Year

2015

Type(s)

Journal Article

Author(s)

Czubatka, Anna and Sarnik, Joanna and Lucent, Del and Blasiak, Janusz and Witczak, Zbigniew J. and Poplawski, Tomasz

Source

Chemico-Biological Interactions, 227: 77—88, 2015

Url

http://www.sciencedirect.com/science/article/pii/S0009279714004086

BibTeX

BibTeX

BibTeX

@article{czubatka_novel_2015, title = {A novel carbohydrate derived compound {FCP}5 causes {DNA} strand breaks and oxidative modifications of {DNA} bases in cancer cells}, volume = {227}, issn = {0009-2797}, url = {http://www.sciencedirect.com/science/article/pii/S0009279714004086}, doi = {10.1016/j.cbi.2014.12.023}, abstract = {1,5-Anhydro-6-deoxy-methane-sulfamido-d-glucitol (FCP5) is a functionalized carbohydrate containing functional groups that render it potentially therapeutically useful. According to our concept of ‘functional carb-pharmacophores’ (FCPs) incorporation of the methanesulfonamido pharmacophore to 1,5 glucitol could create a therapeutically useful compound. Our previous studies revealed that FCP5 was cytotoxic to cancer cells. Therefore, in this work we assessed the cytotoxic mechanisms of FCP5 in four cancer cell lines – HeLa, LoVo, A549 and MCF-7, with particular focus on DNA damage and repair. A broad spectrum of methods, including comet assay with modifications, DNA repair enzyme assay, plasmid relaxation assay, and DNA fragmentation assay, were used. We also checked the potential for FCP5 to induce apoptosis. The results show that FCP5 can induce DNA strand breaks as well as oxidative modifications of DNA bases. DNA lesions induced by FCP5 were not entirely repaired in HeLa cells and DNA repair kinetics differs from other cell lines. Results from molecular docking and plasmid relaxation assay suggest that FCP5 binds to the major groove of DNA with a preference for adenosine–thymine base pair sequences and directly induces DNA strand breaks. Thus, FCP5 may represent a novel lead for the design of new major groove-binding compounds. The results also confirmed the validity of functional carb-pharmacophores as a new source of innovative drugs.}, urldate = {2015-02-26}, journal = {Chemico-Biological Interactions}, author = {Czubatka, Anna and Sarnik, Joanna and Lucent, Del and Blasiak, Janusz and Witczak, Zbigniew J. and Poplawski, Tomasz}, month = feb, year = {2015}, keywords = {DNA Repair, 1,5-Anhydro-6-deoxy-methane-sulfamido-d-glucitol, Functional carb-pharmacophores, Genotoxicity, comet assay, DNA Damage}, pages = {77--88}, file = {ScienceDirect Full Text PDF:C:\Users\Tomasz Poplawski\Zotero\storage\T6SXANGW\Czubatka i in. - 2015 - A novel carbohydrate derived compound FCP5 causes .pdf:application/pdf;ScienceDirect Snapshot:C:\Users\Tomasz Poplawski\Zotero\storage\ERHRSZ5W\S0009279714004086.html:text/html}