Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line

Detalhes bibliográficos
Autor(a) principal: De Quadros, Ana Paula Oliveira [UNESP]
Data de Publicação: 2023
Outros Autores: Oshiiwa, Bruna [UNESP], Petreanu, Marcel, Niero, Rivaldo, Rosa, Paulo Cesar Pires, Sawaya, Alexandra Christine Helena Frankland, Mantovani, Mario Sergio, O'Neill De Mascarenhas Gaivão, Isabel, Maistro, Edson Luis [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.tiv.2022.105485
http://hdl.handle.net/11449/249331
Resumo: Rubus rosifolius, popularly known as “red mulberry”, is a common medicinal plant in southern Brazil and is used as an antidiarrheal, analgesic, antimicrobial and antihypertensive, and to treat stomach diseases. The aim of this study was to analyze the R. rosifolius stem extract (RrSE) for possible in vitro cytotoxic and genotoxic effects, using the comet assay and the micronucleus test to assess genotoxicity, and flow cytometry to assess the impact on the cell cycle and apoptosis in HepG2/C3A cells, in addition to evaluating the expression of genes linked to the induction of DNA damage, cell cycle, apoptosis and metabolism of xenobiotics. The MTT assay observed no cytotoxic effects at concentrations between 0.01 and 100 μg/mL of the extract. However, genotoxic effects occurred in treatments with the extract from a 1 μg/mL concentration. Flow cytometry analysis revealed a significant increase in cells in the G2/M phase after treatment with 10 μg/mL, a decrease in cells in the G0/G1 phase in the treatment with 100 μg/mL, and a significant increase in total apoptotic cells. In the gene expression analysis, an increase in the CYP1A2 xenobiotics metabolizing gene expression was observed. Despite the promising pharmacological effects of R. rosifolius, the results revealed that the RrSE has genotoxic effect and induces apoptosis in HepG2/C3A cells, indicating danger in using this plant extract by humans.
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spelling Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell lineApoptosis analysisCell cycle analysisComet assayGene expressionMicronucleus testRubus rosifolius toxicityRubus rosifolius, popularly known as “red mulberry”, is a common medicinal plant in southern Brazil and is used as an antidiarrheal, analgesic, antimicrobial and antihypertensive, and to treat stomach diseases. The aim of this study was to analyze the R. rosifolius stem extract (RrSE) for possible in vitro cytotoxic and genotoxic effects, using the comet assay and the micronucleus test to assess genotoxicity, and flow cytometry to assess the impact on the cell cycle and apoptosis in HepG2/C3A cells, in addition to evaluating the expression of genes linked to the induction of DNA damage, cell cycle, apoptosis and metabolism of xenobiotics. The MTT assay observed no cytotoxic effects at concentrations between 0.01 and 100 μg/mL of the extract. However, genotoxic effects occurred in treatments with the extract from a 1 μg/mL concentration. Flow cytometry analysis revealed a significant increase in cells in the G2/M phase after treatment with 10 μg/mL, a decrease in cells in the G0/G1 phase in the treatment with 100 μg/mL, and a significant increase in total apoptotic cells. In the gene expression analysis, an increase in the CYP1A2 xenobiotics metabolizing gene expression was observed. Despite the promising pharmacological effects of R. rosifolius, the results revealed that the RrSE has genotoxic effect and induces apoptosis in HepG2/C3A cells, indicating danger in using this plant extract by humans.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)São Paulo State University UNESP Biosciences Institute Post-Graduate Program on General and Applied Biology, SPSão Paulo State University UNESP Faculty of Philosophy and Sciences Speech and Hearing Therapy Department, SPVale do Itajaí University (UNIVALI) Department of Biological Sciences, SCFaculty of Pharmaceutical Sciences University of Campinas, CampinasLondrina State University UEL Department of General Biology, PRUniversity of Trás-os-Montes and Alto Douro CECAV and Department of Genetics and BiotechnologySão Paulo State University UNESP Biosciences Institute Post-Graduate Program on General and Applied Biology, SPSão Paulo State University UNESP Faculty of Philosophy and Sciences Speech and Hearing Therapy Department, SPFAPESP: 2017/24149-4CNPq: 303604/2021-2Universidade Estadual Paulista (UNESP)Vale do Itajaí University (UNIVALI)Universidade Estadual de Campinas (UNICAMP)Universidade Estadual de Londrina (UEL)CECAV and Department of Genetics and BiotechnologyDe Quadros, Ana Paula Oliveira [UNESP]Oshiiwa, Bruna [UNESP]Petreanu, MarcelNiero, RivaldoRosa, Paulo Cesar PiresSawaya, Alexandra Christine Helena FranklandMantovani, Mario SergioO'Neill De Mascarenhas Gaivão, IsabelMaistro, Edson Luis [UNESP]2023-07-29T15:13:11Z2023-07-29T15:13:11Z2023-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.tiv.2022.105485Toxicology in Vitro, v. 86.1879-31770887-2333http://hdl.handle.net/11449/24933110.1016/j.tiv.2022.1054852-s2.0-85141279142Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengToxicology in Vitroinfo:eu-repo/semantics/openAccess2024-08-09T17:39:46Zoai:repositorio.unesp.br:11449/249331Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-09T17:39:46Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line
title Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line
spellingShingle Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line
De Quadros, Ana Paula Oliveira [UNESP]
Apoptosis analysis
Cell cycle analysis
Comet assay
Gene expression
Micronucleus test
Rubus rosifolius toxicity
title_short Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line
title_full Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line
title_fullStr Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line
title_full_unstemmed Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line
title_sort Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line
author De Quadros, Ana Paula Oliveira [UNESP]
author_facet De Quadros, Ana Paula Oliveira [UNESP]
Oshiiwa, Bruna [UNESP]
Petreanu, Marcel
Niero, Rivaldo
Rosa, Paulo Cesar Pires
Sawaya, Alexandra Christine Helena Frankland
Mantovani, Mario Sergio
O'Neill De Mascarenhas Gaivão, Isabel
Maistro, Edson Luis [UNESP]
author_role author
author2 Oshiiwa, Bruna [UNESP]
Petreanu, Marcel
Niero, Rivaldo
Rosa, Paulo Cesar Pires
Sawaya, Alexandra Christine Helena Frankland
Mantovani, Mario Sergio
O'Neill De Mascarenhas Gaivão, Isabel
Maistro, Edson Luis [UNESP]
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Vale do Itajaí University (UNIVALI)
Universidade Estadual de Campinas (UNICAMP)
Universidade Estadual de Londrina (UEL)
CECAV and Department of Genetics and Biotechnology
dc.contributor.author.fl_str_mv De Quadros, Ana Paula Oliveira [UNESP]
Oshiiwa, Bruna [UNESP]
Petreanu, Marcel
Niero, Rivaldo
Rosa, Paulo Cesar Pires
Sawaya, Alexandra Christine Helena Frankland
Mantovani, Mario Sergio
O'Neill De Mascarenhas Gaivão, Isabel
Maistro, Edson Luis [UNESP]
dc.subject.por.fl_str_mv Apoptosis analysis
Cell cycle analysis
Comet assay
Gene expression
Micronucleus test
Rubus rosifolius toxicity
topic Apoptosis analysis
Cell cycle analysis
Comet assay
Gene expression
Micronucleus test
Rubus rosifolius toxicity
description Rubus rosifolius, popularly known as “red mulberry”, is a common medicinal plant in southern Brazil and is used as an antidiarrheal, analgesic, antimicrobial and antihypertensive, and to treat stomach diseases. The aim of this study was to analyze the R. rosifolius stem extract (RrSE) for possible in vitro cytotoxic and genotoxic effects, using the comet assay and the micronucleus test to assess genotoxicity, and flow cytometry to assess the impact on the cell cycle and apoptosis in HepG2/C3A cells, in addition to evaluating the expression of genes linked to the induction of DNA damage, cell cycle, apoptosis and metabolism of xenobiotics. The MTT assay observed no cytotoxic effects at concentrations between 0.01 and 100 μg/mL of the extract. However, genotoxic effects occurred in treatments with the extract from a 1 μg/mL concentration. Flow cytometry analysis revealed a significant increase in cells in the G2/M phase after treatment with 10 μg/mL, a decrease in cells in the G0/G1 phase in the treatment with 100 μg/mL, and a significant increase in total apoptotic cells. In the gene expression analysis, an increase in the CYP1A2 xenobiotics metabolizing gene expression was observed. Despite the promising pharmacological effects of R. rosifolius, the results revealed that the RrSE has genotoxic effect and induces apoptosis in HepG2/C3A cells, indicating danger in using this plant extract by humans.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T15:13:11Z
2023-07-29T15:13:11Z
2023-02-01
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.2022.105485
Toxicology in Vitro, v. 86.
1879-3177
0887-2333
http://hdl.handle.net/11449/249331
10.1016/j.tiv.2022.105485
2-s2.0-85141279142
url http://dx.doi.org/10.1016/j.tiv.2022.105485
http://hdl.handle.net/11449/249331
identifier_str_mv Toxicology in Vitro, v. 86.
1879-3177
0887-2333
10.1016/j.tiv.2022.105485
2-s2.0-85141279142
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxicology in Vitro
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
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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