Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis.

  • Authors:
    • J Cinatl
    • R Kotchetkov
    • J U Vogel
    • B G Woodcock
    • J Matousek
    • P Pouckova
    • B Kornhuber
  • View Affiliations

  • Published online on: November 1, 1999     https://doi.org/10.3892/ijo.15.5.1001
  • Pages: 1001-1010
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Abstract

Bovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with specific antitumor activity. The cytotoxic action of this agent was examined in human neuroblastoma (NB) cell lines (SK-N-SH and UKF-NB-4) possessing the multidrug resistance (MDR) phenotype and NB cell lines (IMR-32, UKF-NB-1, UKF-NB-2 and UKF-NB-3) without MDR. Although MDR cells expressed large amounts of mdr-1 mRNA, contained functional P-glycoprotein and had 20- to 105-fold lower sensitivities to doxorubicin and vincristine than cells with non-MDR phenotypes, BS-RNase was equally toxic to all NB cells at concentrations employed (0.2 to 100 microg/ml). BS-RNase showed high selectivity for NB cells and was non-toxic to normal fibroblasts and epithelial cells. Ultrastructural investigation and annexin V assay showed that BS-RNase is a powerful inductor of apoptosis. The antitumoral effects of BS-RNase were also demonstrated in vivo using established subcutaneous xenografts in athymic (nude) mice of the MDR-1-bearing UKF-NB-4 cell line. Intratumoral injections (12.5 mg/kg) of BS-RNase over four weeks resulted in complete tumor regression and absence of tumor regrowth over a two-week observation period after cessation of treatment. The results show that BS-RNase selectively kills NB cells by inducing apoptosis and that this agent is active against mdr-1 expressing cells both in vitro and in vivo. BS-RNase fulfills important criteria for a candidate antitumor agent in NB patients with advanced disease.

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Nov 1999
Volume 15 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Cinatl J, Kotchetkov R, Vogel J, Woodcock B, Matousek J, Pouckova P and Kornhuber B: Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis.. Int J Oncol 15: 1001-1010, 1999
APA
Cinatl, J., Kotchetkov, R., Vogel, J., Woodcock, B., Matousek, J., Pouckova, P., & Kornhuber, B. (1999). Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis.. International Journal of Oncology, 15, 1001-1010. https://doi.org/10.3892/ijo.15.5.1001
MLA
Cinatl, J., Kotchetkov, R., Vogel, J., Woodcock, B., Matousek, J., Pouckova, P., Kornhuber, B."Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis.". International Journal of Oncology 15.5 (1999): 1001-1010.
Chicago
Cinatl, J., Kotchetkov, R., Vogel, J., Woodcock, B., Matousek, J., Pouckova, P., Kornhuber, B."Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis.". International Journal of Oncology 15, no. 5 (1999): 1001-1010. https://doi.org/10.3892/ijo.15.5.1001