Bovine seminal ribonuclease exerts selective cytotoxicity toward neuroblastoma cells both sensitive and resistant to chemotherapeutic drugs
| Autor: | Jr, Cinatl J., Cinatl J, Kotchetkov R, Matousek J, Bg, Woodcock, Ulrike Koehl, Ju, Vogel, Kornhuber B, Schwabe D |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Cell Survival Antigens CD34 Antineoplastic Agents Hematopoietic Stem Cells Drug Resistance Multiple Kinetics Neuroblastoma Doxorubicin Vincristine Endoribonucleases Tumor Cells Cultured Animals Humans Cattle ATP Binding Cassette Transporter Subfamily B Member 1 Cisplatin Genes MDR Cells Cultured |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0250-7005 |
| Popis: | 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.Human NB 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 NB 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 or in ex vivo expansion culture supplemented with hematopoietic growth factors.In the clonogenic assay it was shown that BS-RNase completely inhibits growth of both parental NB cells and their sublines resistant to chemotherapeutic drugs at concentrations (up to 50 micrograms/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.BS-RNase is a highly efficient agent against NB 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. |
| Databáze: | OpenAIRE |
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