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Commonly Used Antibiotics Cytotoxic Towards Bladder Cancer Cells

Commonly used oral antibiotics appear to be significantly cytotoxic towards bladder cancer cells, suggesting that their use after transurethral resection of bladder tumours might prevent seeding of cancer cells and thereby decrease recurrence rate.

Ashish M. Kamat, MD, and Donald L. Lamm, MD, with the Department of Urology, at the University of Texas M. D. Anderson Cancer Center, in Houston, Texas, sought to evaluate whether commonly used urinary antimicrobial agents were cytotoxic towards human transitional carcinoma.

According to the researchers, antibiotics such as quinolones, trimethoprim-sulfamethoxazole, cefazolin, and nitrofurantoin represent an attractive choice for prophylaxis after transurethral procedures because they reach high urinary concentrations.

Three human transitional cell carcinoma lines were used: HTB9 (grade 2), T24 (grade 3), and TccSup (grade 4). Each were treated for 96 hours with ciprofloxacin, trimethoprim-sulfamethoxazole, cefazolin, and nitrofurantoin at maximum concentrations of 1000, 1000, 5000, and 2000 µg/mL, respectively.

Cytotoxicity was evaluated using a colorimetric assay, and 6 replicates were performed for each data point.

All 4 antibiotics demonstrated dose-dependent cytotoxicity against the bladder cancer cell lines tested. Significant cytotoxicity (P < .001) was observed, beginning at 12.5 µg/mL (HTB9, TccSup) 50 µg/mL (T24) for ciprofloxacin, 31.25 µg/mL (HTB9, TccSup) and 62.5 µg/mL (T24) for trimethoprim-sulfamethoxazole, 19.5 µg/mL (HTB9) and 156.3 µg/mL (T24, TccSup) for cefazolin, and 7.8 µg/mL (HTB9, T24, TccSup) for nitrofurantoin.

The maximal effect was similar among antibiotics and cytotoxicity was dose dependent for all four antibiotics, the researchers note.

"Our results indicate that these commonly used antibiotics have significant cytotoxicity against bladder cancer cells (grade 2 to 4), producing cell kill rates as great as 95.4%," Dr. Kamat and Dr. Lamm suggest.

"By killing cells that are exfoliated during transurethral bladder tumor resection, antibiotics might decrease the incidence of tumor recurrence and, if proven effective in clinical trials, might obviate intravesical instillation of chemotherapeutic agents," they add.

Urology 2004;63:457-460. "Antitumor activity of common antibiotics against superficial bladder cancer"

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