Biological effects of an oxyphytosterol generated by β-Sitosterol ozonization

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dc.contributorLab. Desenvolvimento e Inovaçãopt_BR
dc.contributorLab. Biologia Molecularpt_BR
dc.contributor.authorTakayasu, Bianca Sayuript_BR
dc.contributor.authorMartins, Igor R.pt_BR
dc.contributor.authorGarnique, Anali M.B.pt_BR
dc.contributor.authorMiyamoto, Sayuript_BR
dc.contributor.authorMachado-Santelli, Gláucia M.pt_BR
dc.contributor.authorOnuki, Janicept_BR
dc.date.accessioned2020-11-04T20:26:06Z-
dc.date.available2020-11-04T20:26:06Z-
dc.date.issued2020pt_BR
dc.identifier.citationTakayasu BS, Martins IR., Garnique AM.B., Miyamoto S, Machado-Santelli GM., Onuki J. Biological effects of an oxyphytosterol generated by β-Sitosterol ozonization. Arch. Biochem. Biophys.. 2020 Oct;696:108654. doi:10.1016/j.abb.2020.108654.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/3299-
dc.description.abstractβ-Sitosterol (βSito) is the most abundant phytosterol found in vegetable oils, grains such as wheat, beans, and corn, and in many phytosterol-enriched foods. It is prone to oxidation by reactive oxygen species, such as ozone, leading to the formation of oxyphytosterols. A better understanding regarding the biological effects and mechanism of action of oxyphytosterols is required since the beneficial and adverse side effects of these compounds on human health remain highly controversial. In this work, we investigated the biological effects of β-Secosterol (βSec), a new oxyphytosterol generated by the reaction of βSito with ozone. Treatment of HepG2 cells with βSito or βSec (0.1–100 μM) for 24, 48, and 72 h induced a dose-dependent reduction of cell viability in the MTT assay, with βSec showing higher efficacy than βSito. However, βSec presented a lower potency than βSito, showing IC50 = 37.32 μM, higher than βSito (IC50 = 0.23 μM) at 48 h. Cell cycle analyses by flow cytometry showed a slight decrease of G1 phase with βSito 0.5 μM, but a significant cell cycle arrest at the G0/G1 phase in the treatment for 48 h with βSec 20 μM (62.69 ± 2.15%, p < 0.05) and βSec 40 μM (66.96 ± 5.39%, p < 0.0001) when compared to control (56.97 ± 2.60%). No suggestion of apoptosis was indicated by flow cytometry data. Also, βSec (20 and 40 μM) reduced the mitotic index. In the analysis with a confocal laser-scanning microscope, no alterations in cell morphology were observed with βSito (0.5 μM). Nevertheless, round-shaped cells, abnormal nuclear morphology with shrinkage, and formation of microtubules clusters were observed in the treatment with βSec, indicating a disruption in the microtubules network organization. N-acetyl-l-cysteine was not able to inhibit any of these cellular effects, indicating a lack of involvement of oxidative stress in the mechanism of action of βSec. Although not further investigated in this study, it was discussed the hypothesis that covalent adduct formation with lysine residues of proteins, could play an important role in the biological effects elicited by βSec. Elucidation of the primary cellular processes induced by βSec provides the essential knowledge to be aware of its potential adverse side effects or therapeutic use of this oxyphytosterol.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipFinanciadora de Estudos e Projetos (FINEP)pt_BR
dc.description.sponsorshipFundação Butantanpt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.format.extent108654pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofArchives of Biochemistry and Biophysicspt_BR
dc.titleBiological effects of an oxyphytosterol generated by β-Sitosterol ozonizationpt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1016/j.abb.2020.108654pt_BR
dc.identifier.urlhttps://doi.org/10.1016/j.abb.2020.108654pt_BR
dc.contributor.externalUniversidade de São Paulo (USP)pt_BR
dc.contributor.externalUniversidade Federal de São Paulo (UNIFESP)pt_BR
dc.identifier.citationvolume696pt_BR
dc.subject.keywordPhytosterolpt_BR
dc.subject.keywordOxyphytosterolspt_BR
dc.subject.keywordβSecpt_BR
dc.subject.keywordCytotoxicitypt_BR
dc.subject.keywordMicrotubulespt_BR
dc.subject.keywordCell cyclept_BR
dc.subject.keywordOzonept_BR
dc.relation.ispartofabbreviatedArch Biochem Biophyspt_BR
dc.identifier.citationabntv. 696, 108654, out. 2020pt_BR
dc.identifier.citationvancouver2020 Oct;696:108654pt_BR
dc.contributor.butantanTakayasu, Bianca Sayuri|:Aluno|:Lab. Desenvolvimento e Inovação|:PrimeiroAutorpt_BR
dc.contributor.butantanOnuki, Janice|:Pesquisador|:Lab. Desenvolvimento e Inovação:Lab. Biologia Molecular|:Autor de correspondênciapt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/07937–8pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2015/17,177–6pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2014/14,801–8pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2019/19,506–8pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦303,464/2017–8pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦484,628/2013–5pt_BR
dc.sponsorship.butantanFinanciadora de Estudos e Projetos (FINEP)¦¦pt_BR
dc.sponsorship.butantanFundação Butantan¦¦pt_BR
dc.sponsorship.butantanCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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item.grantfulltextembargo_29990101-
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