The antiproliferative and antitumor effect of leaf ribonuclease was tested in vitro on the human ML-2 tumor cell line and in vivo on athymic nude mice bearing human melanoma tumors. The antiproliferative activity of this plant ribonuclease in vitro studies was negligible. In the experiments in vivo a significant decrease of the tumor size, however was observed. From nucleases the mung bean nuclease (PhA) was studied first from nucleases. The antitumor effect of this enzyme on ML2 human tumor cell line was almost non-effective. However, significant antitumor activity was detected on human melanoma tumors in vivo. The antitumor effect of black pine pollen nuclease (PN) tested in vitro was also negligible. On the other side, in the experiments in vivo a significant decrease of the human melanoma tumor size was observed too. Recombinant plant nucleases of tomato (TBN1) and hop (HBN1) (submitted to patenting under no. PV 2008-384;Z7585) were isolated to homogeneity and examined for their antitumor effects and cytotoxicity. Although antiproliferative effects of both recombinant nucleases were not significant on the ML-2 cell culture in vitro, the nucleases were strongly cytostatic in vivo after their administration intravenously as stabilized conjugates with polyethylene glycol (PEG). Recombinant both nucleases were as effective against human melanoma tumors as previously studied pine pollen (PN) and mung bean nucleases and their effects were reached at about ten times lower concentrations compared to the use of bovine seminal RNase (BS-RNase).
- MeSH
- endonukleasy farmakologie terapeutické užití MeSH
- lidé MeSH
- melanom farmakoterapie patologie MeSH
- myši nahé MeSH
- myši MeSH
- proliferace buněk účinky léků MeSH
- ribonukleasy farmakologie terapeutické užití MeSH
- rostlinné proteiny farmakologie terapeutické užití MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Recombinant plant nucleases R-TBN1 and R-HBN1 were isolated to homogeneity and examined for their antitumor effects and cytotoxicity. Although antiproliferative effects of both recombinant nucleases were not significant on the ML-2 cell culture in vitro, the nucleases were strongly cytostatic in vivo after their administration intravenously as stabilized conjugates with polyethylene glycol (PEG). Recombinant nucleases were as effective against melanoma tumors as previously studied pine pollen (PN) and mung bean nucleases and their effects were reached at about 10 times lower concentrations compared to the use of bovine seminal RNase (BS-RNase). Because the recombinant nucleases R-HBN1 and R-TBN1 share only 67.4% amino acid identity and showed only partial immunochemical cross-reactivity, their similar anticancerogenic effects can be mainly explained by their catalytical similarity. Both recombinant nucleases showed lower degree of aspermatogenesis compared to BS-RNAse and PN nuclease. Unlike BS-RNase, aspermatogenesis induced by both recombinant nucleases could not be prevented by the homologous antibody complexes. Owing to relatively low cytotoxicity on the one hand, and high efficiency at low protein levels on the other, recombinant plant nucleases R-HBN1 and R-TBN1 appear to be stable biochemical agents that can be targeted as potential antitumor cytostatics.
- MeSH
- antitumorózní látky farmakologie MeSH
- endonukleasy farmakologie genetika MeSH
- glykosylace MeSH
- Humulus enzymologie MeSH
- lidé MeSH
- melanom enzymologie patologie prevence a kontrola MeSH
- myeloidní leukemie enzymologie patologie prevence a kontrola MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- proliferace buněk MeSH
- rekombinantní proteiny farmakologie genetika MeSH
- skot MeSH
- Solanum lycopersicum enzymologie MeSH
- spermatogeneze MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
