title: Different effects of two cyclic chalcone analogues on redox status of Jurkat T cells.
abstract: Chalcones are intermediary compounds of the biosynthetic pathway of the naturally flavonoids. Previous studies have demonstrated that chalcones and their conformationally rigid cyclic analogues have tumour cell cytotoxic and chemopreventive effects. It has been shown that equitoxic doses of the two cyclic chalcone analogues (E)-2-(4'-methoxybenzylidene)-(2) and (E)-2-(4'-methylbenzylidene)-1-benzosuberone (3) have different effect on cell cycle progress of the investigated Jurkat cells. It was also found that the compounds affect the cellular thiol status of the treated cells and show intrinsic (non-enzyme-catalyzed) reactivity towards GSH under cell-free conditions. In order to gain new insights into the cytotoxic mechanism of the compounds, effects on the redox status and glutathione level of Jurkat cells were investigated. Detection of intracellular ROS level in Jurkat cells exposed to 2 and 3 was performed using the dichlorofluorescein-assay. Compound 2 did not influence ROS activity either on 1 or 4h exposure; in contrast, chalcone 3 showed to reduce ROS level at both timepoints. The two compounds had different effects on cellular glutathione status as well. Compound 2 significantly increased the oxidized glutathione (GSSG) level showing an interference with the cellular antioxidant defence. On the contrary, chalcone 3 enhanced the reduced glutathione level, indicating enhanced cellular antioxidant activity. To investigate the chalcone-GSH conjugation reactions under cellular conditions, a combination of a RP-HPLC method with electrospray ionization mass spectrometry (ESI-MS) was performed. Chalcone-GSH adducts could not be observed either in the cell supernatant or the cell sediment after deproteinization. The investigations provide further details of dual - cytotoxic and chemopreventive - effects of the cyclic chalcone analogues.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Pécs, P.O. Box 99, H-7602 Pécs, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Rozmer
authors.affiliation: Department of Immunology and Biotechnology, University of Pécs, P.O. Box 99, H-7602 Pécs, Hungary.
authors.forename: Tímea
authors.initials: T
authors.lastname: Berki
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs, P.O. Box 99, H-7602 Pécs, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Maász
authors.affiliation: Department of Pharmaceutical Chemistry, University of Pécs, P.O. Box 99, H-7602 Pécs, Hungary. Electronic address: pal.perjesi@aok.pte.hu.
authors.forename: Pál
authors.initials: P
authors.lastname: Perjési
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D016588:Anticarcinogenic Agents; D047188:Chalcones; D017382:Reactive Oxygen Species; D005978:Glutathione
keywords: Chalcone-glutathione conjugate; Cyclic chalcone analogue; Glutathione; Jurkat cells; ROS