• Investigation of the toxicity of quinolone anticancer drug, levofloxacin, on bone marrow hematopoietic stem cells
  • Azra Rabbani - Chadegani,1,* Melika Zamanian,2
    1. Institute of biochemistry and biophysics at Tehran University
    2. Institute of biochemistry and biophysics at Tehran University


  • Introduction: One of the most common side effects of anticancer drugs is on bone marrow. Disruption on hematopoietic stem cells located in the bone marrow, due to their importance in hematopoiesis, leads to defect in the immune system, blood supply to tissues, and blood clotting. Quinolones are a group of antibiotics studied extensively as anticancer drugs. They can stimulate apoptosis, inhibit cell proliferation and metastasis, hence the use of these drugs as antibiotics or anticancer drugs is associated with several side effects. To date, the effect of levofloxacin on bone marrow has not been studied, therefore, the aim of this study was to investigate the cytotoxic effects of levofloxacin on bone marrow hematopoietic stem cells (HSCs) to determine the appropriate dose of the drug and to identify the mechanism of its action on these cells.
  • Methods: Non-adherent hematopoietic stem cells obtained from male Balb/c mice and cultured in DMEM medium containing 10% FBS in the presence of various concentrations of levofloxacin. Trypan Blue, MTT, Fluorescent staining, Flow cytometry, Western blot and qRT-PCR tests were used in this research.
  • Results: The results showed that the toxicity of levofloxacin on HSCs is dose- and time-dependent in which after 18 h IC50 was 275 µM. Also, fluorescent staining and flow cytometry were indicated that apoptosis increased via increasing toxicity. Content and mRNA expression of HMGB1 protein were decreased by increasing concentration of Levofloxacin, However HMGB1 release into the cell culture media increased suggestively apoptosis has been enhanced. In addition the content and mRNA expression of BCL-2 protein was decreased and content of caspase-3 protein was increased.
  • Conclusion: From the results is concluded that levofloxacin induces apoptosis in HSCs of bone marrow cells through HMGB1 protein and BCL-2, suggesting that it can be employed in alone or combination therapy to minimize anticancer drugs toxicity.
  • Keywords: Levofloxacin, bone marrow hematopoietic stem cells, side effects, cancer, apoptosis.