Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Fogaça, Manoela Viar, Cândido-Bacani, Priscila de Matos, Benicio, Lucas Milanez, Zapata, Lara Martinelli, Cardoso, Priscilla de Freitas, de Oliveira, Marcelo Tempesta, Calvo, Tamara Regina, Varanda, Eliana Aparecida, Vilegas, Wagner, de Syllos Cólus, Ilce Mara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011876/
https://www.ncbi.nlm.nih.gov/pubmed/28738722
http://dx.doi.org/10.1080/13880209.2017.1354387
_version_ 1783496144653910016
author Fogaça, Manoela Viar
Cândido-Bacani, Priscila de Matos
Benicio, Lucas Milanez
Zapata, Lara Martinelli
Cardoso, Priscilla de Freitas
de Oliveira, Marcelo Tempesta
Calvo, Tamara Regina
Varanda, Eliana Aparecida
Vilegas, Wagner
de Syllos Cólus, Ilce Mara
author_facet Fogaça, Manoela Viar
Cândido-Bacani, Priscila de Matos
Benicio, Lucas Milanez
Zapata, Lara Martinelli
Cardoso, Priscilla de Freitas
de Oliveira, Marcelo Tempesta
Calvo, Tamara Regina
Varanda, Eliana Aparecida
Vilegas, Wagner
de Syllos Cólus, Ilce Mara
author_sort Fogaça, Manoela Viar
collection PubMed
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 μM) or ISA (0.5 to 50 μM). 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 LD(50) – 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 μM) and HeLa cells (10 to 200 μM), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 μM; HeLa: 5 and 10 μM). 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.
format Online
Article
Text
id pubmed-7011876
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-70118762020-02-24 Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression Fogaça, Manoela Viar Cândido-Bacani, Priscila de Matos Benicio, Lucas Milanez Zapata, Lara Martinelli Cardoso, Priscilla de Freitas de Oliveira, Marcelo Tempesta Calvo, Tamara Regina Varanda, Eliana Aparecida Vilegas, Wagner de Syllos Cólus, Ilce Mara Pharm Biol Research Article 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 μM) or ISA (0.5 to 50 μM). 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 LD(50) – 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 μM) and HeLa cells (10 to 200 μM), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 μM; HeLa: 5 and 10 μM). 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. Taylor & Francis 2017-07-25 /pmc/articles/PMC7011876/ /pubmed/28738722 http://dx.doi.org/10.1080/13880209.2017.1354387 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Fogaça, Manoela Viar
Cândido-Bacani, Priscila de Matos
Benicio, Lucas Milanez
Zapata, Lara Martinelli
Cardoso, Priscilla de Freitas
de Oliveira, Marcelo Tempesta
Calvo, Tamara Regina
Varanda, Eliana Aparecida
Vilegas, Wagner
de Syllos Cólus, Ilce Mara
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
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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011876/
https://www.ncbi.nlm.nih.gov/pubmed/28738722
http://dx.doi.org/10.1080/13880209.2017.1354387
work_keys_str_mv AT fogacamanoelaviar effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression
AT candidobacaniprisciladematos effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression
AT beniciolucasmilanez effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression
AT zapatalaramartinelli effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression
AT cardosopriscilladefreitas effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression
AT deoliveiramarcelotempesta effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression
AT calvotamararegina effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression
AT varandaelianaaparecida effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression
AT vilegaswagner effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression
AT desylloscolusilcemara effectsofindirubinandisatinoncellviabilitymutagenicitygenotoxicityandbaxercc1geneexpression