Genotoxicity and Cytotoxicity of novel 10B carrier ((2R)-4,5,6-trihydroxy-2-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)boronic acid
Journal Title: Medical Science and Discovery - Year 2014, Vol 1, Issue 4
Abstract
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
Authors and Affiliations
Zafer Akan, Hulya Ozdemir, Gokhan Oto, Sabahattin Deniz, Omer Kacar, Ali Sadi Basak, Tahir Cakir, Hatice Uslu Sinav, Goksel Demir
Keywords
Related Articles
- EP ID EP520346
- DOI -
- Views 56
- Downloads 0
Cyberknife re-irradiation for recurrent glioblastoma multiforme
Objective: Treatment of patients with recurrent glioblastoma multiforme (GBM) is challenging. Treatment alternatives include re-operation, chemotherapy and re-irridation. Stereotactic radiosurgery with cyberkn...
Pancreaticoduodenal artery aneurysm: Treatment outcomes of a rare disorder
Objective: Pancreaticoduodenal artery aneurysm is a rare vascular disorder that manifests with a clinical presentation ranging from asymptomatic cases to hemorrhagic shock due to aneurysm rupture. In this st...
Impact of lack of rehabilitation follow-up care on the functional level and autonomy of vascular hemiplegic patients at Kinshasa University clinics on homecoming
Objective: To evaluate the clinical and functional profile of vascular hemiplegia patients when deciding on their return home after hospitalization and evaluate its impact on their caregivers. Material and Me...
The effect of statin use on lens density as assessed by pentacam hr® lens densitometry in adults
Objective: To investigate the association between statin use and cataract development by using Pentacam HR Scheimpflug camera system.Material and Methods: Total 208 age and sex matched participants were included in this...
Examination of preoperative and postoperative levels of rare earth elements (Zn, Cu, Mg, Pb, Mn, Cd, Co and Fe in the blood of ovarian cancer patients
Objective: In this study, serum material drawn preoperatively and postoperatively from totally 33 patients who applied to Department of Gynaecology of Yüzüncü Yıl University Faculty of Medicine and Van Training and Resea...