(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone inhibits tubulin polymerization, induces G2/M arrest, and triggers apoptosis in human leukemia HL-60 cells.

dc.creatorMagalhães, Hemerson Iury Ferreira
dc.creatorWilke, Diego Veras
dc.creatorBezerra, Daniel Pereira
dc.creatorCavalcanti, Bruno C
dc.creatorRotta, Rodrigo
dc.creatorLima, Dênis Pires de
dc.creatorBeatriz, Adilson
dc.creatorMoraes, Manoel O
dc.creatorDiniz Filho, Jairo
dc.creatorPessoa, Claudia
dc.date2014-11-06T17:28:58Z
dc.date2014-11-06T17:28:58Z
dc.date2013
dc.date.accessioned2023-09-26T22:20:30Z
dc.date.available2023-09-26T22:20:30Z
dc.identifierMAGALHÃES, H. I. F. et al. (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone inhibits tubulin polymerization, induces G2/M arrest, and triggers apoptosis in human leukemia HL-60 cells. Toxicology Applied Pharmacology, v. 272, n. 1, p. 117-126, 2013.
dc.identifier1096-0333
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/8744
dc.identifierdx.doi.org/10.1016/j.taap.2013.06.001
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8878081
dc.description(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a known cytotoxic compound belonging to the phenstatin family. However, the exact mechanism of action of PHT-induced cell death remains to be determined. The aim of this study was to investigate the mechanisms underlying PHT-induced cytotoxicity. We found that PHT displayed potent cytotoxicity in different tumor cell lines, showing IC50 values in the nanomolar range. Cell cycle arrest in G2/M phase along with the augmented metaphase cells was found. Cells treated with PHT also showed typical hallmarks of apoptosis such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of the caspase 3/7 and 8 activation, loss of mitochondrial membrane potential, and internucleosomal DNA fragmentation without affecting membrane integrity. Studies conducted with isolated tubulin and docking models confirmed that PHT binds to the colchicine site and interferes in the polymerization of microtubules. These results demonstrated that PHT inhibits tubulin polymerization, arrests cancer cells in G2/M phase of the cell cycle, and induces their apoptosis, exhibiting promising anticancer therapeutic potential.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier Inc
dc.rightsopen access
dc.subjectPhenstatins
dc.subjectTubulin inhibitors
dc.subjectApoptosis
dc.subjectCaspase activation
dc.subjectApoptose/efeitos de drogas
dc.subjectBenzofenonas/farmacologia
dc.subjectDivisão Celular/efeitos de drogas
dc.subjectFase G2/efeitos de drogas
dc.subjectModuladores de Tubulina
dc.subjectTubulina (Proteína)/biossíntese
dc.subjectAnexinas/metabolismo
dc.subjectAntimetabólitos/uso diagnóstico
dc.subjectBenzofenonas/síntese química
dc.subjectBromodesoxiuridina/uso diagnóstico
dc.subjectCaspases/metabolismo
dc.subjectMorte Celular/efeitos de drogas
dc.subjectMembrana Celular/fisiologia
dc.subjectSobrevivência Celular/efeitos de drogas
dc.subjectCorantes
dc.subjectEnsaio Cometa
dc.subjectFragmentação do DNA/efeitos de drogas
dc.subjectCélulas HL-60
dc.subjectHumanos
dc.subjectPotencial da Membrana Mitocondrial/efeitos de drogas
dc.subjectModelos moleculares
dc.title(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone inhibits tubulin polymerization, induces G2/M arrest, and triggers apoptosis in human leukemia HL-60 cells.
dc.typeArticle


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