Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.ijbiomac.2019.01.059 http://hdl.handle.net/11449/188647 |
Resumo: | Hepatocellular carcinoma incidence rates have increased worldwide, which encouraged the development of new chemotherapeutic drugs. L-Amino acid oxidases from snake venoms are cytotoxic towards human tumor cells in in vitro monoculture systems, which do not simulate the tumor microenvironment. We examined the antitumor potential of BjussuLAAO-II, an L-amino acid oxidase from Bothrops jararacussu venom, in hepatocarcinoma cells (HepG2) in monoculture and co-culture with human umbilical vein endothelial cells (HUVEC) in vitro. All the concentrations tested (0.25–5.00 μg/mL) were cytotoxic (MTT and clonogenic survival assays) towards HepG2 and HUVEC cells in monoculture, and increased oxidative stress by 2′,7′-dichlorofluorescin diacetate fluorescence assay. Only 1.00 and 5.00 μg/mL exerted these effects in HepG2 cells co-cultured with HUVEC cells, and were genotoxic (comet assay) to HUVEC cells in monoculture. BjussuLAAO-II at 5.00 μg/mL induced DNA, but not chromosomal damage (micronucleus assay) in HepG2 cells in mono- and co-culture. The cytotoxicity and genotoxicity was more pronounced in monoculture, indicating that the tumor microenvironment influences the cellular response. BjussuLAAO-II caused cell death and DNA damage in HepG2 cells in vitro by inducing oxidative stress. Therefore, BjussuLAAO-II is a promising molecule for the development of new antitumor drugs. |
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Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cellsMicronucleusSnake venomTumor microenvironmentHepatocellular carcinoma incidence rates have increased worldwide, which encouraged the development of new chemotherapeutic drugs. L-Amino acid oxidases from snake venoms are cytotoxic towards human tumor cells in in vitro monoculture systems, which do not simulate the tumor microenvironment. We examined the antitumor potential of BjussuLAAO-II, an L-amino acid oxidase from Bothrops jararacussu venom, in hepatocarcinoma cells (HepG2) in monoculture and co-culture with human umbilical vein endothelial cells (HUVEC) in vitro. All the concentrations tested (0.25–5.00 μg/mL) were cytotoxic (MTT and clonogenic survival assays) towards HepG2 and HUVEC cells in monoculture, and increased oxidative stress by 2′,7′-dichlorofluorescin diacetate fluorescence assay. Only 1.00 and 5.00 μg/mL exerted these effects in HepG2 cells co-cultured with HUVEC cells, and were genotoxic (comet assay) to HUVEC cells in monoculture. BjussuLAAO-II at 5.00 μg/mL induced DNA, but not chromosomal damage (micronucleus assay) in HepG2 cells in mono- and co-culture. The cytotoxicity and genotoxicity was more pronounced in monoculture, indicating that the tumor microenvironment influences the cellular response. BjussuLAAO-II caused cell death and DNA damage in HepG2 cells in vitro by inducing oxidative stress. Therefore, BjussuLAAO-II is a promising molecule for the development of new antitumor drugs.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Núcleo de Apoio à Pesquisa em Toxinas Animais, Universidade de São PauloDepartment of Clinical Analysis Toxicology and Food Sciences School of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo - USPDepartment of Genetics Ribeirão Preto Medical School University of São Paulo - USPCenter for the Study of Venoms and Venomous Animals (CEVAP) São Paulo State University - UNESPCenter for the Study of Venoms and Venomous Animals (CEVAP) São Paulo State University - UNESPFAPESP: 2011/23236-4Universidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Machado, A. R.T.Aissa, A. F.Ribeiro, D. L.Costa, T. R.Ferreira, R. S. [UNESP]Sampaio, S. V.Antunes, L. M.G.2019-10-06T16:14:47Z2019-10-06T16:14:47Z2019-04-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article425-432http://dx.doi.org/10.1016/j.ijbiomac.2019.01.059International Journal of Biological Macromolecules, v. 127, p. 425-432.1879-00030141-8130http://hdl.handle.net/11449/18864710.1016/j.ijbiomac.2019.01.0592-s2.0-85060309886Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Biological Macromoleculesinfo:eu-repo/semantics/openAccess2024-04-11T15:28:26Zoai:repositorio.unesp.br:11449/188647Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-04-11T15:28:26Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells |
