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Double short-time exposure to pirarubicin produces higher cytotoxicity against T24 bladder cancer cells

  • Original Article
  • Published:
Journal of Infection and Chemotherapy

Abstract

This study was designed to determine the ideal manner (schedule and duration) of intravesical chemotherapy using pirarubicin (THP). At first, T-24 cancer cells were treated with 50, 100, 150, and 200 μg/ml THP for 10, 30 and 60 min. Following the first exposure, at various intervals (3, 6, 12, and 24 h), a second exposure to THP was performed under the same condition in vitro. The cell viability was measured by XTT assay. Further, the cells were scanned with a laser scanning cytometer (LSC) and DNA histograms were analyzed to evaluate the cell-cycle components. A single exposure of T-24 cells to THP resulted in significantly higher inhibition of cell growth for 30 min with 100 μg/ml and higher concentrations of THP; for example, the cell viability was reduced to 15, 2, and 0% by incubating cells with 100, 150, and 200 μg/ml of THP, respectively, whereas it was 49% with 50 μg/ml THP. Double exposure of T-24 cells to THP resulted in significantly higher inhibition of cell growth than single treatment at all intervals. LSC assay demonstrated a higher sub-G1 peak after double treatment with THP when compared with that after a single treatment. Similar cytotoxic effects following double treatment with THP were observed on other bladder cancer cell lines (UMUC3, TCCSUP, 5637, and 253J cells) in vitro. In conclusion, the double short-term exposure to bladder cancer cells by THP has more remarkable cytotoxic effects than the single exposure in vitro.

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Abbreviations

THP:

Tetrahydropyranyl adriamycin (pirarubicin)

LSC:

Laser scanning cytometer

TURBT:

Transurethral resection of bladder tumor

References

  1. Oosterlinck W, Lobel B, Jakse G, Malmström PU, Stöckle M, Strenberg C. Guidelines on bladder cancer. Eur Urol. 2002;41:105–12.

    Article  PubMed  Google Scholar 

  2. Miki T, Nonomura N, Kojima Y, Okuyama A, Nakano E, Kiyohara H, et al. A randomized study on intravesical THP (THP) chemoprophylaxis of recurrence after transurethral resection of superficial bladder cancer. Hinyokika Kiyo. 1997;43:907–12.

    CAS  PubMed  Google Scholar 

  3. Lutzeyer W, Rubben H, Dahm H. Prognostic parameters in superficial bladder cancer: an analysis of 315 cases. J Urol. 1982;127:250–2.

    CAS  PubMed  Google Scholar 

  4. Lamm DL, Torti FM. Bladder cancer, 1996. CA Cancer J Clin. 1996;46:93–112.

    Article  CAS  PubMed  Google Scholar 

  5. Soloway MS, Sofer M, Vaidya A. Contemporary management of stage T1 transitional cell carcinoma of the bladder. J Urol. 2002;167:1573–83.

    Article  PubMed  Google Scholar 

  6. Sylvester RJ, van der MA, Lamm DL. Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol. 2002;168:1964–70.

    Article  CAS  PubMed  Google Scholar 

  7. Lee C, Park MS. Prophylactic treatment of superficial bladder tumor. Int J Urol. 1998;5:511–20.

    Article  CAS  PubMed  Google Scholar 

  8. Nilsson S, Ragnhammar P, Glimelius B, Nygren P. A systematic overview of chemotherapy effects in urothelial bladder cancer. Acta Oncol. 2001;40:371–90.

    Article  CAS  PubMed  Google Scholar 

  9. Brausi M, Collette L, Kurth K, van der Meijden AP, Oosterlinck W, Witjes JA, et al. Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: a combined analysis of seven EORTC studies. Eur Urol. 2002;41:523–31.

    Article  PubMed  Google Scholar 

  10. Hinotsu S, Akaza H, Ohashi Y, Kotake T. Intravesical chemotherapy for maximum prophylaxis of new early phase superficial bladder carcinoma treated by transurethral resection: a combined analysis of trials by the Japanese Urological Cancer Research Group using smoothed hazard function. Cancer. 1999;86:1818–26.

    Article  CAS  PubMed  Google Scholar 

  11. Matsumura Y. Cooperative study of therapy of superficial bladder cancer by intravesical instillation of pirarubicin. Am J Clin Oncol. 1990;13(suppl 1):S5–10.

