Xylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells

dc.creatorSantos, Luciano de Souza
dc.creatorSilva, Valdenizia Rodrigues
dc.creatorMenezes, Leociley Rocha Alencar
dc.creatorSoares, Milena Botelho Pereira
dc.creatorCosta, Emmanoel Vilaça
dc.creatorBezerra, Daniel Pereira
dc.date2018-04-23T19:01:01Z
dc.date2018-04-23T19:01:01Z
dc.date2017
dc.date.accessioned2023-09-26T20:39:16Z
dc.date.available2023-09-26T20:39:16Z
dc.identifierSANTOS, L. S. et al. Xylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells. Oxidative Medicine and Cellular Longevity, ID 7126872, 2017.
dc.identifier1942-0900
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/26043
dc.identifier10.1155/2017/7126872
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8861395
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB), and Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM).
dc.descriptionXylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells. In this study, the underlying mechanism of xylopine cytotoxicity was assessed in human colon carcinoma HCT116 cells. Xylopine displayed potent cytotoxicity in different cancer cell lines in monolayer cultures and in a 3D model of cancer multicellular spheroids formed from HCT116 cells. Typical morphology of apoptosis, cell cycle arrest in the G2/M phase, increased internucleosomal DNA fragmentation, loss of the mitochondrial transmembrane potential, and increased phosphatidylserine externalization and caspase-3 activation were observed in xylopine-treated HCT116 cells. Moreover, pretreatment with a caspase-3 inhibitor (Z-DEVD-FMK), but not with a p53 inhibitor (cyclic pifithrin-α), reduced xylopine-induced apoptosis, indicating induction of caspase-mediated apoptosis by the p53-independent pathway. Treatment with xylopine also caused an increase in the production of reactive oxygen/nitrogen species (ROS/RNS), including hydrogen peroxide and nitric oxide, but not superoxide anion, and reduced glutathione levels were decreased in xylopine-treated HCT116 cells. Application of the antioxidant N-acetylcysteine reduced the ROS levels and xylopine-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. In conclusion, xylopine has potent cytotoxicity to different cancer cell lines and is able to induce oxidative stress and G2/M phase arrest, triggering caspase-mediated apoptosis by the p53-independent pathway in HCT116 cells.
dc.formatapplication/pdf
dc.languageeng
dc.publisherHindawi Publishing Corporation
dc.rightsopen access
dc.subjectEstresse oxidativo
dc.subjectApoptose
dc.subjectCaspases
dc.subjectAlcalóides
dc.subjectCélulas HCT116
dc.subjectCarcinoma
dc.subjectSaúde pública
dc.subjectNeoplasia do colon
dc.subjectOxidative Stress
dc.subjectApoptosis
dc.subjectCaspase
dc.subjectAlkaloid
dc.subjectHCT116 Cells
dc.subjectCarcinoma
dc.subjectPublic health
dc.subjectColon neoplasm
dc.titleXylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells
dc.typeArticle


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