C7a, a biphosphinic cyclopalladated compound, efficiently controls the development of a patient-derived xenograft model of adult T cell leukemia/lymphoma.

dc.creatorCorrea, Ana Beatriz Guimarães
dc.creatorCrawford, Lindsey B
dc.creatorFigueiredo, Carlos R
dc.creatorGimenes, Karina Panizzi
dc.creatorPinto, Lorena Ana
dc.creatorGrassi, Maria Fernanda Rios
dc.creatorFeuer, Gerold
dc.creatorTravassos, Luiz Rodolpho
dc.creatorCaires, Antonio Carlos Fávero
dc.creatorRodrigues, Elaine G
dc.creatorMarriott, Susan J
dc.date2014-10-03T18:50:40Z
dc.date2014-10-03T18:50:40Z
dc.date2011
dc.date.accessioned2023-09-26T21:30:59Z
dc.date.available2023-09-26T21:30:59Z
dc.identifierCORREA, A. B. G. et al. C7a, a biphosphinic cyclopalladated compound, efficiently controls the development of a patient-derived xenograft model of adult T cell leukemia/lymphoma. Viruses, v. 3, n. 7, p. 1041-1058, 2011.
dc.identifier1999-4915
dc.identifier10.3390/v3071041
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/8497
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8872664
dc.descriptionAdult T-cell leukemia/lymphoma (ATLL) is a highly aggressive disease that occurs in individuals infected with the human T lymphotropic virus type 1 (HTLV-1). Patients with aggressive ATLL have a poor prognosis because the leukemic cells are resistant to conventional chemotherapy. We have investigated the therapeutic efficacy of a biphosphinic cyclopalladated complex {Pd(2) [S(-)C(2), N-dmpa](2) (µ-dppe)Cl(2)}, termed C7a, in a patient-derived xenograft model of ATLL, and investigated the mechanism of C7a action in HTLV-1-positive and negative transformed T cell lines in vitro. In vivo survival studies in immunocompromised mice inoculated with human RV-ATL cells and intraperitoneally treated with C7a led to significantly increased survival of the treated mice. We investigated the mechanism of C7a activity in vitro and found that it induced mitochondrial release of cytochrome c, caspase activation, nuclear condensation and DNA degradation. These results suggest that C7a triggers apoptotic cell death in both HTLV-1 infected and uninfected human transformed T-cell lines. Significantly, C7a was not cytotoxic to peripheral blood mononuclear cells (PBMC) from healthy donors and HTLV-1-infected individuals. C7a inhibited more than 60% of the ex vivo spontaneous proliferation of PBMC from HTLV-1-infected individuals. These results support a potential therapeutic role for C7a in both ATLL and HTLV-1-negative T-cell lymphomas.
dc.formatapplication/pdf
dc.languageeng
dc.publisherMDPI
dc.rightsopen access
dc.subjectCyclopalladated compound
dc.subjectHTLV-1
dc.subjectATLL
dc.subjectChemotherapy
dc.subjectXenograft model
dc.subjectApoptosis
dc.subjectApoptose/efeitos de drogas
dc.subjectComplexos de Coordenação/farmacologia
dc.subjectVírus 1 Linfotrópico T Humano/crescimento & desenvolvimento
dc.subjectLeucemia-Linfoma de Células T do Adulto/quimioterapia
dc.subjectPaládio/farmacologia
dc.subjectFeniramina/análogos & derivados
dc.subjectAnimais
dc.subjectLinhagem Celular Transformada
dc.subjectSobrevivência Celular/efeitos de drogas
dc.subjectCitocromos c/metabolismo
dc.subjectCitometria de Fluxo
dc.subjectHumanos
dc.subjectLeucemia-Linfoma de Células T do Adulto/virologia
dc.subjectCamundongos
dc.subjectCamundongos SCID
dc.subjectFeniramina/farmacologia
dc.subjectOrganismos Livres de Patógenos Específicos
dc.subjectEnsaios Antitumorais Modelo de Xenoenxerto
dc.titleC7a, a biphosphinic cyclopalladated compound, efficiently controls the development of a patient-derived xenograft model of adult T cell leukemia/lymphoma.
dc.typeArticle


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