Ciprofloxacin inhibits proliferation and promotes generation of aneuploidy in Jurkat cells.
Ciprofloxacin is widely used in antimicrobial therapy. However it also inhibits mitochondrial topoisomerase II and therefore affects cellular energy metabolism. At a concentration exceeding 80 microg/ml ciprofloxacin induces apoptosis, while at 25 microg/ml it inhibits proliferation of Jurkat cells without any symptoms of cell death. The aim of this study was to explain the mechanisms of ciprofloxacin-evoked perturbations of the cell cycle. Human lymphoidal cells (Jurkat) were exposed to ciprofloxacin (25 microg/ml) for 4-11 days and effects of the drug on cell proliferation (light microscopy), cell cycle (flow cytometry), cell size and morphology (confocal microscopy) as well as number of chromosomes (chromosomal spread analysis) were investigated. Exposition of Jurkat cells to ciprofloxacin inhibited cell proliferation,increased proportion of cells in the G2/M-phase of the cell cycle, compromised formation of the mitotic spindle and induced aneuploidy. These observations indicate that ciprofloxacin applied at concentrations insufficient for induction of apoptosis may stop cell proliferation by inhibition of mitosis. Chromosomal instability of such cells may, at least potentially, increase a risk of cancer development.
Koziel
R
R
Laboratory of Bioenergetics and Biomembranes, Nencki Institute of Experimental Biology, Warsaw, Poland.
Szczepanowska
J
J
Magalska
A
A
Piwocka
K
K
Duszynski
J
J
Zablocki
K
K
D024422:Aneugens / Q000494:pharmacology; D000782:Aneuploidy; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000473:pathology; D018613:Microscopy, Confocal; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism
D024422:Aneugens; D000890:Anti-Infective Agents; D002939:Ciprofloxacin