title |
Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells |
spellingShingle |
Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells Machado, A. R.T. Micronucleus Snake venom Tumor microenvironment |
title_short |
Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells |
title_full |
Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells |
title_fullStr |
Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells |
title_full_unstemmed |
Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells |
title_sort |
Cytotoxic, genotoxic, and oxidative stress-inducing effect of an L-amino acid oxidase isolated from Bothrops jararacussu venom in a co-culture model of HepG2 and HUVEC cells |
author |
Machado, A. R.T. |
author_facet |
Machado, A. R.T. Aissa, A. F. Ribeiro, D. L. Costa, T. R. Ferreira, R. S. [UNESP] Sampaio, S. V. Antunes, L. M.G. |
author_role |
author |
author2 |
Aissa, A. F. Ribeiro, D. L. Costa, T. R. Ferreira, R. S. [UNESP] Sampaio, S. V. Antunes, L. M.G. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Machado, A. R.T. Aissa, A. F. Ribeiro, D. L. Costa, T. R. Ferreira, R. S. [UNESP] Sampaio, S. V. Antunes, L. M.G. |
dc.subject.por.fl_str_mv |
Micronucleus Snake venom Tumor microenvironment |
topic |
Micronucleus Snake venom Tumor microenvironment |
description |
Hepatocellular carcinoma incidence rates have increased worldwide, which encouraged the development of new chemotherapeutic drugs. L-Amino acid oxidases from snake venoms are cytotoxic towards human tumor cells in in vitro monoculture systems, which do not simulate the tumor microenvironment. We examined the antitumor potential of BjussuLAAO-II, an L-amino acid oxidase from Bothrops jararacussu venom, in hepatocarcinoma cells (HepG2) in monoculture and co-culture with human umbilical vein endothelial cells (HUVEC) in vitro. All the concentrations tested (0.25–5.00 μg/mL) were cytotoxic (MTT and clonogenic survival assays) towards HepG2 and HUVEC cells in monoculture, and increased oxidative stress by 2′,7′-dichlorofluorescin diacetate fluorescence assay. Only 1.00 and 5.00 μg/mL exerted these effects in HepG2 cells co-cultured with HUVEC cells, and were genotoxic (comet assay) to HUVEC cells in monoculture. BjussuLAAO-II at 5.00 μg/mL induced DNA, but not chromosomal damage (micronucleus assay) in HepG2 cells in mono- and co-culture. The cytotoxicity and genotoxicity was more pronounced in monoculture, indicating that the tumor microenvironment influences the cellular response. BjussuLAAO-II caused cell death and DNA damage in HepG2 cells in vitro by inducing oxidative stress. Therefore, BjussuLAAO-II is a promising molecule for the development of new antitumor drugs. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-06T16:14:47Z 2019-10-06T16:14:47Z 2019-04-15 |
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.ijbiomac.2019.01.059 International Journal of Biological Macromolecules, v. 127, p. 425-432. 1879-0003 0141-8130 http://hdl.handle.net/11449/188647 10.1016/j.ijbiomac.2019.01.059 2-s2.0-85060309886 |
url |
http://dx.doi.org/10.1016/j.ijbiomac.2019.01.059 http://hdl.handle.net/11449/188647 |
identifier_str_mv |
International Journal of Biological Macromolecules, v. 127, p. 425-432. 1879-0003 0141-8130 10.1016/j.ijbiomac.2019.01.059 2-s2.0-85060309886 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Biological Macromolecules |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
425-432 |
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 |
|
_version_ |
1799965568024969216 |