Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5562626 | Toxicology in Vitro | 2017 | 9 Pages |
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.
Keywords
BH3 mimeticsABT-737RESHBSSγ-H2AXBcl-2-like protein 11Annexin V-FITCTMREBcl-2bcl-wFDAB-cell lymphoma extra-largeBcl-xLMMPataxia telangiectasia mutatedDMSODNA damageBaxBADT-ALLtetramethylrhodamine ethyl ester perchlorateApoptosisATMBcl-2 homology domainfluorescein diacetateDimethyl sulfoxideResveratrolB-cell lymphoma 2T-cell acute lymphoblastic leukemiaHank's balanced salt solutionBIMBcl-2-associated death promoterMitochondrial membrane potentialBcl-2-associated X proteinPropidium iodideBAK
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Authors
MaÅgorzata Opydo-Chanek, Agnieszka Rak, Agnieszka Cierniak, Lidia Mazur,