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

Zafer Akan; Hulya Ozdemir; Gokhan Oto; Sabahattin Deniz; Omer Kacar; Ali Sadi Basak; Tahir Cakir; Hatice Uslu Sinav; Goksel Demir

doi:https://doi.org/10.17546/msd.21367

Makale detayları

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

Yazarlar:

Zafer Akan | Hulya Ozdemir | Gokhan Oto | Sabahattin Deniz | Omer Kacar | Ali Sadi Basak | Tahir Cakir | Hatice Uslu Sinav | Goksel Demir

Yayıncı:

Zafer AKAN

Dergi:

Medical Science and Discovery 2014 Vol.1 Issue 4, pp.96-108

Belge Tipi:

Makale

Yayın Tarihi:

11/2014

Belge Dili:

İngilizce

Document ID (Org No.):

2000827059

Sıklık:

Aylık

eISSN:

2148-6832

pISSN:

2148-6832

DOI:

https://doi.org/10.17546/msd.21367

Özet:

 

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.

Makale detayları

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

Yazarlar: Zafer Akan | Hulya Ozdemir | Gokhan Oto | Sabahattin Deniz | Omer Kacar | Ali Sadi Basak | Tahir Cakir | Hatice Uslu Sinav | Goksel Demir

Yayıncı: Zafer AKAN

Dergi: Medical Science and Discovery 2014 Vol.1 Issue 4, pp.96-108

Belge Tipi: Makale

Yayın Tarihi: 11/2014

Belge Dili: İngilizce

Document ID (Org No.): 2000827059

Sıklık: Aylık

eISSN: 2148-6832

pISSN: 2148-6832

DOI: https://doi.org/10.17546/msd.21367

Sayı

Yazarlar:

Zafer Akan | Hulya Ozdemir | Gokhan Oto | Sabahattin Deniz | Omer Kacar | Ali Sadi Basak | Tahir Cakir | Hatice Uslu Sinav | Goksel Demir

Yayıncı:

Zafer AKAN

Dergi:

Medical Science and Discovery 2014 Vol.1 Issue 4, pp.96-108

Belge Tipi:

Makale

Yayın Tarihi:

11/2014

Belge Dili:

İngilizce

Document ID (Org No.):

2000827059

Sıklık:

Aylık

eISSN:

2148-6832

pISSN:

2148-6832

DOI:

https://doi.org/10.17546/msd.21367