Catarina; BrasilFil: Lang, Karen L.. Universidade Federal de Santa Catarina; BrasilFil: Guimarães, Tatiana da R.. Universidade Federal de Santa Catarina; BrasilFil: Dudek, Sabine E.. University of Münster; 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: Ludwig, Stephan. University of Münster; AlemaniaFil: Caro, Miguel S. B.. Universidade Federal de Santa Catarina; BrasilFil: Schenkel, Eloir P.. Universidade Federal de Santa Catarina; BrasilFil: Simoes, Cláudia M. O.. Universidade Federal de Santa Catarina; BrasilScience Alert2013-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/26914Silva, I. T.; Teixeira, Marina R.; Lang, Karen L.; Guimarães, Tatiana da R.; Dudek, Sabine E.; et al.; Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn; Science Alert; International Journal of Cancer Research; 9; 2; 5-2013; 54-681811-97271811-9735CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3923/ijcr.2013.54.68info:eu-repo/semantics/altIdentifier/url/http://www.scialert.net/abstract/?doi=ijcr.2013.54.68info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:23:33Zoai:ri.conicet.gov.ar:11336/26914instacron: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 14:23:34.21CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn
title Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn
spellingShingle Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn
Silva, I. T.
CUCURBITACINS
LUNG CANCER
A549 CELL
title_short Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn
title_full Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn
title_fullStr Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn
title_full_unstemmed Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn
title_sort Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn
dc.creator.none.fl_str_mv Silva, I. T.
Teixeira, Marina R.
Lang, Karen L.
Guimarães, Tatiana da R.
Dudek, Sabine E.
Duran, Fernando Javier
Ludwig, Stephan
Caro, Miguel S. B.
Schenkel, Eloir P.
Simoes, Cláudia M. O.
author Silva, I. T.
author_facet Silva, I. T.
Teixeira, Marina R.
Lang, Karen L.
Guimarães, Tatiana da R.
Dudek, Sabine E.
Duran, Fernando Javier
Ludwig, Stephan
Caro, Miguel S. B.
Schenkel, Eloir P.
Simoes, Cláudia M. O.
author_role author
author2 Teixeira, Marina R.
Lang, Karen L.
Guimarães, Tatiana da R.
Dudek, Sabine E.
Duran, Fernando Javier
Ludwig, Stephan
Caro, Miguel S. B.
Schenkel, Eloir P.
Simoes, Cláudia M. O.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CUCURBITACINS
LUNG CANCER
A549 CELL
topic CUCURBITACINS
LUNG CANCER
A549 CELL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cancer represents a major public health problem from all over the world and the lung carcinoma is the leading cause of cancer death. In this sense, the aim of the present study was to examine the cytotoxic effects of a novel Cucurbitacin (Cuc1) isolated from Wilbrandia ebracteata on human non-small-cell lung cancer (A549). In order to achieve this aim, the cell proliferation was measured by MTT assay and actin cytoskeleton was stained by rhodamine-phalloidin, whereas, the cell cycle distribution and apoptosis induction were quantified using flow cytometry. The signal transduction profiling of Cuc1 treated cells, as well as the levels of apoptotic proteins were analyzed by Western blotting. Cuc1 significantly inhibited cell growth showing IC50 values of 13.5±1.8 and 3.8±0.4 μM for 48 and 72 h of treatment, respectively. Additionally, Cuc1 arrested cell cycle at G2/M phase, disrupted the actin dynamics and induced apoptosis since the amount of apoptotic cells increased from 5.18±0.585% in the untreated cells to 73.82±0.545% in the treated cells. Detailed analysis on the mechanism of action revealed that Cuc1 inhibited the phosphorylation of Protein Kinase B (PKB/AKT) and Signal Transducer and Activator of Transcription (STAT3) signaling pathways, down-regulating the expression of Bcl-2 and consequently inducing cytochrome c release from the mitochondria to the cytosol. These results suggest that the Cuc1 could be a potential candidate for cancer chemotherapy agent.
Fil: Silva, I. T.. Universidade Federal de Santa Catarina; Brasil
Fil: Teixeira, Marina R.. Universidade Federal de Santa Catarina; Brasil
Fil: Lang, Karen L.. Universidade Federal de Santa Catarina; Brasil
Fil: Guimarães, Tatiana da R.. Universidade Federal de Santa Catarina; Brasil
Fil: Dudek, Sabine E.. University of Münster; 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: Ludwig, Stephan. University of Münster; Alemania
Fil: Caro, Miguel S. B.. Universidade Federal de Santa Catarina; Brasil
Fil: Schenkel, Eloir P.. Universidade Federal de Santa Catarina; Brasil
Fil: Simoes, Cláudia M. O.. Universidade Federal de Santa Catarina; Brasil
description Cancer represents a major public health problem from all over the world and the lung carcinoma is the leading cause of cancer death. In this sense, the aim of the present study was to examine the cytotoxic effects of a novel Cucurbitacin (Cuc1) isolated from Wilbrandia ebracteata on human non-small-cell lung cancer (A549). In order to achieve this aim, the cell proliferation was measured by MTT assay and actin cytoskeleton was stained by rhodamine-phalloidin, whereas, the cell cycle distribution and apoptosis induction were quantified using flow cytometry. The signal transduction profiling of Cuc1 treated cells, as well as the levels of apoptotic proteins were analyzed by Western blotting. Cuc1 significantly inhibited cell growth showing IC50 values of 13.5±1.8 and 3.8±0.4 μM for 48 and 72 h of treatment, respectively. Additionally, Cuc1 arrested cell cycle at G2/M phase, disrupted the actin dynamics and induced apoptosis since the amount of apoptotic cells increased from 5.18±0.585% in the untreated cells to 73.82±0.545% in the treated cells. Detailed analysis on the mechanism of action revealed that Cuc1 inhibited the phosphorylation of Protein Kinase B (PKB/AKT) and Signal Transducer and Activator of Transcription (STAT3) signaling pathways, down-regulating the expression of Bcl-2 and consequently inducing cytochrome c release from the mitochondria to the cytosol. These results suggest that the Cuc1 could be a potential candidate for cancer chemotherapy agent.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
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/11336/26914
Silva, I. T.; Teixeira, Marina R.; Lang, Karen L.; Guimarães, Tatiana da R.; Dudek, Sabine E.; et al.; Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn; Science Alert; International Journal of Cancer Research; 9; 2; 5-2013; 54-68
1811-9727
1811-9735
CONICET Digital
CONICET
url http://hdl.handle.net/11336/26914
identifier_str_mv Silva, I. T.; Teixeira, Marina R.; Lang, Karen L.; Guimarães, Tatiana da R.; Dudek, Sabine E.; et al.; Proliferative Inhibition and Apoptotic Mechanism on Human Non-small-cell Lung Cancer (A549 Cells) of a Novel Cucurbitacin from Wilbrandia ebracteata Cogn; Science Alert; International Journal of Cancer Research; 9; 2; 5-2013; 54-68
1811-9727
1811-9735
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3923/ijcr.2013.54.68
info:eu-repo/semantics/altIdentifier/url/http://www.scialert.net/abstract/?doi=ijcr.2013.54.68
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 Science Alert
publisher.none.fl_str_mv Science Alert
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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