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dc.contributor.authordos Santos Cardoso, Plinio Cerqueira
dc.contributor.authorMachado da Rocha, Carlos Alberto
dc.contributor.authorLeal, Mariana Ferreira [UNIFESP]
dc.contributor.authorBahia, Marcelo de Oliveira
dc.contributor.authorAvila Alcantara, Diego Di Felipe
dc.contributor.authordos Santos, Raquel Alves
dc.contributor.authorGoncalves, Natalia dos Santos
dc.contributor.authorAmbrosio, Sergio Ricardo
dc.contributor.authorCavalcanti, Bruno Coelho
dc.contributor.authorMoreira-Nunes, Caroline Aquino
dc.contributor.authorPessoa, Claudia do O.
dc.contributor.authorRodriguez Burbano, Rommel Mario
dc.identifier.citationBiomedicine & Pharmacotherapy. Paris, v. 89, p. 772-780, 2017.
dc.description.abstractThe goal of our study was to evaluate the effect of kaurenoic acid, obtained from copaiba oil resin, in gastric cancer (GC) and a normal mucosa of stomach (MNP01) cell lines. The compound was tested at concentrations of 2.5, 5, 10, 30 and 60 mu g/mL. Comet and micronucleus assays were used to access its potential genotoxicity in vitro. Moreover, we evaluated the effect of kaurenoic acid in cell cycle progression and in the transcription of genes involved in the control of the cell cycle: MYC, CCND1, BCL2, CASP3, ATM, CHK2 and TP53. Kaurenoic acid induced an increase on cell DNA damage or micronucleus frequencies on GC cell lines in a dose-dependent manner. The GC and MNP01 cell lines entering DNA synthesis and mitosis decreased significantly with kaurenoic acid treatment, and had an increased growth phase compared with non-treated cells. The treatment induced apoptosis (or necrosis) even at a concentration of 2.5 mu g/mL in relation to non-treated cells. GC cell lines presented reduced MYC, CCND1, BCL2 and CASP3 transcription while ATM, CHK2 and TP53 increased in transcription in relation to nontreated cells, especially at a concentration above 10 mu g/mL. The gene transcription in the MNP01 (nontreated non-cancer cell line) was designated as a calibrator for all the GC cell lines. In conclusion, our results showed that kaurenoic acid obtained from Copaifera induces DNA damage and increases the micronuclei frequency in a dose-dependent manner in GC cells, with a significant genotoxicity observed above the concentration of 5 mu g/mL. Moreover, this compound seems to be able to induce cell cycle arrest and apoptosis in GC cells. (C) 2017 Elsevier Masson SAS. All rights reserved.en
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevier
dc.relation.ispartofBiomedicine & Pharmacotherapy
dc.rightsAcesso restrito
dc.subjectCell cycle progressionen
dc.subjectComet assayen
dc.subjectGastric cancer cell linesen
dc.subjectGene transcriptionsen
dc.subjectKaurenoic aciden
dc.titleEffect of diterpenoid kaurenoic acid on genotoxicity and cell cycle progression in gastric cancer cell linesen
dc.description.affiliationFed Univ Para UFPA, Biol Sci Inst, Human Cytogenet Lab, Belem, Para, Brazil
dc.description.affiliationFed Inst Educ Sci & Technol Para IFPA, Av Almirante Barroso,1155 Marco, BR-66093020 Belem, Para, Brazil
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Dept Morphol & Genet, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Franca UNIFRAN, Lab Genet & Mol Biol, Franca, SP, Brazil
dc.description.affiliationUniv Franca UNIFRAN, Lab Biotransformat, Franca, SP, Brazil
dc.description.affiliationFed Univ Ceara UFC, Dept Physiol & Pharmacol, Fortaleza, Ceara, Brazil
dc.description.affiliationFed Univ Ceara UFC, Lab Genet Hemoglobinopathies & Hematol Dis, Fortaleza, Ceara, Brazil
dc.description.affiliationHosp Ophir Loyola, Av Magalhaes Barata 992, BR-66060281 Belem, Para, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Dept Morphol & Genet, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science

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