Multi-targeted effects of G4-aptamers and their antiproliferative activity against cancer cellsстатья
Информация о цитировании статьи получена из
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 20 марта 2018 г.
Аннотация:Available online 5 December 2017
Please cite this article in press as: A.M. Ogloblina, et al., Multi-targeted effects of G4-aptamers and their antiproliferative activity against cancer
cells, Biochimie (2017), https://doi.org/10.1016/j.biochi.2017.11.020
We selected and investigated nine G-quadruplex (G4)-forming aptamers originally designed against different proteins involved in the regulation of cellular proliferation (STAT3, nucleolin, TOP1, SP1, VEGF, and SHP-2) and considered to be potential anticancer agents. We showed that under physiological conditions all the aptamers form stable G4s of different topology. G4 aptamers designed against STAT3, nucleolin and SP1 inhibit STAT3 transcriptional activity in human breast adenocarcinoma MCF-7 cells, and all the aptamers studied inhibit the relaxation of supercoiled DNA by TOP1. STAT3 inhibition by G4 aptamer designed against SP1 protein provides a new explanation for the SP1 and STAT3 crosstalk described recently. We found some correlation between G4-mediated inhibition of the DNA replication and TOP1 activity. The four G4 aptamers from our dataset that appeared to be the strongest TOP1 inhibitors most efficiently decreased de novo DNA synthesis, by up to 79-87%. Seven G4 aptamers demonstrated significantly higher antiproliferative activity on human breast adenocarcinoma MCF-7 cells than on immortalized mammary epithelial MCF-10A cells. Pleiotropic properties of G4 aptamers and their high specificity against cancer cells observed for the majority of the studied G4 aptamers allowed us to present them as promising candidates for multi targeted cancer therapy.