title: Combination of ABT-737 and resveratrol enhances DNA damage and apoptosis in human T-cell acute lymphoblastic leukemia MOLT-4 cells.
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.
authors.affiliation: Department of Experimental Hematology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, Poland. Electronic address: malgorzata.opydo-chanek@uj.edu.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Opydo-Chanek
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rak
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Cierniak
authors.affiliation: Department of Experimental Hematology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Mazur
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004249:DNA Damage; D004357:Drug Synergism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009596:Nitrophenols / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C501332:ABT-737; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D009596:Nitrophenols; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D013449:Sulfonamides; D016159:Tumor Suppressor Protein p53; D000077185:Resveratrol
keywords: ABT-737; Apoptosis; BH3 mimetics; DNA damage; Resveratrol; T-ALL