Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status.

Autor: Almeida TC; Programa de Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Guerra CCC; Departamento de Ciências Biológicas (DECBI), Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., De Assis BLG; Programa de Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., de Oliveira Aguiar Soares RD; Laboratório Multiusuário de Citometria de Fluxo, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Garcia CCM; Departamento de Ciências Biológicas (DECBI), Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Programa de Pós-graduação em Ciências Biológicas (CBIOL), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil., Lima AA; 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., da Silva GN; Programa de Pós-graduação em Ciências Farmacêuticas (CIPHARMA), Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.; Programa de Pós-graduação em Ciências Biológicas (CBIOL), 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.
Jazyk: angličtina
Zdroj: Environmental and molecular mutagenesis [Environ Mol Mutagen] 2019 Oct; Vol. 60 (8), pp. 740-751. Date of Electronic Publication: 2019 May 27.
DOI: 10.1002/em.22297
Abstrakt: The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated; however, its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200, and 250 μM) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 5637-grade 2 and T24-grade 3, TP53 mutated). Cell proliferation, clonogenic survival, morphological changes, cell cycle progression, apoptosis rates, genotoxicity, global methylation, immunocytochemistry for p53 and PCNA and relative expression profiles of the AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1, and DNMT1 were evaluated. Resveratrol decreased cell proliferation and induced DNA damage in all cell lines. Regarding the long-term effects, resveratrol reduced the number of colonies in all cell lines; however, TP53 wild type cells were more resistant. Increased rates of apoptosis were found in the TP53 wild type cells and this was accompanied by AKT, mTOR, and SRC downregulation. In addition, the resveratrol antiproliferative effects in wild type TP53 cells were accompanied by modulation of the DNMT1 gene. In the TP53 mutated cells, cell cycle arrest at S phase with PLK1 downregulation was observed. Additionally, there was modulation of the HOXB3/RASSF1A pathway and nuclear PCNA reduction in the highest-grade cells. In conclusion, resveratrol has antiproliferative activity in bladder tumor cells; however, the mechanisms of action are dependent on TP53 status. Environ. Mol. Mutagen., 60:740-751, 2019. © 2019 Wiley Periodicals, Inc.
(© 2019 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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