Ciprofloxacin sensitizes hormone-refractory prostate cancer cell lines to doxorubicin and docetaxel treatment on a schedule-dependent manner
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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.
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.
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.
Ciprofloxacin sensitized HRPC cells to doxorubicin or docetaxel-induced growth inhibition and, therefore, may play a role as chemosensitizing agent in prostate cancer treatment.
KeywordsHRPC Ciprofloxacin Chemosensitization Dose-reduction index Median effect analysis
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).
- 12.Di Lorenzo G, Autorino R, De Laurentiis M, Bianco R, Lauria R, Giordano A, De Sio M, D’Armiento M, Bianco AR, De Placido S (2003) Is there a standard chemotherapeutic regimen for hormone-refractory prostate cancer? Present and future approaches in the management of the disease. Tumori 89(4):349–360PubMedGoogle Scholar
- 14.Elsea SH, McGuirk PR, Gootz TD, Moynihan M, Osheroff N (1993) Drug features that contribute to the activity of quinolones against mammalian topoisomerase II and cultured cells: correlation between enhancement of enzyme-mediated DNA cleavage in vitro and cytotoxic potential. Antimicrob Agents Chemother 37(10):2179–2186PubMedGoogle Scholar
- 30.Naber KG, Sorgel F, Kees F, Jaehde U, Schumacher H (1989) Pharmacokinetics of ciprofloxacin in young (healthy volunteers) and elderly patients, and concentrations in prostatic fluid, seminal fluid, and prostatic adenoma tissue following intravenous administration. Am J Med 87(5A):57S–59SPubMedCrossRefGoogle Scholar