BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 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/10.1590/1678-9199-JVATITD-1476-18 http://hdl.handle.net/11449/185527 |
Resumo: | Background: The use of animal venoms and their toxins as material sources for biotechnological applications has received much attention from the pharmaceutical industry. L-amino acid oxidases from snake venoms (SV-LAAOs) have demonstrated innumerous biological effects and pharmacological potential against different cancer types. Hepatocellular carcinoma has increased worldwide, and the aberrant DNA methylation of liver cells is a common mechanism to promote hepatic tumorigenesis. Moreover, tumor microenvironment plays a major role in neoplastic transformation. To elucidate the molecular mechanisms responsible for the cytotoxic effects of SV-LAAO in human cancer cells, this study aimed to evaluate the cytotoxicity and the alterations in DNA methylation profiler in the promoter regions of cell-cycle genes induced by BjussuLAAO-II, an LAAO from Bothrops jaracussu venom, in human hepatocellular carcinoma (HepG2) cells in monoculture and co-culture with endothelial (HUVEC) cells. Methods: BjussuLAAO-II concentrations were 0.25, 0.50, 1.00 and 5.00 mu g/mL. Cell viability was assessed by MTT assay and DNA methylation of the promoter regions of 22 cell-cycle genes by EpiTect Methyl II PCR array. Results: BjussuLAAO-II decreased the cell viability of HepG2 cells in monoculture at all concentrations tested. In co-culture, 1.00 and 5.00 mu g/mL induced cytotoxicity (p < 0.05). BjussuLAAO-II increased the methylation of CCND1 and decreased the methylation of CDKN1A in monoculture and GADD45A in both cell-culture models (p < 0.05). Conclusion: Data showed BjussuLAAO-II induced cytotoxicity and altered DNA methylation of the promoter regions of cell-cycle genes in HepG2 cells in monoculture and co-culture models. We suggested the analysis of DNA methylation profile of GADD45A as a potential biomarker of the cell cycle effects of BjussuLAAO-II in cancer cells. The tumor microenvironment should be considered to comprise part of biotechnological strategies during the development of snake-toxin-based novel drugs. |
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BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cellssnake venomepigeneticsGADD45ACCND1CDKN1ABackground: The use of animal venoms and their toxins as material sources for biotechnological applications has received much attention from the pharmaceutical industry. L-amino acid oxidases from snake venoms (SV-LAAOs) have demonstrated innumerous biological effects and pharmacological potential against different cancer types. Hepatocellular carcinoma has increased worldwide, and the aberrant DNA methylation of liver cells is a common mechanism to promote hepatic tumorigenesis. Moreover, tumor microenvironment plays a major role in neoplastic transformation. To elucidate the molecular mechanisms responsible for the cytotoxic effects of SV-LAAO in human cancer cells, this study aimed to evaluate the cytotoxicity and the alterations in DNA methylation profiler in the promoter regions of cell-cycle genes induced by BjussuLAAO-II, an LAAO from Bothrops jaracussu venom, in human hepatocellular carcinoma (HepG2) cells in monoculture and co-culture with endothelial (HUVEC) cells. Methods: BjussuLAAO-II concentrations were 0.25, 0.50, 1.00 and 5.00 mu g/mL. Cell viability was assessed by MTT assay and DNA methylation of the promoter regions of 22 cell-cycle genes by EpiTect Methyl II PCR array. Results: BjussuLAAO-II decreased the cell viability of HepG2 cells in monoculture at all concentrations tested. In co-culture, 1.00 and 5.00 mu g/mL induced cytotoxicity (p < 0.05). BjussuLAAO-II increased the methylation of CCND1 and decreased the methylation of CDKN1A in monoculture and GADD45A in both cell-culture models (p < 0.05). Conclusion: Data showed BjussuLAAO-II induced cytotoxicity and altered DNA methylation of the promoter regions of cell-cycle genes in HepG2 cells in monoculture and co-culture models. We suggested the analysis of DNA methylation profile of GADD45A as a potential biomarker of the cell cycle effects of BjussuLAAO-II in cancer cells. The tumor microenvironment should be considered to comprise part of biotechnological strategies during the development of snake-toxin-based novel drugs.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)Research Support Center on Animal Toxins (NAP-TOXAN-USP, Brazil)PRONEXUniv Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, SP, BrazilUniv Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP, BrazilSao Paulo State Univ UNESP, Ctr Study Venoms & Venomous Anim CEVAP, Botucatu, SP, BrazilSao Paulo State Univ UNESP, Ctr Study Venoms & Venomous Anim CEVAP, Botucatu, SP, BrazilCAPES: 3/2016CAPES: 0722/2017CAPES: 88881.142062/2017-01CAPES: 18/2018CAPES: 404770/2018-5FAPESP: 2011/23236-4CAPES: 001PRONEX: 01.09.0447.00/CT-INFRA2008PRONEX: 228.524BmcUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Thomazela Machado, Ana RitaAissa, Alexandre FerroRibeiro, Diego LuisFerreira, Rui Seabra [UNESP]Sampaio, Suely VilelaGreggi Antunes, Lusania Maria2019-10-04T12:36:08Z2019-10-04T12:36:08Z2019-03-11info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9application/pdfhttp://dx.doi.org/10.1590/1678-9199-JVATITD-1476-18Journal Of Venomous Animals And Toxins Including Tropical Diseases. London: Bmc, v. 25, 9 p., 2019.1678-9199http://hdl.handle.net/11449/18552710.1590/1678-9199-JVATITD-1476-18S1678-91992019000100305WOS:000460976300001S1678-91992019000100305.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal Of Venomous Animals And Toxins Including Tropical Diseasesinfo:eu-repo/semantics/openAccess2024-04-11T15:28:17Zoai:repositorio.unesp.br:11449/185527Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-04-11T15:28:17Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells |
