Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression

Detalhes bibliográficos
Autor(a) principal: Fogaca, Manoela Viar
Data de Publicação: 2017
Outros Autores: Candido-Bacani, Priscila de Matos, Benicio, Lucas Milanez, Zapata, Lara Martinelli, Cardoso, Priscilla de Freitas, Oliveira, Marcelo Tempesta de, Calvo, Tamara Regina [UNESP], Varanda, Eliana Aparecida [UNESP], Vilegas, Wagner [UNESP], Syllos Colus, Ilce Mara de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1080/13880209.2017.1354387
http://hdl.handle.net/11449/163048
Resumo: Context: Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood. Objective: We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN-and ISA-induced expression of ERCC1 or BAX genes. Materials and methods: HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN (0.1 to 200 mu M) or ISA (0.5 to 50 mu M). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100 and 150 mg/kg determined from the LD50 - 1 g/kg b.w.) and submitted to comet assay in vivo. Results: IRN reduced the viability of CHO-K1 (24 h; 5 to 200 mu M) and HeLa cells (10 to 200 mu M), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 mu M; HeLa: 5 and 10 mu M). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced genotoxicity in vivo (4 h). Conclusion: IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations.
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spelling Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expressionIndigofera suffruticosaIndigofera truxillensisHeLa cellsCHO-K1 cellscytokinesis-blocked micronucleus assaycomet assayapoptosisContext: Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood. Objective: We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN-and ISA-induced expression of ERCC1 or BAX genes. Materials and methods: HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN (0.1 to 200 mu M) or ISA (0.5 to 50 mu M). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100 and 150 mg/kg determined from the LD50 - 1 g/kg b.w.) and submitted to comet assay in vivo. Results: IRN reduced the viability of CHO-K1 (24 h; 5 to 200 mu M) and HeLa cells (10 to 200 mu M), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 mu M; HeLa: 5 and 10 mu M). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced genotoxicity in vivo (4 h). Conclusion: IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Estadual Londrina, Ctr Biol Sci, Dept Gen Biol, Celso Garcia Cid Rd,PR 445 Km 380, BR-86057970 Londrina, Parana, BrazilSao Paulo State Univ, Araraquara Inst Chem, Araraquara, BrazilSao Paulo State Univ, Araraquara Fac Pharmaceut Sci, Dept Biol Sci, Araraquara, BrazilSao Paulo State Univ, Expt Campus Paulista Coast, Sao Vicente, BrazilYale Sch Med, Abraham Ribicoff Res Facil, New Haven, CT USASao Paulo State Univ, Araraquara Inst Chem, Araraquara, BrazilSao Paulo State Univ, Araraquara Fac Pharmaceut Sci, Dept Biol Sci, Araraquara, BrazilSao Paulo State Univ, Expt Campus Paulista Coast, Sao Vicente, BrazilTaylor & Francis LtdUniversidade Estadual de Londrina (UEL)Universidade Estadual Paulista (Unesp)Yale Sch MedFogaca, Manoela ViarCandido-Bacani, Priscila de MatosBenicio, Lucas MilanezZapata, Lara MartinelliCardoso, Priscilla de FreitasOliveira, Marcelo Tempesta deCalvo, Tamara Regina [UNESP]Varanda, Eliana Aparecida [UNESP]Vilegas, Wagner [UNESP]Syllos Colus, Ilce Mara de2018-11-26T17:39:53Z2018-11-26T17:39:53Z2017-07-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2005-2014application/pdfhttp://dx.doi.org/10.1080/13880209.2017.1354387Pharmaceutical Biology. Abingdon: Taylor & Francis Ltd, v. 55, n. 1, p. 2005-2014, 2017.1388-0209http://hdl.handle.net/11449/16304810.1080/13880209.2017.1354387WOS:000406287500001WOS000406287500001.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPharmaceutical Biology0,563info:eu-repo/semantics/openAccess2024-06-24T13:07:13Zoai:repositorio.unesp.br:11449/163048Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T15:10:43.512867Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression
title Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression
spellingShingle Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression
Fogaca, Manoela Viar
Indigofera suffruticosa
Indigofera truxillensis
HeLa cells
CHO-K1 cells
cytokinesis-blocked micronucleus assay
comet assay
apoptosis
title_short Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression
title_full Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression
title_fullStr Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression
title_full_unstemmed Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression
title_sort Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression
author Fogaca, Manoela Viar
author_facet Fogaca, Manoela Viar
Candido-Bacani, Priscila de Matos
Benicio, Lucas Milanez
Zapata, Lara Martinelli
Cardoso, Priscilla de Freitas
Oliveira, Marcelo Tempesta de
Calvo, Tamara Regina [UNESP]
Varanda, Eliana Aparecida [UNESP]
Vilegas, Wagner [UNESP]
Syllos Colus, Ilce Mara de
author_role author
author2 Candido-Bacani, Priscila de Matos
Benicio, Lucas Milanez
Zapata, Lara Martinelli
Cardoso, Priscilla de Freitas
Oliveira, Marcelo Tempesta de
Calvo, Tamara Regina [UNESP]
Varanda, Eliana Aparecida [UNESP]
Vilegas, Wagner [UNESP]
Syllos Colus, Ilce Mara de
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual de Londrina (UEL)
Universidade Estadual Paulista (Unesp)
Yale Sch Med
dc.contributor.author.fl_str_mv Fogaca, Manoela Viar
Candido-Bacani, Priscila de Matos
Benicio, Lucas Milanez
Zapata, Lara Martinelli
Cardoso, Priscilla de Freitas
Oliveira, Marcelo Tempesta de
Calvo, Tamara Regina [UNESP]
Varanda, Eliana Aparecida [UNESP]
Vilegas, Wagner [UNESP]
Syllos Colus, Ilce Mara de
dc.subject.por.fl_str_mv Indigofera suffruticosa
Indigofera truxillensis
HeLa cells
CHO-K1 cells
cytokinesis-blocked micronucleus assay
comet assay
apoptosis
topic Indigofera suffruticosa
Indigofera truxillensis
HeLa cells
CHO-K1 cells
cytokinesis-blocked micronucleus assay
comet assay
apoptosis
description Context: Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood. Objective: We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN-and ISA-induced expression of ERCC1 or BAX genes. Materials and methods: HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN (0.1 to 200 mu M) or ISA (0.5 to 50 mu M). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100 and 150 mg/kg determined from the LD50 - 1 g/kg b.w.) and submitted to comet assay in vivo. Results: IRN reduced the viability of CHO-K1 (24 h; 5 to 200 mu M) and HeLa cells (10 to 200 mu M), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 mu M; HeLa: 5 and 10 mu M). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced genotoxicity in vivo (4 h). Conclusion: IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations.
publishDate 2017
dc.date.none.fl_str_mv 2017-07-25
2018-11-26T17:39:53Z
2018-11-26T17:39:53Z
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/10.1080/13880209.2017.1354387
Pharmaceutical Biology. Abingdon: Taylor & Francis Ltd, v. 55, n. 1, p. 2005-2014, 2017.
1388-0209
http://hdl.handle.net/11449/163048
10.1080/13880209.2017.1354387
WOS:000406287500001
WOS000406287500001.pdf
url http://dx.doi.org/10.1080/13880209.2017.1354387
http://hdl.handle.net/11449/163048
identifier_str_mv Pharmaceutical Biology. Abingdon: Taylor & Francis Ltd, v. 55, n. 1, p. 2005-2014, 2017.
1388-0209
10.1080/13880209.2017.1354387
WOS:000406287500001
WOS000406287500001.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Pharmaceutical Biology
0,563
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 2005-2014
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis Ltd
publisher.none.fl_str_mv Taylor & Francis Ltd
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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