title: 2-Deoxy-D-glucose Sensitizes Cancer Cells to Barasertib and Everolimus by ROS-independent Mechanism(s).
abstract: The aim of the present study was to investigate: (i) the possibility of sensitizing cancer cells to anticancer drugs using the redox modulator 2-deoxy-D-glucose (2-DDG); (ii) to find such combinations with synergistic cytotoxic effect; (iii) and to clarify the role of reactive oxygen species (ROS) for induction of apoptosis and cytotoxicity through these combinations. The study covers 15 anticancer drugs--both conventional and new-generation. Four parameters were analyzed simultaneously in Jurkat leukemia cells, treated by drugs or 2-DDG (separately or in combination): cell viability, induction of apoptosis, levels of ROS, and level of protein-carbonyl products. Very well-expressed synergistic cytotoxic effects were found after 48-h treatment of Jurkat cells with 2-DDG in combination with: palbociclib, everolimus, lonafarnib, bortezomib, and barasertib. The synergistic cytotoxic effect of everolimus with 2-DDG was accompanied by very strong induction of apoptosis in cells, but a very strong reduction of ROS level. Changes in the levels of protein-carbonyl products were not detected. The synergistic cytotoxic effect of barasertib with 2-DDG was accompanied by very strong induction of apoptosis in cells, without any increase of ROS levels, but with an enhancement of protein-carbonyl products.
authors.affiliation: Medical Faculty, Trakia University, Stara Zagora, Bulgaria Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Zhivko
authors.initials: Z
authors.lastname: Zhelev
authors.affiliation: Medical Faculty, Trakia University, Stara Zagora, Bulgaria.
authors.forename: Donika
authors.initials: D
authors.lastname: Ivanova
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan Medical Faculty, St. Kliment Ohridski Sofia University, Sofia, Bulgaria bakalova@nirs.go.jp.
authors.forename: Rumiana
authors.initials: R
authors.lastname: Bakalova
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000494:pharmacology*; D004357:Drug Synergism; D000068338:Everolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019169:Jurkat Cells; D010755:Organophosphates / Q000008:administration & dosage / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D017382:Reactive Oxygen Species
chemical_list: C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; D010755:Organophosphates; D011799:Quinazolines; D017382:Reactive Oxygen Species; D003847:Deoxyglucose; D000068338:Everolimus
keywords: 2-deoxy-D-glucose; Anticancer drugs; apoptosis; reactive oxygen species; synergism