Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status

Detalhes bibliográficos
Autor(a) principal: Oliveira, Daiane Teixeira de
Data de Publicação: 2017
Outros Autores: Ventura Savio, Andre Luiz [UNESP], Castro Marcondes, Joao Paulo de [UNESP], Barros, Tatiane Martins, Barbosa, Ludmila Correia, Favero Salvadori, Daisy Maria [UNESP], Silva, Glenda Nicioli da
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1007/s12038-016-9654-5
http://hdl.handle.net/11449/162556
Resumo: Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated. Silibinin promoted decreased proliferation and increased late apoptosis in TP53 mutated cells. Increased early apoptosis rates, primary DNA damage, and decrease of cell colonies in the clonogenic survival assay were detected in both RT4 and T24 cell lines. Down-regulation of FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 expression occurred in RT4 cells. Modulation of miR203 was observed in both cell lines. In conclusion, despite the reduction of clone formation in both cell lines, the toxicogenomic effect of silibinin on FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 was dependent on the TP53 status. Taken together, the data confirmed the role of silibinin as an antiproliferative compound, whose mechanism of action was related to the TP53 status.
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spelling Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 statusBladder cancercell proliferationgenotoxicityPI3K/AKT/FRAP-mTOR pathwaysilibininTP53 geneSilibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated. Silibinin promoted decreased proliferation and increased late apoptosis in TP53 mutated cells. Increased early apoptosis rates, primary DNA damage, and decrease of cell colonies in the clonogenic survival assay were detected in both RT4 and T24 cell lines. Down-regulation of FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 expression occurred in RT4 cells. Modulation of miR203 was observed in both cell lines. In conclusion, despite the reduction of clone formation in both cell lines, the toxicogenomic effect of silibinin on FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 was dependent on the TP53 status. Taken together, the data confirmed the role of silibinin as an antiproliferative compound, whose mechanism of action was related to the TP53 status.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de Ouro Preto (UFOP)Univ Fed Ouro Preto, Dept Anal Clin, Escola Farm, Ouro Preto, MG, BrazilUniv Estadual Paulista, Fac Med Botucatu, Dept Patol, Botucatu, SP, BrazilUniv Estadual Paulista, Dept Genet, Inst Biociencias Botucatu, Botucatu, SP, BrazilUniv Estadual Paulista, Fac Med Botucatu, Dept Patol, Botucatu, SP, BrazilUniv Estadual Paulista, Dept Genet, Inst Biociencias Botucatu, Botucatu, SP, BrazilFAPESP: FAPESP- 2008/09147-6FAPEMIG: CBB-APQ-01497-14CNPq: CNPq- 41836/2014-3Indian Acad SciencesUniv Fed Ouro PretoUniversidade Estadual Paulista (Unesp)Oliveira, Daiane Teixeira deVentura Savio, Andre Luiz [UNESP]Castro Marcondes, Joao Paulo de [UNESP]Barros, Tatiane MartinsBarbosa, Ludmila CorreiaFavero Salvadori, Daisy Maria [UNESP]Silva, Glenda Nicioli da2018-11-26T17:20:55Z2018-11-26T17:20:55Z2017-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article91-101application/pdfhttp://dx.doi.org/10.1007/s12038-016-9654-5Journal Of Biosciences. Bangalore: Indian Acad Sciences, v. 42, n. 1, p. 91-101, 2017.0250-5991http://hdl.handle.net/11449/16255610.1007/s12038-016-9654-5WOS:000396027800011WOS000396027800011.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal Of Biosciences0,651info:eu-repo/semantics/openAccess2024-09-03T13:18:23Zoai:repositorio.unesp.br:11449/162556Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:18:23Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status
title Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status
spellingShingle Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status
Oliveira, Daiane Teixeira de
Bladder cancer
cell proliferation
genotoxicity
PI3K/AKT/FRAP-mTOR pathway
silibinin
TP53 gene
title_short Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status
title_full Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status
title_fullStr Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status
title_full_unstemmed Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status
title_sort Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status
author Oliveira, Daiane Teixeira de
author_facet Oliveira, Daiane Teixeira de
Ventura Savio, Andre Luiz [UNESP]
Castro Marcondes, Joao Paulo de [UNESP]
Barros, Tatiane Martins
Barbosa, Ludmila Correia
Favero Salvadori, Daisy Maria [UNESP]
Silva, Glenda Nicioli da
author_role author
author2 Ventura Savio, Andre Luiz [UNESP]
Castro Marcondes, Joao Paulo de [UNESP]
Barros, Tatiane Martins
Barbosa, Ludmila Correia
Favero Salvadori, Daisy Maria [UNESP]
Silva, Glenda Nicioli da
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Univ Fed Ouro Preto
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Oliveira, Daiane Teixeira de
Ventura Savio, Andre Luiz [UNESP]
Castro Marcondes, Joao Paulo de [UNESP]
Barros, Tatiane Martins
Barbosa, Ludmila Correia
Favero Salvadori, Daisy Maria [UNESP]
Silva, Glenda Nicioli da
dc.subject.por.fl_str_mv Bladder cancer
cell proliferation
genotoxicity
PI3K/AKT/FRAP-mTOR pathway
silibinin
TP53 gene
topic Bladder cancer
cell proliferation
genotoxicity
PI3K/AKT/FRAP-mTOR pathway
silibinin
TP53 gene
description Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated. Silibinin promoted decreased proliferation and increased late apoptosis in TP53 mutated cells. Increased early apoptosis rates, primary DNA damage, and decrease of cell colonies in the clonogenic survival assay were detected in both RT4 and T24 cell lines. Down-regulation of FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 expression occurred in RT4 cells. Modulation of miR203 was observed in both cell lines. In conclusion, despite the reduction of clone formation in both cell lines, the toxicogenomic effect of silibinin on FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 was dependent on the TP53 status. Taken together, the data confirmed the role of silibinin as an antiproliferative compound, whose mechanism of action was related to the TP53 status.
publishDate 2017
dc.date.none.fl_str_mv 2017-03-01
2018-11-26T17:20:55Z
2018-11-26T17:20:55Z
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/10.1007/s12038-016-9654-5
Journal Of Biosciences. Bangalore: Indian Acad Sciences, v. 42, n. 1, p. 91-101, 2017.
0250-5991
http://hdl.handle.net/11449/162556
10.1007/s12038-016-9654-5
WOS:000396027800011
WOS000396027800011.pdf
url http://dx.doi.org/10.1007/s12038-016-9654-5
http://hdl.handle.net/11449/162556
identifier_str_mv Journal Of Biosciences. Bangalore: Indian Acad Sciences, v. 42, n. 1, p. 91-101, 2017.
0250-5991
10.1007/s12038-016-9654-5
WOS:000396027800011
WOS000396027800011.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal Of Biosciences
0,651
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 91-101
application/pdf
dc.publisher.none.fl_str_mv Indian Acad Sciences
publisher.none.fl_str_mv Indian Acad Sciences
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 repositoriounesp@unesp.br
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