title: The influence of arsenic trioxide on the cell cycle, apoptosis and expression of cyclin D1 in the Jurkat cell line.
abstract: Cyclin D1 drives cell cycle progression at the G1/S transition and is believed to play a significant role in tumorigenesis, contributing to efficient proliferation of many cancer cells. Consequently, it is also recognized as an end-point biomarker of therapeutic outcome for different treatment modalities in cancer. In this study we aimed to evaluate the expression and localization of cyclin D1 in arsenic trioxide (ATO) treated Jurkat cells (lymphoblastic leukemia cell line) and to correlate these results with the extent of cell death and/or cell cycle alterations. Jurkat cells were incubated with increasing concentrations of ATO (0.2, 0.6 and 1.0μM) for 24h in standard cell culture conditions. To reach our goal we performed annexin V/PI labeling for detection of cell death and RNase/PI labeling for evaluation of cell cycle distribution, which were followed by the respective flow cytometric analyses of ATO-treated Jurkat cells. Transmission electron microscopy was applied for visualization of the cell ultrastructure. For cyclin D1 estimation a biparametric cyclinD1/cell cycle assay was done and localization of the protein was shown after immuno-labeling using light microscopy (ABC procedure) and confocal fluorescence microscopy. We found that there were no significant changes in the percentages of cyclin D1-positive cells after the treatment with ATO, but at the same time mean fluorescence intensity reflecting cyclin D1 content was gradually increasing along with the cell cycle progression, irrespective of the applied dose of the drug. On the other hand, we found a nuclear-cytoplasmic shift of this protein as a major treatment-related response, which was in good accord with an increased rate of cell death and suggested that cyclin D1 cytoplasmic degradation is an important determinant of the therapeutic efficiency of ATO in the Jurkat cell line.
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Karlowicza 24, 85-092 Bydgoszcz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zuryń
authors.affiliation: Plant Breeding and Acclimatization Institute - National Research Institute Radzikow, Research Division in Bydgoszcz, Department of Genetics and Breeding of Root Crops, Laboratory of Biotechnology, Powstancow Wielkopolskich 10, 85-090 Bydgoszcz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Litwiniec
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Karlowicza 24, 85-092 Bydgoszcz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Gagat
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Karlowicza 24, 85-092 Bydgoszcz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Drzewucka
authors.affiliation: Department of Immunology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Gackowska
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Karlowicza 24, 85-092 Bydgoszcz, Poland. Electronic address: agrzanka@cm.umk.pl.
authors.forename: Alina
authors.initials: A
authors.lastname: Grzanka
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D019938:Cyclin D1 / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D046529:Microscopy, Electron, Transmission; D010087:Oxides / Q000494:pharmacology*
chemical_list: D001152:Arsenicals; D010087:Oxides; D019938:Cyclin D1; D000077237:Arsenic Trioxide
keywords: Arsenic trioxide (ATO); Cell death; Cyclin D1; Jurkat cells