Combination of ABT-737 and resveratrol enhances DNA damage and apoptosis in human T-cell acute lymphoblastic leukemia MOLT-4 cells.
Toxicol In Vitro
; 42: 38-46, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28366708
ABSTRACT
ABT-737 belongs to a new class of anticancer agents named BH3 mimetics. ABT-737 competitively binds to surface hydrophobic grooves of anti-apoptotic proteins of Bcl-2 family, counteracting their protective effect. Resveratrol is a natural polyphenol that has been shown to inhibit the proliferation and/or induce apoptosis in a number of different types of cancer cells. The present study was designed to analyze the combined effects of ABT-737 and resveratrol on human acute lymphoblastic leukemia cells. The in vitro cytotoxic activity of these agents against MOLT-4 leukemia cells was determined using the Coulter electrical impedance method, comet assay, and flow cytometry, light microscopy and western blot techniques. The results are the first data showing that ABT-737 combined with resveratrol markedly decreased the cell viability, increased DNA damage, caused the cell cycle perturbation, and synergistically enhanced apoptosis in MOLT-4 cells, when compared to the data obtained after application of the single agent. Moreover, the simultaneous treatment of leukemia cells with ABT-737 and resveratrol resulted in a reduction in mitochondrial membrane potential, an increase of p53 protein level and up-regulation of the Bax/Bcl-2 ratio. The obtained data indicate that the combination of ABT-737 and resveratrol is a promising approach for acute lymphoblastic leukemia treatment that should be further explored.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
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Sulfonamidas
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Compostos de Bifenilo
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Antineoplásicos
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Nitrofenóis
Limite:
Humans
Idioma:
En
Revista:
Toxicol In Vitro
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article