A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway

dc.creatorCarvalho, Nanashara Coelho de
dc.creatorNeves, Sara Parente
dc.creatorDias, Rosane Borges
dc.creatorValverde, Ludmila de Faro
dc.creatorSales, Caroline Brandi Schlaepfer
dc.creatorRocha, Clarissa Araújo Gurgel
dc.creatorSoares, Milena Botelho Pereira
dc.creatorSantos, Edjane Rocha dos
dc.creatorOliveira, Regina Maria Mendes
dc.creatorCarlos, Rose Maria
dc.creatorNogueira, Paulo Cesar de Lima
dc.creatorBezerra, Daniel Pereira
dc.date2018-02-15T14:20:03Z
dc.date2018-02-15T14:20:03Z
dc.date2018
dc.date.accessioned2023-09-26T22:45:27Z
dc.date.available2023-09-26T22:45:27Z
dc.identifierCARVALHO, Nanashara Coelho de et al. A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway. Cell Death and Disease, v. 9, n. 79, p. 2-24, 23 Jan. 2018.
dc.identifier2041-4889
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/24832
dc.identifier10.1038/s41419-017-0104-6
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8882818
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado da Bahia (FAPESB)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionRuthenium-based compounds have gained great interest due to their potent cytotoxicity in cancer cells; however, much of their potential applications remain unexplored. In this paper, we report the synthesis of a novel ruthenium complex with xanthoxylin (RCX) and the investigation of its cellular and molecular action in human hepatocellular carcinoma HepG2 cells. We found that RCX exhibited a potent cytotoxic effect in a panel of cancer cell lines in monolayer cultures and in a 3D model of multicellular cancer spheroids formed from HepG2 cells. This compound is detected at a high concentration in the cell nuclei, induces DNA intercalation and inhibits DNA synthesis, arresting the cell cycle in the S-phase, which is followed by the activation of the caspase-mediated apoptosis pathway in HepG2 cells. Gene expression analysis revealed changes in the expression of genes related to cell cycle control, apoptosis and the MAPK pathway. In addition, RCX induced the phosphorylation of ERK1/2, and pretreatment with U-0126, an MEK inhibitor known to inhibit the activation of ERK1/2, prevented RCX-induced apoptosis. In contrast, pretreatment with a p53 inhibitor (cyclic pifithrin-α) did not prevent RCX-induced apoptosis, indicating the activation of a p53-independent apoptosis pathway. RCX also presented a potent in vivo antitumor effect in C.B-17 SCID mice engrafted with HepG2 cells. Altogether, these results indicate that RCX is a novel anticancer drug candidate.
dc.formatapplication/pdf
dc.languageeng
dc.publisherSpringer Nature
dc.rightsopen access
dc.subjectCompostos de rutênio
dc.subjectCarcinoma
dc.subjectAnticorpos antitumorais
dc.subjectHepatocellular carcinoma
dc.subjectCiclo celular
dc.subjectApoptose
dc.subjectRuthenium complex
dc.subjectCarcinoma
dc.subjectAntitumor antibodies
dc.subjectCell cycle
dc.subjectApoptosis
dc.titleA novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway
dc.typeArticle


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