Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives
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 producti...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-07-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317713675 |
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| _version_ | 1849709705106030592 |
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| author | Michał Szewczuk Karolina Boguszewska Marta Żebrowska Ewa Balcerczak Marta Stasiak Maria Świątkowska Katarzyna Błaszczak-Świątkiewicz |
| author_facet | Michał Szewczuk Karolina Boguszewska Marta Żebrowska Ewa Balcerczak Marta Stasiak Maria Świątkowska Katarzyna Błaszczak-Świątkiewicz |
| author_sort | Michał Szewczuk |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1fad81aace6c48c8a1e6aebc2f186d23 |
| institution | DOAJ |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-1fad81aace6c48c8a1e6aebc2f186d232025-08-20T03:15:12ZengSAGE PublishingTumor Biology1423-03802017-07-013910.1177/1010428317713675Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivativesMichał Szewczuk0Karolina Boguszewska1Marta Żebrowska2Ewa Balcerczak3Marta Stasiak4Maria Świątkowska5Katarzyna Błaszczak-Świątkiewicz6Department of Applied Pharmacy, Medical University of Lodz, Lodz, PolandDepartment of Applied Pharmacy, Medical University of Lodz, Lodz, PolandLaboratory of Molecular Diagnostic and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostic, Medical University of Lodz, Lodz, PolandLaboratory of Molecular Diagnostic and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostic, Medical University of Lodz, Lodz, PolandDepartment of Cytobiology and Proteomics, Medical University of Lodz, Lodz, PolandDepartment of Cytobiology and Proteomics, Medical University of Lodz, Lodz, PolandDepartment of Applied Pharmacy, Medical University of Lodz, Lodz, PolandVirus-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.https://doi.org/10.1177/1010428317713675 |
| spellingShingle | Michał Szewczuk Karolina Boguszewska Marta Żebrowska Ewa Balcerczak Marta Stasiak Maria Świątkowska Katarzyna Błaszczak-Świątkiewicz Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives Tumor Biology |
| title | Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives |
| title_full | Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives |
| title_fullStr | Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives |
| title_full_unstemmed | Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives |
| title_short | Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives |
| title_sort | virus directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives |
| url | https://doi.org/10.1177/1010428317713675 |
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