Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives
Open Access
- 28 July 2017
- journal article
- review article
- Published by IOS Press in Tumor Biology
- Vol. 39 (7)
- https://doi.org/10.1177/1010428317713675
Abstract
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.Keywords
This publication has 20 references indexed in Scilit:
- Phase II Study of the Safety and Antitumor Activity of the Hypoxia-Activated Prodrug TH-302 in Combination With Doxorubicin in Patients With Advanced Soft Tissue SarcomaJournal of Clinical Oncology, 2014
- Targeting hypoxia in the treatment of small cell lung cancerLung Cancer, 2014
- Tirapazamine Sensitizes Hepatocellular Carcinoma Cells to Topoisomerase I Inhibitors via Cooperative Modulation of Hypoxia-Inducible Factor-1αMolecular Cancer Therapeutics, 2014
- Modular adeno-associated virus (rAAV) vectors used for cellular virus-directed enzyme prodrug therapyScientific Reports, 2014
- History of gene therapyGene, 2013
- Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio NanotechnologyInternational Journal of Molecular Sciences, 2012
- Progress and problems with the use of viral vectors for gene therapyNature Reviews Genetics, 2003
- A brief history of gene therapyNature Genetics, 1992
- Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extractionAnalytical Biochemistry, 1987
- Oxygen diffusion and the distribution of cellular radiosensitivity in tumoursThe British Journal of Radiology, 1972