title: Glutathione may have implications in the design of 3-bromopyruvate treatment protocols for both fungal and algal infections as well as multiple myeloma.
abstract: In different fungal and algal species, the intracellular concentration of reduced glutathione (GSH) correlates closely with their susceptibility to killing by the small molecule alkylating agent 3-bromopyruvate (3BP). Additionally, in the case of Cryptococcus neoformans cells 3BP exhibits a synergistic effect with buthionine sulfoximine (BSO), a known GSH depletion agent. This effect was observed when 3BP and BSO were used together at concentrations respectively of 4-5 and almost 8 times lower than their Minimal Inhibitory Concentration (MIC). Finally, at different concentrations of 3BP (equal to the half-MIC, MIC and double-MIC in a case of fungi, 1 mM and 2.5 mM for microalgae and 25, 50, 100 μM for human multiple myeloma (MM) cells), a significant decrease in GSH concentration is observed inside microorganisms as well as tumor cells. In contrast to the GSH concentration decrease, the presence of 3BP at concentrations corresponding to sub-MIC values or half maximal inhibitory concentration (IC50) clearly results in increasing the expression of genes encoding enzymes involved in the synthesis of GSH in Cryptococcus neoformans and MM cells. Moreover, as shown for the first time in the MM cell model, the drastic decrease in the ATP level and GSH concentration and the increase in the amount of ROS caused by 3BP ultimately results in cell death.
authors: Department of Genetics,Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland.
authors: Katarzyna
authors: K
authors: Niedźwiecka
authors: Department of Genetics,Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland.
authors: Mariusz
authors: M
authors: Dyląg
authors: Department of Pathogen Biology and Immunology, Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland.
authors: Daria
authors: D
authors: Augustyniak
authors: Department of Pathogen Biology and Immunology, Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland.
authors: Grażyna
authors: G
authors: Majkowska-Skrobek
authors: Department of Genetics,Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland.
authors: Magdalena
authors: M
authors: Cal-Bąkowska
authors: KoDiscovery, LLC, UM BioPark, Baltimore, MD, USA.
authors: Young H
authors: YH
authors: Ko
authors: Departments of Biological Chemistry and Oncology and Sidney Kimmel Comprehensive Cancer Center (member at large), Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Peter L
authors: PL
authors: Pedersen
authors: Institut des Sciences de la Vie, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
authors: Andre
authors: A
authors: Goffeau
authors: Department of Genetics,Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland.
authors: Stanisław
authors: S
authors: Ułaszewski
mesh_terms: D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007239:Infections / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology*; D009181:Mycoses / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology*; D011525:Prototheca / Q000472:pathogenicity*; D011773:Pyruvates / Q000494:pharmacology*; D012107:Research Design
chemical_list: D004791:Enzyme Inhibitors; D011773:Pyruvates; C017092:bromopyruvate; D005978:Glutathione
keywords: 3-bromopyruvate (3BP); buthionine sulfoximine; genes expression; glutathione; fungi and MM cells