Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression

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dc.creatorAndrade, Francyelli Mariana dos Santos Mello
dc.creatorCosta, Wanderson Lucas da
dc.creatorPires, Wanessa Carvalho
dc.creatorPereira, Flávia de Castro
dc.creatorCardoso, Clever Gomes
dc.creatorLino Junior, Ruy de Souza
dc.creatorChavarria Irusta, Vicente Raul
dc.creatorCarneiro, Cristiene Costa
dc.creatorReis, Paulo Roberto de Melo
dc.creatorCastro, Carlos Henrique de
dc.date.accessioned2025-04-14T12:26:32Z
dc.date.available2025-04-14T12:26:32Z
dc.date.issued2017
dc.description.abstractPeritoneal carcinomatosis is considered as a potentially lethal clinical condition, and the therapeutic options are limited. The antitumor effectiveness of the [Ru(l-Met)(bipy)(dppb)]PF6 (1) and the [Ru(l-Trp)(bipy)(dppb)]PF6 (2) complexes were evaluated in the peritoneal carcinomatosis model, Ehrlich ascites carcinoma–bearing Swiss mice. This is the first study that evaluated the effect of Ru(II)/amino acid complexes for antitumor activity in vivo. Complexes 1 and 2 (2 and 6mgkg−1) showed tumor growth inhibition ranging from moderate to high. The mean survival time of animal groups treated with complexes 1 and 2 was higher than in the negative and vehicle control groups. The induction of Ehrlich ascites carcinoma in mice led to alterations in hematological and biochemical parameters, and not the treatment with complexes 1 and 2. The treatment of Ehrlich ascites carcinoma–bearing mice with complexes 1 and 2 increased the number of Annexin V positive cells and cleaved caspase-3 levels and induced changes in the cell morphology and in the cell cycle phases by induction of sub-G1 and G0/G1 cell cycle arrest. In addition, these complexes reduce angiogenesis induced by Ehrlich ascites carcinoma cells in chick embryo chorioallantoic membrane model. The treatment with the LAT1 inhibitor decreased the sensitivity of the Ehrlich ascites carcinoma cells to complexes 1 and 2 in vitro—which suggests that the LAT1 could be related to the mechanism of action of amino acid/ruthenium(II) complexes, consequently decreasing the glucose uptake. Therefore, these complexes could be used to reduce tumor growth and increase mean survival time with less toxicity than cisplatin. Besides, these complexes induce apoptosis by combination of different mechanism of action.
dc.identifier.citationMELLO-ANDRADE, Francyelli et al. Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression. Tumor Biology, Tokyo, v. 39, n. 10, e101042831769593, 2017. DOI: 10.1177/1010428317695933. Disponível em: https://journals.sagepub.com/doi/full/10.1177/1010428317695933?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org. Acesso em: 10 abr. 2025.
dc.identifier.doi10.1177/1010428317695933
dc.identifier.issn1010-4283
dc.identifier.issne- 1423-0380
dc.identifier.urihttp://repositorio.bc.ufg.br//handle/ri/27259
dc.language.isoeng
dc.publisher.countryOutros
dc.publisher.departmentInstituto de Patologia Tropical e Saúde Pública - IPTSP (RMG)
dc.rightsAcesso Aberto
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectRuthenium
dc.subjectPeritoneal carcinomatosis
dc.subjectAntitumor activity
dc.subjectAngiogenesis
dc.subjectLAT1
dc.subjectApoptosis
dc.titleAntitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression
dc.typeArtigo

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