Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , |
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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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 |
|
_version_ |
1808128475639316480 |