Genotoxicity and Cytotoxicity of novel 10B carrier ((2R)-4,5,6-trihydroxy-2-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)boronic acid

Öz

Objective: Although surgery and chemotherapy have been greatly successful in the treatment of many types of tumors, these treatment modalities have some limitations. In particular, the side effects of conventional radiotherapy warrant the development of new therapy methods, such as Boron Neutron Capture Therapy (BNCT). In the present study, the cytotoxic and genotoxic properties of novel synthesized boron carrier, ((2R)-4,5,6-trihydroxy-2-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)boronic acid (10BDG), and the apoptotic pathways triggered by 10BDG were examined. Material and Methods: As it defined previously, 10BDG was complexed through a low-high pH reaction and was tested using a Fournier Transform InfraRed-Attenuated Total Reflectance (FT-IR/ATR) spectrophotometer. The cytotoxicity of 10BDG was tested through the MTT assay. The detection of caspases 3, 8, and 9 was performed to determine the activated apoptotic pathways by 10BDG. The Poly (ADP-Ribose) Polymerase (PARP) cleavage and DNA damage induced by this compound were tested through western blot and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. Results: The average LogIC50 and LogLD50 levels of 10BDG over NCI-H209 cell line were to be found 72.1±10 ug/ml and 171.8±25 mg/kg, respectively. Caspase-9 activation, caspase-3 activation, PARP cleavage, and caspase-3-dependent DNA fragmentation were observed. The genotoxicity analysis was performed using the plasmid fragmentation assay, which revealed the absence of fragmentation. Conclusion: Bio-distrubition analysis showed that boron content was elevated to 12.63 from 4.44 ppm in the tumor tissue by the 10BDG injections. In epitome, 10BDG exhibit slight cytotoxic but no genotoxic properties. Based on the antiproliferative properties of 10BDG, in addition to acting as an adjuvant in cancer radiotherapy and chemotherapy, this compound appears to be an alternative boron carrier for BNCT

Anahtar Kelimeler

• ((2R)-4,5,6-trihydroxy-2-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)boronic, 10BDG, Apoptosis, Genotoxicity, Cancer, BNCT, MAT-LyLu, Biodistribution

Genotoxicity and Cytotoxicity of novel 10B carrier ((2R)-4,5,6-trihydroxy-2- (hydroxymethyl)tetrahydro-2H-pyran-3-yl)boronic acid

Öz

Kaynakça

1. Moss GP, Smith PAS, Tavernier D. Glossary of class
2. names of organic compounds and reactivity intermediates
3. based on structure (IUPAC Recommendations 1995). Pure
4. Umano M, Uechi K, Uriuda T, Murayama S, Azuma H,
5. Shinohara A, et al. Tumor accumulation of epsilon-poly
6. lysines-based polyamines conjugated with boron clusters.
7. Applied radiation and isotopes : including data,
8. instrumentation and methods for use in agriculture,

9. Kreimann EL, Miura M, Itoiz ME, Heber E, Garavaglia
10. RN, Batistoni D, et al. Biodistribution of a carborane
11. containing porphyrin as a targeting agent for Boron
12. Neutron Capture Therapy of oral cancer in the hamster
13. cheek pouch. Archives of oral biology. 2003;48(3):223- 32.
14. Bialek-Pietras M, Olejniczak AB, Tachikawa S,
15. Nakamura H, Lesnikowski ZJ. Towards new boron carriers
16. metallacarboranes bearing cobalt, iron and chromium and
17. their cholesterol conjugates. Bioorganic & medicinal
18. chemistry. 2013;21(5):1136-42. capture therapy:
19. Gonzalez MJ, Miranda Massari JR, Duconge J, Riordan
20. NH, Ichim T, Quintero-Del-Rio AI, et al. The bio
21. energetic theory of carcinogenesis. Medical hypotheses. 2012;79(4):433-9.
22. Copyright © 2014 The Author(s); This is an open-access article distributed under the terms of the Creative Commons Attribution
23. License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium,
24. provided the original work is properly cited.