Heterobimetallic Ru(ii)/Fe(ii) complexes as potent anticancer agents against breast cancer cells, inducing apoptosis through multiple targets

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dc.contributor.authorMundim Guedes, Adriana Pereira
dc.contributor.authorMello-Andrade, Francyelli
dc.contributor.authorPires, Wanessa Carvalho
dc.contributor.authorMontes de Sousa, Maria Alice
dc.contributor.authorFaustino da Silva, Paula Francinete
dc.contributor.authorCamargo, Mariana S. de
dc.contributor.authorGemeiner, Hendryk [UNESP]
dc.contributor.authorAmauri, Menegario A. [UNESP]
dc.contributor.authorCardoso, Clever Gomes
dc.contributor.authorMelo Reis, Paulo Roberto de
dc.contributor.authorSilveira-Lacerda, Elisangela de Paula
dc.contributor.authorBatista, Alzir A.
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversidade Federal de Goiás (UFG)
dc.contributor.institutionFed Inst Educ Sci & Technol Goias
dc.contributor.institutionPontifical Catholic Univ Goias
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2020-12-10T17:36:59Z
dc.date.available2020-12-10T17:36:59Z
dc.date.issued2020-04-01
dc.description.abstractAntimetastatic activity, high selectivity and cytotoxicity for human tumor cell lines make ruthenium(ii) complexes attractive for the development of new chemotherapeutic agents for cancer treatment. In this study, cytotoxic activities and the possible mechanism of cell death induced by three ruthenium complexes were evaluated, [Ru(MIm)(bipy)(dppf)]PF6(1), [RuCl(Im)(bipy)(dppf)]PF6(2) and [Ru(tzdt)(bipy)(dppf)]PF6(3). The results showed high cytotoxicity and selectivity indexes for the human triple-negative breast tumor cell line (MDA-MB-231) with IC(50)value and selectivity index for complex1(IC50= 0.33 +/- 0.03 mu M, SI = 4.48), complex2(IC50= 0.80 +/- 0.06 mu M, SI = 2.31) and complex3(IC50= 0.48 +/- 0.02 mu M, SI = 3.87). The mechanism of cell death induced in MDA-MB-231 cells, after treatment with complexes1-3, indicated apoptosis of the cells as a consequence of the increase in the percentage of cells in the Sub-G1 phase in the cell cycle analysis, characteristic morphological changes and the presence of apoptotic cells labeled with Annexin-V. Multiple targets of action were identified for complexes1and3with an induction of DNA damage in cells treated with complexes1and3, mitochondrial depolarization with a reduction in mitochondrial membrane potential, an increase in reactive oxygen species levels and increased expression levels of caspase 3 and p53. In addition, antimetastatic activities for complexes1and3were observed by inhibition of cell migration by the wound healing assay and Boyden chamber assay, as well as inhibition of angiogenesis caused by MDA-MB-231 tumor cells in the CAM model.en
dc.description.affiliationUniv Fed Sao Carlos, Dept Chem, CP 676, BR-13565905 Sao Carlos, SP, Brazil
dc.description.affiliationUniv Fed Goias, Inst Biol Sci, Dept Genet, BR-74690900 Goiania, Go, Brazil
dc.description.affiliationFed Inst Educ Sci & Technol Goias, Dept Chem, BR-74055110 Goiania, Go, Brazil
dc.description.affiliationPontifical Catholic Univ Goias, Lab Expt & Biotechnol Res, Masters Program Environm Sci & Hlth, Sch Med Sci,Pharmaceut & Biomed Lab, BR-74605010 Goiania, Go, Brazil
dc.description.affiliationSao Paulo State Univ, Ctr Environm Studies, BR-13506900 Rio Claro, SP, Brazil
dc.description.affiliationUniv Fed Goias, Inst Biol Sci, Dept Morphol, BR-74690900 Goiania, Go, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Ctr Environm Studies, BR-13506900 Rio Claro, SP, Brazil
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdCAPES: 001
dc.description.sponsorshipIdFAPESP: 2016/16312-0
dc.format.extent547-561
dc.identifierhttp://dx.doi.org/10.1039/c9mt00272c
dc.identifier.citationMetallomics. Cambridge: Royal Soc Chemistry, v. 12, n. 4, p. 547-561, 2020.
dc.identifier.doi10.1039/c9mt00272c
dc.identifier.issn1756-5901
dc.identifier.urihttp://hdl.handle.net/11449/195507
dc.identifier.wosWOS:000547164400006
dc.language.isoeng
dc.publisherRoyal Soc Chemistry
dc.relation.ispartofMetallomics
dc.sourceWeb of Science
dc.titleHeterobimetallic Ru(ii)/Fe(ii) complexes as potent anticancer agents against breast cancer cells, inducing apoptosis through multiple targetsen
dc.typeArtigo
dcterms.rightsHolderRoyal Soc Chemistry

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