title: Expression of cyclin A in A549 cell line after treatment with arsenic trioxide.
abstract: BACKGROUND
  Arsenic trioxide (ATO) is an effective drug used in acute promyelocytic leukemia (AML). Many reports suggest that ATO can also be applied as an anticancer agent for solid tumors in the future. The influence of arsenic trioxide on the expression of different cell cycle regulators is poorly recognized. The purpose of the current study is to investigate how arsenic trioxide affects cyclin A expression and localization in the A549 cell line.
  
  
  METHODS
  Morphological and ultrastructural changes in A549 cells were observed using light and transmission electron microscopes. Cyclin A localization was determined by immunofluorescence. Image-based cytometry was applied to evaluate the effect of arsenic trioxide on apoptosis and the cell cycle. Expression of cyclin A mRNA was quantified by real-time PCR.
  
  
  RESULTS
  After treatment with arsenic trioxide, increased numbers of cells with cytoplasmic localization of cyclin A were observed. The doses of 10 and 15 μM ATO slightly reduced expression of cyclin A mRNA. The apoptotic phenotype of cells was poorly represented, and the Tali imagebased cytometry analysis showed low percentages of apoptotic cells. The A549 population displayed an enriched fraction of cells in G0/G1 phase in the presence of 5μM ATO, whereas starting from the higher concentrations of the drug, i.e. 10 and 15 μM ATO, the G2/M fraction was on the increase.
  
  
  CONCLUSIONS
  Low expression of cyclin A in the A549 cell line may constitute a potential factor determining arsenic trioxide resistance. It could be hypothesized that the observed alterations in cyclin A expression/distribution may correlate well with changes in cell cycle regulation in our model, which in turn determines the outcome of the treatment.
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Faculty of Medicine, Karlowicza 24, 85-092 Bydgoszcz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Żuryń
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Faculty of Medicine, Karlowicza 24, 85-092 Bydgoszcz, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Krajewski
authors.affiliation: Plant Breeding and Acclimatization Institute - National Research Institute, Bydgoszcz Research Center, Department of Genetics and Breeding of Root Crops, Laboratory of Biotechnology, Powstanców 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, Faculty of Medicine, Karlowicza 24, 85-092 Bydgoszcz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Klimaszewska-Wiśniewska
authors.affiliation: Department of Histology and Embryology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Faculty of Medicine, Karlowicza 24, 85-092 Bydgoszcz, Poland.
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*; D002460:Cell Line; D019925:Cyclin A / Q000187:drug effects / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D019044:Image Cytometry; D008854:Microscopy, Electron; D010087:Oxides / Q000494:pharmacology*
chemical_list: D001152:Arsenicals; D019925:Cyclin A; D010087:Oxides; D000077237:Arsenic Trioxide