Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8497
Title: C7a, a biphosphinic cyclopalladated compound, efficiently controls the development of a patient-derived xenograft model of adult T cell leukemia/lymphoma.
Authors: Correa, Ana Beatriz Guimarães
Crawford, Lindsey B
Figueiredo, Carlos R
Gimenes, Karina Panizzi
Pinto, Lorena Ana
Grassi, Maria Fernanda Rios
Feuer, Gerold
Travassos, Luiz Rodolpho
Caires, Antonio Carlos Fávero
Rodrigues, Elaine G
Marriott, Susan J
Affilliation: Universidade Federal de São Paulo. UNIFESP-EPM. Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil
SUNY Upstate Medical University. Syracuse Department of Microbiology and Immunology. New York, USA
Universidade Federal de São Paulo. UNIFESP-EPM. Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil
Universidade Federal de São Paulo. UNIFESP-EPM. Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil
Humurine Technologies. Arrow Highway, La Verne, USA
Universidade Federal de São Paulo. UNIFESP-EPM. Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil
Universidade de Mogi de Cruzes. Centro Interdisciplinar de Investigação Bioquímica. Mogi das Cruzes, SP, Brasil
Universidade Federal de São Paulo. UNIFESP-EPM. Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil
Baylor College of Medicine. Department of Molecular Virology and Microbiology. Houston Texas, USA
Abstract: Adult 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.
Keywords: Cyclopalladated compound
HTLV-1
ATLL
Chemotherapy
Xenograft model
Apoptosis
DeCS: Apoptose/efeitos de drogas
Complexos de Coordenação/farmacologia
Vírus 1 Linfotrópico T Humano/crescimento & desenvolvimento
Leucemia-Linfoma de Células T do Adulto/quimioterapia
Paládio/farmacologia
Feniramina/análogos & derivados
Animais
Linhagem Celular Transformada
Sobrevivência Celular/efeitos de drogas
Citocromos c/metabolismo
Citometria de Fluxo
Humanos
Leucemia-Linfoma de Células T do Adulto/virologia
Camundongos
Camundongos SCID
Feniramina/farmacologia
Organismos Livres de Patógenos Específicos
Ensaios Antitumorais Modelo de Xenoenxerto
Issue Date: 2011
Publisher: MDPI
Citation: CORREA, 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.
ISSN: 1999-4915
10.3390/v3071041
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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