Inhibition of urinary bladder cancer cell proliferation by silibinin.

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dc.contributor.authorBarros, Tatiane Martins Barcelos
dc.contributor.authorLima, Ana Paula Braga
dc.contributor.authorAlmeida, Tamires Cunha
dc.contributor.authorSilva, Glenda Nicioli da
dc.date.accessioned2021-09-13T18:45:15Z
dc.date.available2021-09-13T18:45:15Z
dc.date.issued2020pt_BR
dc.description.abstractSilibinin, 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.pt_BR
dc.identifier.citationBARROS, T. M. B. et al. Inhibition of urinary bladder cancer cell proliferation by silibinin. Environmental and Molecular Mutagenesis, v. 61, p. 445-455, 2020. Disponível em: <https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22363>. Acesso em: 10 jun. 2021.pt_BR
dc.identifier.doihttps://doi.org/10.1002/em.22363pt_BR
dc.identifier.issn1098-2280
dc.identifier.urihttp://www.repositorio.ufop.br/jspui/handle/123456789/13705
dc.identifier.uri2https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22363pt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.subjectGene expressionpt_BR
dc.subjectTP53 genept_BR
dc.titleInhibition of urinary bladder cancer cell proliferation by silibinin.pt_BR
dc.typeArtigo publicado em periodicopt_BR
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