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Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing

  • Authors:
    • Qi Zhang
    • Shanshan Wang
    • Dexuan Yang
    • Kevin Pan
    • Linna Li
    • Shoujun Yuan
  • View Affiliations / Copyright

    Affiliations: School of Graduate Studies, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China, Jiangsu Asieris Pharmaceuticals Co., Ltd., Taizhou, Jiangsu 225300, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3265-3272
    |
    Published online on: March 29, 2016
       https://doi.org/10.3892/ol.2016.4380
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Abstract

The established urinary antibiotic nitroxoline has recently regained considerable attention, due to its potent activities in inhibiting angiogenesis, inducing apoptosis and blocking cancer cell invasion. These features make nitroxoline an excellent candidate for anticancer drug repurposing. To rapidly advance nitroxoline repurposing into clinical trials, the present study performed systemic preclinical pharmacodynamic evaluation of its anticancer activity, including a methyl thiazolyl tetrazolium assay in vitro and an orthotopic urological tumor assay in vivo. The current study determined that nitroxoline exhibits dose‑dependent anti‑cancer activity in vitro and in urological tumor orthotopic mouse models. In addition, it was demonstrated that the routine nitroxoline administration regimen used for urinary tract infections was effective and sufficient for urological cancer treatment, and 2 to 4‑fold higher doses resulted in obvious enhancement of anticancer efficacy without corresponding increases in toxicity. Furthermore, nitroxoline sulfate, one of the most common metabolites of nitroxoline in the urine, effectively inhibited cancer cell proliferation. This finding increases the feasibility of nitroxoline repurposing for urological cancer treatment. Due to the excellent anticancer activity demonstrated in the present study, and its well‑known safety profile and pharmacokinetic properties, nitroxoline has been approved to enter into a phase II clinical trial in China for non‑muscle invasive bladder cancer treatment (registration no. CTR20131716).
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Copy and paste a formatted citation
Spandidos Publications style
Zhang Q, Wang S, Yang D, Pan K, Li L and Yuan S: Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing. Oncol Lett 11: 3265-3272, 2016.
APA
Zhang, Q., Wang, S., Yang, D., Pan, K., Li, L., & Yuan, S. (2016). Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing. Oncology Letters, 11, 3265-3272. https://doi.org/10.3892/ol.2016.4380
MLA
Zhang, Q., Wang, S., Yang, D., Pan, K., Li, L., Yuan, S."Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing". Oncology Letters 11.5 (2016): 3265-3272.
Chicago
Zhang, Q., Wang, S., Yang, D., Pan, K., Li, L., Yuan, S."Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing". Oncology Letters 11, no. 5 (2016): 3265-3272. https://doi.org/10.3892/ol.2016.4380
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Q, Wang S, Yang D, Pan K, Li L and Yuan S: Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing. Oncol Lett 11: 3265-3272, 2016.
APA
Zhang, Q., Wang, S., Yang, D., Pan, K., Li, L., & Yuan, S. (2016). Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing. Oncology Letters, 11, 3265-3272. https://doi.org/10.3892/ol.2016.4380
MLA
Zhang, Q., Wang, S., Yang, D., Pan, K., Li, L., Yuan, S."Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing". Oncology Letters 11.5 (2016): 3265-3272.
Chicago
Zhang, Q., Wang, S., Yang, D., Pan, K., Li, L., Yuan, S."Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing". Oncology Letters 11, no. 5 (2016): 3265-3272. https://doi.org/10.3892/ol.2016.4380
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