Ciprofloxacin triggers the apoptosis of human triple-negative breast cancer MDA-MB-231 cells via the p53/Bax/Bcl-2 signaling pathway

  • Authors:
    • Artur Beberok
    • Dorota Wrześniok
    • Jakub Rok
    • Zuzanna Rzepka
    • Michalina Respondek
    • Ewa Buszman
  • View Affiliations

  • Published online on: March 8, 2018     https://doi.org/10.3892/ijo.2018.4310
  • Pages:1727-1737
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Abstract

Fluoroquinolone antibiotics induce cytotoxicity in various cancer cell lines and may therefore represent a potentially important source of novel anticancer agents. The aim of the present study was to examine the effect of ciprofloxacin on the viability, redox balance, apoptosis, expression of p53, Bax and Bcl-2, cell cycle distribution and DNA fragmentation of triple-negative MDA-MB-231 breast cancer cells. The results of the present study demonstrated that ciprofloxacin decreases cell viability in a dose- and time-dependent manner. The half maximal inhibitory concentration values of ciprofloxacin in MDA-MB-231 cells following treatment for 24, 48 and 72 h were 0.83, 0.14 and 0.03 µmol/ml, respectively. Furthermore, it was demonstrated that ciprofloxacin altered the redox signaling pathway, as determined by intracellular glutathione depletion. The results of Annexin V/propidium iodide staining revealed that ciprofloxacin triggered the apoptosis of MDA-MB-231 cells. Furthermore, cipfloxacin treatment stimulated the loss of the mitochondrial transmembrane potential via the Bax/Bcl-2-dependent pathway, thus inducing apoptosis. Ciprofloxacin induced cell cycle arrest at the S-phase; therefore it was hypothesized that ciprofloxacin inhibits topoisomerase II. Oligonucleosomal DNA fragmentation and the elevation of p53 expression were observed in the present study, indicating that this late-apoptotic event may be mediated by the p53-dependent pathway. Therefore, the results of the current study provide important molecular data concerning the cellular cascade, which may explain the cytotoxicity induced by ciprofloxacin in human triple-negative breast cancer cells, thus providing a novel insight into the therapeutic properties of this drug.

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May 2018
Volume 52 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Beberok, A., Wrześniok, D., Rok, J., Rzepka, Z., Respondek, M., & Buszman, E. (2018). Ciprofloxacin triggers the apoptosis of human triple-negative breast cancer MDA-MB-231 cells via the p53/Bax/Bcl-2 signaling pathway. International Journal of Oncology, 52, 1727-1737. https://doi.org/10.3892/ijo.2018.4310
MLA
Beberok, A., Wrześniok, D., Rok, J., Rzepka, Z., Respondek, M., Buszman, E."Ciprofloxacin triggers the apoptosis of human triple-negative breast cancer MDA-MB-231 cells via the p53/Bax/Bcl-2 signaling pathway". International Journal of Oncology 52.5 (2018): 1727-1737.
Chicago
Beberok, A., Wrześniok, D., Rok, J., Rzepka, Z., Respondek, M., Buszman, E."Ciprofloxacin triggers the apoptosis of human triple-negative breast cancer MDA-MB-231 cells via the p53/Bax/Bcl-2 signaling pathway". International Journal of Oncology 52, no. 5 (2018): 1727-1737. https://doi.org/10.3892/ijo.2018.4310