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Ciprofloxacin sensitizes hormone-refractory prostate cancer cell lines to doxorubicin and docetaxel treatment on a schedule-dependent manner

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Abstract

Purpose

Combination therapy has generated a significant interest in the clinical setting since certain agents, with known mechanisms of action and non-overlapping toxicities may increase the therapeutic potential of anticancer drugs by decreasing systemic toxicity and overcoming drug resistance. Doxorubicin and docetaxel, two standard antineoplastic agents in hormone-refractory prostate cancer (HRPC) therapy and ciprofloxacin were evaluated singly and in several simultaneous and sequential drug combination schemes, against PC-3 and LNCaP cell lines.

Methods

Cellular viability was determined by the resazurin assay and the assessment of synergism, additivity or antagonism was carried out by the median effect analysis. The importance of dose, exposure time and type of administration were investigated and compared.

Results

Ciprofloxacin–doxorubicin or docetaxel combinations resulted in prominent additive or synergistic effects in both cell lines, when the cells were pre-treated with ciprofloxacin. These results suggest a rationale for dose reduction of doxorubicin and docetaxel in prostate cancer therapy, since the doses needed to achieve 50% cell death may be decreased by approximately 4- to 15-fold or 3- to 8-fold, respectively, after a pre-treatment with ciprofloxacin. In contrast, the referred combinations yielded moderate antagonistic effects when used concurrently in this in vitro system.

Conclusions

Ciprofloxacin sensitized HRPC cells to doxorubicin or docetaxel-induced growth inhibition and, therefore, may play a role as chemosensitizing agent in prostate cancer treatment.

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Acknowledgments

This work was supported by a grant (SFRH/BDE/15519/2004) from Foundation for Science and Technology (FCT) (Portugal) and from Bluepharma, Pharmaceutical Industry SA (Portugal).

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

    Ana Catarina Pinto, João Nuno Moreira & Sérgio Simões

  2. Bluepharma, Pharmaceutical Industry SA, S. Martinho do Bispo, Coimbra, Portugal

    Ana Catarina Pinto & Sérgio Simões

  3. Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    João Nuno Moreira & Sérgio Simões

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  1. Ana Catarina Pinto
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  2. João Nuno Moreira
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Correspondence to Sérgio Simões.

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Pinto, A.C., Moreira, J.N. & Simões, S. Ciprofloxacin sensitizes hormone-refractory prostate cancer cell lines to doxorubicin and docetaxel treatment on a schedule-dependent manner. Cancer Chemother Pharmacol 64, 445–454 (2009). https://doi.org/10.1007/s00280-008-0892-6

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  • DOI: https://doi.org/10.1007/s00280-008-0892-6

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