Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression

Detalhes bibliográficos
Autor(a) principal: Pereira, Rodrigo Machado
Data de Publicação: 2016
Outros Autores: Ferreira-Silva, Guilherme Alvaro, Pivatto, Marcos, Santos, Luciana de Avila [UNESP], Bolzani, Vanderlan da Silva [UNESP], Chagas de Paula, Daniela Aparecida, Oliveira, Jaqueline Carvalho de, Viegas Junior, Claudio, Ionta, Marisa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.tiv.2015.11.018
http://hdl.handle.net/11449/165064
Resumo: Cancer is one of the most critical problems of public health in the world and one of the main challenges for medicine in this century. Unfortunately, most patients are diagnosed at advanced stage, when the treatment options are palliative. Consequently, the search for novel therapeutic options is imperative. In the context, the plants represent an important source for discovering of novel compounds with pharmacological potential including antineoplastic agents. Herein, we aimed to investigate in vitro antiproliferative and cytotoxic potentials of an alkaloid mixture derived from Senna spectabilis, (-)-cassine (1) and (-)-spectaline (2). These alkaloids reduced cell viability in a concentration-dependent manner of six tumor cell lines. From initial screening, HepG2 cells were selected for further investigations. We show that alkaloids 1/2 have an important antiproliferative activity on HepG2 cells due to their ability in inducing cell cycle arrest in G1/S transition. This effect was associated to ERIC inactivation and down-regulation of cyclin D1 expression. In addition, we evidenced a disruption of the microfilaments and microtubules in a consequence of the treatment. Taken together, the data showed by the first time that alkaloids 1/2 strongly inhibit cell proliferation of hepatocellular carcinoma cells. Therefore, they represent promise antitumor compounds against liver cancer and should be considered for further anticancer in vivo studies. (C) 2015 Elsevier Ltd. All rights reserved.
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spelling Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expressionHepatocellular carcinomaCell cycle arrest(-)-Cassine(-)-SpectalinePiperidine alkaloidsSenna spectabilisCancer is one of the most critical problems of public health in the world and one of the main challenges for medicine in this century. Unfortunately, most patients are diagnosed at advanced stage, when the treatment options are palliative. Consequently, the search for novel therapeutic options is imperative. In the context, the plants represent an important source for discovering of novel compounds with pharmacological potential including antineoplastic agents. Herein, we aimed to investigate in vitro antiproliferative and cytotoxic potentials of an alkaloid mixture derived from Senna spectabilis, (-)-cassine (1) and (-)-spectaline (2). These alkaloids reduced cell viability in a concentration-dependent manner of six tumor cell lines. From initial screening, HepG2 cells were selected for further investigations. We show that alkaloids 1/2 have an important antiproliferative activity on HepG2 cells due to their ability in inducing cell cycle arrest in G1/S transition. This effect was associated to ERIC inactivation and down-regulation of cyclin D1 expression. In addition, we evidenced a disruption of the microfilaments and microtubules in a consequence of the treatment. Taken together, the data showed by the first time that alkaloids 1/2 strongly inhibit cell proliferation of hepatocellular carcinoma cells. Therefore, they represent promise antitumor compounds against liver cancer and should be considered for further anticancer in vivo studies. (C) 2015 Elsevier Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Brazilian Agency FINEPUniv Fed Alfenas, Inst Biomed Sci, BR-37130000 Alfenas, MG, BrazilUniv Fed Uberlandia, Inst Chem, Nucleus Res Nat Prod NuPPeN, BR-38408144 Uberlandia, MG, BrazilState Univ Sao Paulo, Inst Chem, BR-14801970 Araraquara, SP, BrazilUniv Fed Alfenas, Inst Chem, Lab Phytochem & Med Chem LFQM, BR-37130000 Alfenas, MG, BrazilUniv Fed Alfenas, Inst Nat Sci, BR-37130000 Alfenas, MG, BrazilUniv Fed Alfenas, Inst Chem, Lab Res Med Chem PeQuiM, BR-37130000 Alfenas, MG, BrazilState Univ Sao Paulo, Inst Chem, BR-14801970 Araraquara, SP, BrazilCNPq: 454088/2014-0CNPq: 573564/2008-6FAPEMIG: CEX-PPM-00241-15FAPEMIG: APQ-00341-13Elsevier B.V.Univ Fed AlfenasUniversidade Federal de Uberlândia (UFU)Universidade Estadual Paulista (Unesp)Pereira, Rodrigo MachadoFerreira-Silva, Guilherme AlvaroPivatto, MarcosSantos, Luciana de Avila [UNESP]Bolzani, Vanderlan da Silva [UNESP]Chagas de Paula, Daniela AparecidaOliveira, Jaqueline Carvalho deViegas Junior, ClaudioIonta, Marisa2018-11-27T08:57:07Z2018-11-27T08:57:07Z2016-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article86-92application/pdfhttp://dx.doi.org/10.1016/j.tiv.2015.11.018Toxicology In Vitro. Oxford: Pergamon-elsevier Science Ltd, v. 31, p. 86-92, 2016.0887-2333http://hdl.handle.net/11449/16506410.1016/j.tiv.2015.11.018WOS:000369879700010WOS000369879700010.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengToxicology In Vitro0,931info:eu-repo/semantics/openAccess2024-01-11T06:33:07Zoai:repositorio.unesp.br:11449/165064Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:43:52.895029Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression
title Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression
spellingShingle Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression
Pereira, Rodrigo Machado
Hepatocellular carcinoma
Cell cycle arrest
(-)-Cassine
(-)-Spectaline
Piperidine alkaloids
Senna spectabilis
title_short Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression
title_full Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression
title_fullStr Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression
title_full_unstemmed Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression
title_sort Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression
author Pereira, Rodrigo Machado
author_facet Pereira, Rodrigo Machado
Ferreira-Silva, Guilherme Alvaro
Pivatto, Marcos
Santos, Luciana de Avila [UNESP]
Bolzani, Vanderlan da Silva [UNESP]
Chagas de Paula, Daniela Aparecida
Oliveira, Jaqueline Carvalho de
Viegas Junior, Claudio
Ionta, Marisa
author_role author
author2 Ferreira-Silva, Guilherme Alvaro
Pivatto, Marcos
Santos, Luciana de Avila [UNESP]
Bolzani, Vanderlan da Silva [UNESP]
Chagas de Paula, Daniela Aparecida
Oliveira, Jaqueline Carvalho de
Viegas Junior, Claudio
Ionta, Marisa
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Univ Fed Alfenas
Universidade Federal de Uberlândia (UFU)
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Pereira, Rodrigo Machado
Ferreira-Silva, Guilherme Alvaro
Pivatto, Marcos
Santos, Luciana de Avila [UNESP]
Bolzani, Vanderlan da Silva [UNESP]
Chagas de Paula, Daniela Aparecida
Oliveira, Jaqueline Carvalho de
Viegas Junior, Claudio
Ionta, Marisa
dc.subject.por.fl_str_mv Hepatocellular carcinoma
Cell cycle arrest
(-)-Cassine
(-)-Spectaline
Piperidine alkaloids
Senna spectabilis
topic Hepatocellular carcinoma
Cell cycle arrest
(-)-Cassine
(-)-Spectaline
Piperidine alkaloids
Senna spectabilis
description Cancer is one of the most critical problems of public health in the world and one of the main challenges for medicine in this century. Unfortunately, most patients are diagnosed at advanced stage, when the treatment options are palliative. Consequently, the search for novel therapeutic options is imperative. In the context, the plants represent an important source for discovering of novel compounds with pharmacological potential including antineoplastic agents. Herein, we aimed to investigate in vitro antiproliferative and cytotoxic potentials of an alkaloid mixture derived from Senna spectabilis, (-)-cassine (1) and (-)-spectaline (2). These alkaloids reduced cell viability in a concentration-dependent manner of six tumor cell lines. From initial screening, HepG2 cells were selected for further investigations. We show that alkaloids 1/2 have an important antiproliferative activity on HepG2 cells due to their ability in inducing cell cycle arrest in G1/S transition. This effect was associated to ERIC inactivation and down-regulation of cyclin D1 expression. In addition, we evidenced a disruption of the microfilaments and microtubules in a consequence of the treatment. Taken together, the data showed by the first time that alkaloids 1/2 strongly inhibit cell proliferation of hepatocellular carcinoma cells. Therefore, they represent promise antitumor compounds against liver cancer and should be considered for further anticancer in vivo studies. (C) 2015 Elsevier Ltd. All rights reserved.
publishDate 2016
dc.date.none.fl_str_mv 2016-03-01
2018-11-27T08:57:07Z
2018-11-27T08:57:07Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.tiv.2015.11.018
Toxicology In Vitro. Oxford: Pergamon-elsevier Science Ltd, v. 31, p. 86-92, 2016.
0887-2333
http://hdl.handle.net/11449/165064
10.1016/j.tiv.2015.11.018
WOS:000369879700010
WOS000369879700010.pdf
url http://dx.doi.org/10.1016/j.tiv.2015.11.018
http://hdl.handle.net/11449/165064
identifier_str_mv Toxicology In Vitro. Oxford: Pergamon-elsevier Science Ltd, v. 31, p. 86-92, 2016.
0887-2333
10.1016/j.tiv.2015.11.018
WOS:000369879700010
WOS000369879700010.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxicology In Vitro
0,931
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 86-92
application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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