Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives
| Autor: | Ewa Balcerczak, Marta Żebrowska, Karolina Boguszewska, Katarzyna Błaszczak-Świątkiewicz, Maria Świątkowska, Marta Stasiak, Michał Szewczuk |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Benzimidazole Lung Neoplasms Genetic Vectors Apoptosis Pharmacology Transfection Virus 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytotoxic T cell Humans Prodrugs Cytotoxicity RC254-282 bcl-2-Associated X Protein chemistry.chemical_classification Neoplasms. Tumors. Oncology. Including cancer and carcinogens General Medicine Prodrug Cell Hypoxia Gene Expression Regulation Neoplastic 030104 developmental biology Enzyme chemistry A549 Cells 030220 oncology & carcinogenesis Proto-Oncogene Proteins c-bcr Benzimidazoles |
| Zdroj: | Tumor Biology, Vol 39 (2017) |
| ISSN: | 1423-0380 |
| Popis: | Virus-directed enzyme prodrug therapy is one of the major strategy of increasing cytotoxicity of bioreductive agents. This research intended to examine new selected benzimidazole derivatives as a substrate for nitroreductase, the enzyme involved in nitroreduction which is responsible to the production of cytotoxic metabolites. In this way, the selectivity and strength of cytotoxicity can be raised. The effect of benzimidazoles on virus transfected cells and non-virus transfected cells A549 cell line was established by Annexin V + propidium iodide test, western blot, and polymerase chain reaction analysis of specific pro- and anti-apoptotic proteins in the corresponding gene expression and additionally nitroreductase gene expression. Our results proved the pro-apoptotic properties of all tested compounds in normoxia and hypoxia, especially according to virused A549 cells where the time of exposition was reduced from 48 to 4 h. In this shorten period of time, the strongest activity was shown by N-oxide compounds with nitro-groups. The apoptosis was confirmed by generation of BAX gene and protein and reduction of BCL2 gene and protein. |
| Databáze: | OpenAIRE |
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