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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Three-dimensional cell culture models for metallodrug testing: induction of apoptosis and phenotypic reversion of breast cancer cells by the trans-[Ru(PPh3)(2)(N,N-dimethyl-N-thiophenyl-thioureato-k(2)O,S)(bipy) ]PF6 complex

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Becceneri, Amanda B. [1] ; Fuzer, Angelina M. [1] ; Plutin, Ana M. [2] ; Batista, Alzir A. [3] ; Lelievre, Sophie A. [4, 5] ; Cominetti, Marcia R. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Fed Sao Carlos, Dept Gerontol, Rod Washington Luis, Km 235, BR-13565905 Sao Carlos - Brazil
[2] Univ La Habana, Fac Quim, Zapata S-N Entre G & Carlitos, Havana 10400 - Cuba
[3] Univ Fed Sao Carlos, Dept Chem, Rod Washington Luis, Km 235, BR-13565905 Sao Carlos, SP - Brazil
[4] Purdue Univ, Dept Basic Med Sci, 625 Harrison St, W Lafayette, IN 47907 - USA
[5] Purdue Univ, Ctr Canc Res, 625 Harrison St, W Lafayette, IN 47907 - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: INORGANIC CHEMISTRY FRONTIERS; v. 7, n. 16, p. 2909-2919, AUG 21 2020.
Citações Web of Science: 4

Many studies have revealed the advantages of using three-dimensional (3D) culture over traditional twodimensional (2D) monolayer techniques. The 3D cell culture models represent biologically relevant approaches to better mimic the tumor organization observed in vivo. These models have high potential for anticancer drug development and screening, for which challenges include tumor cell resistance to treatment and the risk of toxicity for patients. Many anticancer drug candidates do not reach clinical trials as they fail preclinical tests in vivo, although they were promising in 2D cultures. Models from 3D cell cultures are proposed as intermediate screening filters between 2D and in vivo assays. It has been suggested that ruthenium complexes have great potential for breast cancer treatment. Here, we tested the trans{[}Ru(PPh3)(2)(N,N-dimethyl-N-thiophenylthioureato-k(2)O,S)(bipy)]P F6 complex in breast cancer cell lines using different 3D culture techniques, including the embedded, `on top' and disease-on-a-chip (DOC) models that reproduce physical aspects of the tumor microenvironment. The complex had pronounced but distinct cytotoxic effects on tumors cultured in collagen I of appropriate stiffness for the disease stage; the extent of induced apoptosis depends on the preinvasive (S2 cells) and invasive (T4-2 and MDA-MB-231 cells) nature of triple-negative breast cancer models. Remarkably, in the DOC model, which simulates breast ductal architecture, the complex was cytotoxic for T4-2 tumors but had no remarkable effect on the differentiated luminal epithelial S1 cells, demonstrating selectivity against cancer cells. In addition, a lower concentration of the complex abrogated the malignant phenotype of the T4-2 cells with reduction of EGFR, p50 NF kappa B, and beta 1-integrin expression. To the best of our knowledge, this work uniquely demonstrates the effects of a ruthenium complex on the induction of apoptosis and on the phenotypic reversion of tumor cells in 3D cultures. These results warrant moving to in vivo evaluation of this ruthenium complex. (AU)

Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
Beneficiário:Glaucius Oliva
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 14/25121-8 - Atividade Antitumoral e Potencial Mutagênico de Novos Complexos de Rutênio
Beneficiário:Amanda Blanque Becceneri
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 17/20055-5 - Efeitos do complexo de rutênio trans[Ru(ThySMet)(PPh3)2(bipy)]PF6 em células tumorais de mama em cultura tridimensional
Beneficiário:Amanda Blanque Becceneri
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
Processo FAPESP: 15/24940-8 - Avaliação da eficácia de mudanças estruturais do [10]-gingerol em combinação com o quimioterápico doxorubicina para o tratamento de câncer de mama: estudos in vitro e in vivo
Beneficiário:Márcia Regina Cominetti
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/19342-2 - Complexos metalicos com ligantes derivados da lausona e aciltioureas, com potenciais atividades anticancerígenas: estudos in vitro e in vivo
Beneficiário:Alzir Azevedo Batista
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/01287-2 - Triagem de compostos candidatos a novos medicamentos antitumorais por cultura celular tridimensional
Beneficiário:Angelina Maria Fuzer
Linha de fomento: Bolsas no Brasil - Pós-Doutorado