دورية أكاديمية
Inhibition of urinary bladder cancer cell proliferation by silibinin.
العنوان: | Inhibition of urinary bladder cancer cell proliferation by silibinin. |
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المؤلفون: | Barros TMB; Programa de Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Lima APB; Programa de Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Almeida TC; Programa de Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., da Silva GN; Programa de Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Departamento de Análises Clínicas (DEACL), Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Programa de Pós-graduação em Ciência Biológicas (CBIOL), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. |
المصدر: | Environmental and molecular mutagenesis [Environ Mol Mutagen] 2020 Apr; Vol. 61 (4), pp. 445-455. Date of Electronic Publication: 2020 Mar 03. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8800109 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-2280 (Electronic) Linking ISSN: 08936692 NLM ISO Abbreviation: Environ Mol Mutagen Subsets: MEDLINE |
أسماء مطبوعة: | Publication: New York Ny : Wiley-Liss Original Publication: New York, NY : Liss, c1987- |
مواضيع طبية MeSH: | Antineoplastic Agents, Phytogenic/*pharmacology , Cell Proliferation/*drug effects , Silybin/*pharmacology , Urinary Bladder Neoplasms/*drug therapy, Apoptosis/drug effects ; Cell Cycle/drug effects ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Tumor Suppressor Protein p53/genetics ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/pathology |
مستخلص: | Silibinin, 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. © 2020 Wiley Periodicals, Inc. (© 2020 Wiley Periodicals, Inc.) |
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معلومات مُعتمدة: | CNPq-441836/2014-3 International Conselho Nacional de Desenvolvimento Científico e Tecnológico; CBB-APQ-01497-14 International Fundação de Amparo à Pesquisa do Estado de Minas Gerais; 23109.003267/2017-01 International Universidade Federal de Ouro Preto; 23109.003517/2018-85 International Universidade Federal de Ouro Preto |
فهرسة مساهمة: | Keywords: TP53 gene; cell cycle; gene expression; silibinin; urinary bladder cancer |
المشرفين على المادة: | 0 (Antineoplastic Agents, Phytogenic) 0 (Tumor Suppressor Protein p53) 4RKY41TBTF (Silybin) |
تواريخ الأحداث: | Date Created: 20200221 Date Completed: 20201029 Latest Revision: 20201029 |
رمز التحديث: | 20240628 |
DOI: | 10.1002/em.22363 |
PMID: | 32078183 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1098-2280 |
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DOI: | 10.1002/em.22363 |