Autor: Perlíková, P.; Rylová, G.; Nauš, P.; Elbert, T.; Tloušťová, E.; Bourderioux, A.; Poštová Slavětínská, L.; Motyka, K.; Doležal, D.; Znojek, P.; Nová, A.; Harvanová, M.; Džubák, P.; Šiller, M.; Hlaváč, J.; Hajdúch, M.; Hocek, M.
Název práce v češtině: 7-(2-Thienyl)-7-Deazaadenosine (AB61), nové účinné cytostatikum s komplexním módem účinku
Název práce v angličtině: 7-(2-Thienyl)-7-Deazaadenosine (AB61), a New Potent Nucleoside Cytostatic with a Complex Mode of Action
Studentská publikace: ne
Klíčová slova v češtině: protinádorové léčivo, nukleosid
Klíčová slova v angličtině: anticancer agent, nucleoside
Abstrakt česky: 7- (2-thienyl) -7-deazaadenosine (AB61) vykazuje nanomolární cytotoxickou aktivitu proti různým nádorových buněčným liniím, ale pouze mírné (mikromolární) aktivity proti normálním fibroblastům.
Abstrakt anglicky: 7-(2-Thienyl)-7-deazaadenosine (AB61) showed nanomolar cytotoxic activities against various cancer cell lines but only mild (micromolar) activities against normal fibroblasts. The selectivity of AB61 was found to be due to inefficient phosphorylation of AB61 in normal fibroblasts. The phosphorylation of AB61 in the leukemic CCRF-CEM cell line proceeds well and it was shown that AB61 is incorporated into both DNA and RNA, preferentially as a ribonucleotide. It was further confirmed that a triphosphate of AB61 is a substrate for both RNA and DNA polymerases in enzymatic assays. Gene expression analysis suggests that AB61 affects DNA damage pathways and protein translation/folding machinery. Indeed, formation of large 53BP1 foci was observed in nuclei of AB61-treated U2OS-GFP-53BP1 cells indicating DNA damage. Random incorporation of AB61 into RNA blocked its translation in an in vitro assay and reduction of reporter protein expression was also observed in mice after 4-hour treatment with AB61. AB61 also significantly reduced tumor volume in mice bearing SK-OV-3, BT-549, and HT-29 xenografts. The results indicate that AB61 is a promising compound with unique mechanism of action and deserves further development as an anticancer agent.
Jazyk v originále: angličtina
Název časopisu: Mol. Cancer. Ther.
Rok: 2016
Svazek (ročník): 15
Číslo časopisu v rámci uvedeného svazku: 5
Strana od-do: 922-937
Impact factor: 5.764
Q1: ne

ISSN časopisu: 1535-7163/1538-8514
Vydavatel: American Association for Cancer Research
Způsob financování: CZ.1.07/2.3.00/30.0041
DOI: 10.1158/1535-7163.MCT-14-0933