Navegando por Autor "Barros, Tatiane Martins Barcelos"
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Item Cytotoxic and toxicogenomic effects of silibinin in bladder cancer cells with different TP53 status.(2017) Oliveira, Daiane Teixeira de; Sávio, André Luiz Ventura; Marcondes, João Paulo de Castro; Barros, Tatiane Martins Barcelos; Barbosa, Ludmila Correia; Salvadori, Daisy Maria Fávero; Silva, Glenda Nicioli daSilibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated. Silibinin promoted decreased proliferation and increased late apoptosis in TP53 mutated cells. Increased early apoptosis rates, primary DNA damage, and decrease of cell colonies in the clonogenic survival assay were detected in both RT4 and T24 cell lines. Down-regulation of FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 expression occurred in RT4 cells. Modulation of miR203 was observed in both cell lines. In conclusion, despite the reduction of clone formation in both cell lines, the toxicogenomic effect of silibinin on FRAP/mTOR, AKT2, FGFR3, DNMT1 and miR100 was dependent on the TP53 status. Taken together, the data confirmed the role of silibinin as an antiproliferative compound, whose mechanism of action was related to the TP53 status.Item Efeitos citotóxicos e toxicogenômicos da silibinina em células de câncer de bexiga com diferentes status do gene TP53.(2019) Barros, Tatiane Martins Barcelos; Silva, Glenda Nicioli da; Silva, Glenda Nicioli da; Sabino, Adriano de Paula; Souza, Gustavo Henrique Bianco deA silibinina, um composto natural extraído de frutos e sementes de Silybum marianum, demonstrou propriedades antitumorais em células de câncer de bexiga; no entanto, o papel do gene TP53 nestes efeitos não é claro. Para entender melhor os mecanismos moleculares e antiproliferativos deste composto, células de câncer de bexiga com diferentes status do gene TP53, RT4 (tumor de baixo grau, gene TP53 selvagem), 5637 (grau 2, tumor de alto grau, gene TP53 mutado) e T24 (grau 3, tumor de alto grau, gene TP53 mutado), foram tratadas com silibinina nas concentrações 1; 5; 10; 50; 100 e 150 μM. Vários parâmetros foram avaliados, incluindo citotoxicidade, efeito pró-oxidante, alterações morfológicas, migração celular, progressão do ciclo celular, perfil de metilação global e expressão relativa dos genes HOXB3, c-MYC, PLK1, SMAD4, SRC, HAT, HDAC e RASSF1A. Os resultados mostraram que a silibinina apresentou efeitos citotóxicos e próoxidantes nas três linhagens celulares. A interferência significativa na migração celular e a parada do ciclo celular na fase G2 / M foram observadas em células com o gene TP53 mutado. Além disso, a silibinina induziu hipometilação global de DNA nas células com maior grau de tumor. Para as células TP53 do tipo selvagem, o conteúdo sub-G1 estava presente de forma significativa. Além disso, houve modulação da expressão gênica dos oncogenes responsáveis pelo crescimento celular (SMAD e c-MYC), migração (SRC e HOXB3), cinética do ciclo celular (PLK1), angiogênese (HOXB3) e genes associados a eventos epigenéticos como acetilação de DNA (HAT) e desacetilação (HDAC). Em conclusão, a silibinina inibe a proliferação celular independentemente do status de TP53. Entretanto, os efeitos sobre o ciclo celular, a migração celular e a expressão gênica são dependentes do status de TP53.Item Inhibition of urinary bladder cancer cell proliferation by silibinin.(2020) Barros, Tatiane Martins Barcelos; Lima, Ana Paula Braga; Almeida, Tamires Cunha; Silva, Glenda Nicioli daSilibinin, a natural compound extracted from milk thistle, has demonstrated antitumor properties in urinary bladder cancer cells; however, the role of TP53 gene in these effects is unclear. In order to better understand the molecular and antiproliferative mechanisms of this compound, urinary bladder cancer cells with different TP53 gene status, RT4 (low-grade tumor, wild TP53 gene), 5637 (high-grade tumor, Grade 2, mutated TP53 gene), and T24 (high-grade tumor, Grade 3, mutated TP53 gene) were treated with several concentrations of silibinin (1, 5, 10, 50, 100, and 150 μM). Cytotoxicity, prooxidant effect, morphological changes, cell migration, cell cycle progression, global methylation profile, and relative expression of HOXB3, c-MYC, PLK1, SMAD4, SRC, HAT, HDAC, and RASSF1A genes were evaluated. The silibinin presented cytotoxic and prooxidant effects in the three cell lines. In mutated TP53 cells, significant interference in cell migration and cell cycle arrest at the G2/M phase was observed. Additionally, silibinin induced global DNA hypomethylation in the highest grade tumor cells. For wild-type TP53 cells, a sub-G1 apoptotic population was present. Furthermore, there was modulation of gene expression responsible for cell growth (SMAD and c-MYC), migration (SRC), cell cycle kinetics (PLK1), angiogenesis (HOXB3), and of genes associated with epigenetic events such as DNA acetylation (HAT) and deacetylation (HDAC). In conclusion, the silibinin inhibited the urinary bladder tumor cell proliferation independently of TP53 status; however, cell cycle effects, gene expression changes, and alteration of cell migration are dependent on TP53 status.Item Toxicogenetic and antiproliferative effects of chrysin in urinary bladder cancer cells.(2020) Lima, Ana Paula Braga; Almeida, Tamires Cunha; Barros, Tatiane Martins Barcelos; Rocha, Lorrana Cachuite Mendes; Garcia, Camila Carrião Machado; Silva, Glenda Nicioli daThe antitumour activity of chrysin have been studied in several types of cancer cells. In urinary bladder cancer, its cytotoxic effects have already demonstrated; however, its mechanism of action is not completely understood and the role of tumour protein p53 (TP53) gene in these effects is unclear. In this study, we investigated the role of chrysin (10, 20, 40, 60 80 and 100 µM) in progression of bladder tumour cells with different status of the TP53 gene and different degrees of tumour (RT4, grade 1, TP53 wild type; 5637, grade 2, TP53 mutated and T24, grade 3, TP53 mutated). Results demonstrated that chrysin inhibited cell proliferation by increasing reactive oxygen species and DNA damage and inhibited cell migration in all cell lines. In TP53 wild-type cells, a sub-G1 apoptotic population was present. In mutated TP53 cells, chrysin caused arrest at the G2/M phase and morphological changes accompanied by downregulation of PLK1, SRC and HOXB3 genes. In addition, in Grade 2 cells, chrysin induced global DNA hypermethylation and, in the highest-grade cells, downregulated c-MYC, FGFR3 and mTOR gene expression. In conclusion, chrysin has antiproliferative and toxicogenetic activity in bladder tumour cells independently of TP53 status; however, the mechanisms of action are dependent on TP53 status.