Bovine seminal ribonuclease exerts selective cytotoxicity toward neuroblastoma cells both sensitive and resistant to chemotherapeutic drugs

0213245 - UZFG-Y 20003033 RIV GR eng J - Journal Article
Činátl, J. - Činátl, J.jr. - Kotchetkov, R. - Matoušek, Josef - Woodcock, B. G. - KOehl, U. - Vogel, J. U. - Kornhuber, B. - Schwabe, D.
Bovine seminal ribonuclease exerts selective cytotoxicity toward neuroblastoma cells both sensitive and resistant to chemotherapeutic drugs.
Anticancer Research. Roč. 20, - (2000), s. 853-860. ISSN 0250-7005. E-ISSN 1791-7530
R&D Projects: GA ČR GA523/96/1738; GA AV ČR KSK2038602; GA AV ČR KSK2052601
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 1.331, year: 2000

Background. Bovine seminal ribonuclease (BS-RNase) exerts selective cytotoxicity toward different types of tumor cells. In the present study, we tested the effects of BS-RNase on cultured neuroblastoma (NB) cells resistant to chemotherapeutic agents. The selectivity of the antitumoral activity of BS-RNase was evaluated using cultures of CD34(+) hematopoietic stem cells. Materials and Methods Human NE cell lines including IMR-32, UKF-NB-2 and UKF-NB-3 were selected for resistance against vincristine, doxorubicin or cisplatin by exposure to increasing concentrations of the respective drug. The cytotoxicity of the drugs to NE cells was evaluated using a clonogenic assay in a methylcellulose medium. Peripheral blood progenitor cells were obtained from adult healthy donors by positive selection using specific anti-CD34(+) antibodies. The toxicity of BS-RNase to CD34(+) cells was assessed in the direct clonogenic assay using methylcellulose medium of in ex vivo expansion culture supplemented with hematopoietic growth factors. Results. In the clonogenic assay it was shown that BS-RNase completely inhibits growth of both parental NE cells and their sublines resistant to chemotherapeutic drugs at concentrations (up to 50 mu g/ml) which have no significant influence on the growth of colony-forming units, granulocyte macrophage and erythroid burst-forming units. Moreover, BS-RNase had no effect on the ex vivo expansion of total hematopoietic cells or of colony-forming cells from CD34(+) progenitors. Conclusions. BS-RNase is a highly efficient agent against NE cells resistant to chemotherapeutic drugs. The lack of toxicity to hematopoietic progenitor cells suggests that BS-RNase is also likely to have tolerable hematopoietic toxicity.
Permanent Link: http://hdl.handle.net/11104/0108783