    Article  PubMed  Google Scholar 

  12. Yamamoto Y, Nasu Y, Saika T, Akaeda T, Tsushima T, Kumon H. The absorption of pirarubicin instilled intravesically immediately after transurethral resection of superficial bladder cancer. BJU Int. 2000;86:802–4.

    Article  CAS  PubMed  Google Scholar 

  13. Fukushima T, Ueda T, Nakamura T. Pharmacokinetics and action mechanism of anthracyclines. Gan To Kagaku Ryoho. 1992;19:445–50.

    CAS  PubMed  Google Scholar 

  14. Akaza H, Niijima T, Hisamatsu T, Fujigaki M, et al. Comparative investigation on use of (2″R)-4′-O-tetrahydropyranyl-adriamycin and adriamycin as intravesical chemotherapy for superficial bladder tumors. Urology. 1988;32:141–5.

    Article  CAS  PubMed  Google Scholar 

  15. Sylvester RJ, Oosterlinck W, Witjes JA. The schedule and duration of intravesical chemotherapy in patients with non-muscle-invasive bladder cancer: a systematic review of the published results of randomized clinical trials. Eur Urol. 2008;53:709–19.

    Article  CAS  PubMed  Google Scholar 

  16. Maier S, Reich E, Martin R, Bachem M, Altug V, Hautmann RE, et al. Tributyrin induces differentiation, growth arrest and apoptosis in androgen-sensitive and androgen-resistant human prostate cancer cell lines. Int J Cancer. 2000;88:245–51.

    Article  CAS  PubMed  Google Scholar 

  17. Heney NM, Ahmed S, Flanagan MJ, Frable W, Corder MP, Hafermann MD, et al. Superficial bladder cancer: progression and recurrence. J Urol. 1983;130:1083–6.

    CAS  PubMed  Google Scholar 

  18. Pode D, Alon Y, Horowitz AT, Vlodavsky I, Biran S. The mechanism of human bladder tumor implantation in an in vitro model. J Urol. 1986;136:482–6.

    CAS  PubMed  Google Scholar 

  19. Fitzpatrick JM, West AB, Butler MR, Lane V, O’Flynn JD, et al. Superficial bladder tumors (stage pTa, grades 1 and 2): the importance of recurrence pattern following initial resection. J Urol. 1986;135:920–2.

    CAS  PubMed  Google Scholar 

  20. Soloway MS, Masters S. Urothelial susceptibility to tumor cell implantation: influence of cauterization. Cancer. 1980;46:1158–63.

    Article  CAS  PubMed  Google Scholar 

  21. Sugano O, Hatakeyama T, Kato H. Investigation of retention time of intravesical instillation therapy with pirarubicin (THP). Gan To Kagaku Ryoho. 1996;23:1169–74.

    CAS  PubMed  Google Scholar 

  22. Takamoto S, Ota K. Flow cytometric analysis of the effect of THP-adriamycin on the cell cycle traverse of RPMI-8402 cells: comparison with adriamycin. Gan To Kagaku Ryoho. 1986;13:1868–75.

    CAS  PubMed  Google Scholar 

  23. Tanaka M, Yoshida S, Kimura K. Mechanism of inhibition of DNA polymerases by 4′-epiadriamycin and 4′-O-tetrahydropyranyladriamycin. Gann. 1983;74:829–36.

    CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Ms. Chihiro Sato and Ms. Akiko Kawara-Yamazaki for technical assistance.

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Authors and Affiliations

  1. Department of Urology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Takuo Maruyama, Yoshihide Higuchi, Toru Suzuki, Jun Qiu, Shingo Yamamoto & Hiroki Shima

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  1. Takuo Maruyama
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  2. Yoshihide Higuchi
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  3. Toru Suzuki
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  4. Jun Qiu
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  5. Shingo Yamamoto
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  6. Hiroki Shima
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Corresponding author

Correspondence to Shingo Yamamoto.

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Maruyama, T., Higuchi, Y., Suzuki, T. et al. Double short-time exposure to pirarubicin produces higher cytotoxicity against T24 bladder cancer cells. J Infect Chemother 17, 11–16 (2011). https://doi.org/10.1007/s10156-010-0088-y

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  • DOI: https://doi.org/10.1007/s10156-010-0088-y

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