Comparison between synthetic and natural G4-ligands and the effects of their binding to DNA

prezentace, poster

angličtina

Among local and non-canonical DNA structures are G-rich sequences that can form G-quadruplex (G4) sequencees widespread qmong prokaryotic and eukaryotic kingdoms and are an increasingly used targets for regulatory proteins. There are evidence from more than three decades of research confirm their function in important cell processes such as transcription and replication. G4s have become targets for anticancer drugs because of their ligands high specifity and affinity. We focused on the differences between binding of G4-ligands to DNA and their subsequent effect on cells. In the present study, the effects of G4-ligands on tumor (MCF-7) and non-tumor cell lines (HEK293ft) were studied in relation to binding to the DNA and connected mechanisms. Concentration and time-dependent dtudies were performed to study different effects of these compounds. Mentioned cell lines were used to study cell viability after exposure to G4-ligands. Morphological alterations weree observed by fluorescent-based studies as confocal microscopy or ThT assay (Thiflavin T) supplemented by electromobility shift assay (EMSA). Apoptotic and anti-apoptotic genes were studied, and a strong effect derived from the binding of our tested molecules was observed. Our study propose that natural G4-ligands were used preferentially due to their significant lower toxicity to non-tumor cell line, and with the same specifity as designed synthetic ligands, that even at low concentrations cause singificant cell damage. In conclusion, treatment with natural G4-ligands leads to comparable eeffects to what we obtains with synthetic ligands a d holds a great potential as future cardio-oncological therapeutics.

G4-ligands,DNA-binding

PORUBIAKOVÁ, O.; CANTARA, A.; PŘEPECHALOVÁ, V.; BRÁZDA, V.

4. 7. 2021

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