title |
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells |
spellingShingle |
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells Thomazela Machado, Ana Rita snake venom epigenetics GADD45A CCND1 CDKN1A |
title_short |
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells |
title_full |
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells |
title_fullStr |
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells |
title_full_unstemmed |
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells |
title_sort |
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells |
author |
Thomazela Machado, Ana Rita |
author_facet |
Thomazela Machado, Ana Rita Aissa, Alexandre Ferro Ribeiro, Diego Luis Ferreira, Rui Seabra [UNESP] Sampaio, Suely Vilela Greggi Antunes, Lusania Maria |
author_role |
author |
author2 |
Aissa, Alexandre Ferro Ribeiro, Diego Luis Ferreira, Rui Seabra [UNESP] Sampaio, Suely Vilela Greggi Antunes, Lusania Maria |
author2_role |
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 |
Thomazela Machado, Ana Rita Aissa, Alexandre Ferro Ribeiro, Diego Luis Ferreira, Rui Seabra [UNESP] Sampaio, Suely Vilela Greggi Antunes, Lusania Maria |
dc.subject.por.fl_str_mv |
snake venom epigenetics GADD45A CCND1 CDKN1A |
topic |
snake venom epigenetics GADD45A CCND1 CDKN1A |
description |
Background: The use of animal venoms and their toxins as material sources for biotechnological applications has received much attention from the pharmaceutical industry. L-amino acid oxidases from snake venoms (SV-LAAOs) have demonstrated innumerous biological effects and pharmacological potential against different cancer types. Hepatocellular carcinoma has increased worldwide, and the aberrant DNA methylation of liver cells is a common mechanism to promote hepatic tumorigenesis. Moreover, tumor microenvironment plays a major role in neoplastic transformation. To elucidate the molecular mechanisms responsible for the cytotoxic effects of SV-LAAO in human cancer cells, this study aimed to evaluate the cytotoxicity and the alterations in DNA methylation profiler in the promoter regions of cell-cycle genes induced by BjussuLAAO-II, an LAAO from Bothrops jaracussu venom, in human hepatocellular carcinoma (HepG2) cells in monoculture and co-culture with endothelial (HUVEC) cells. Methods: BjussuLAAO-II concentrations were 0.25, 0.50, 1.00 and 5.00 mu g/mL. Cell viability was assessed by MTT assay and DNA methylation of the promoter regions of 22 cell-cycle genes by EpiTect Methyl II PCR array. Results: BjussuLAAO-II decreased the cell viability of HepG2 cells in monoculture at all concentrations tested. In co-culture, 1.00 and 5.00 mu g/mL induced cytotoxicity (p < 0.05). BjussuLAAO-II increased the methylation of CCND1 and decreased the methylation of CDKN1A in monoculture and GADD45A in both cell-culture models (p < 0.05). Conclusion: Data showed BjussuLAAO-II induced cytotoxicity and altered DNA methylation of the promoter regions of cell-cycle genes in HepG2 cells in monoculture and co-culture models. We suggested the analysis of DNA methylation profile of GADD45A as a potential biomarker of the cell cycle effects of BjussuLAAO-II in cancer cells. The tumor microenvironment should be considered to comprise part of biotechnological strategies during the development of snake-toxin-based novel drugs. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-04T12:36:08Z 2019-10-04T12:36:08Z 2019-03-11 |
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/10.1590/1678-9199-JVATITD-1476-18 Journal Of Venomous Animals And Toxins Including Tropical Diseases. London: Bmc, v. 25, 9 p., 2019. 1678-9199 http://hdl.handle.net/11449/185527 10.1590/1678-9199-JVATITD-1476-18 S1678-91992019000100305 WOS:000460976300001 S1678-91992019000100305.pdf |
url |
http://dx.doi.org/10.1590/1678-9199-JVATITD-1476-18 http://hdl.handle.net/11449/185527 |
identifier_str_mv |
Journal Of Venomous Animals And Toxins Including Tropical Diseases. London: Bmc, v. 25, 9 p., 2019. 1678-9199 10.1590/1678-9199-JVATITD-1476-18 S1678-91992019000100305 WOS:000460976300001 S1678-91992019000100305.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal Of Venomous Animals And Toxins Including Tropical Diseases |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
9 application/pdf |
dc.publisher.none.fl_str_mv |
Bmc |
publisher.none.fl_str_mv |
Bmc |
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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1799964769805926400 |